Miracle-dz/UniFAR-FTUs huggingface dataset:
Interactome Analysis Reveals Ezrin Can Adopt Multiple Conformational States*

Background: Ezrin is a conformationally regulated microfilament-membrane linker restricted to the apical aspect of epithelial cells. Results: Quantitative mass spectrometry identified proteins that associate with different ezrin conformations; the interactors include novel apical microvilli-associated proteins, with classes perceiving ezrin's conformation differentially. Conclusion: Different proteins selectively associate with three distinct conformational states of ezrin. Significance: This study extends the conformational activation model of ezrin and identifies new interacting partners. Ezrin, a member of the ezrin-radixin-moesin family (ERM), is an essential regulator of the structure of microvilli on the apical aspect of epithelial cells. Ezrin provides a linkage between membrane-associated proteins and F-actin, oscillating between active/open and inactive/closed states, and is regulated in part by phosphorylation of a C-terminal threonine. In the open state, ezrin can bind a number of ligands, but in the closed state the ligand-binding sites are inaccessible. In vitro analysis has proposed that there may be a third hyperactivated form of ezrin. To gain a better understanding of ezrin, we conducted an unbiased proteomic analysis of ezrin-binding proteins in an epithelial cell line, Jeg-3. We refined our list of interactors by comparing the interactomes using quantitative mass spectrometry between wild-type ezrin, closed ezrin, open ezrin, and hyperactivated ezrin. The analysis reveals several novel interactors confirmed by their localization to microvilli, as well as a significant class of proteins that bind closed ezrin. Taken together, the data indicate that ezrin can exist in three different conformational states, and different ligands “perceive” ezrin conformational states differently.
Natural history of celiac disease autoimmunity in a USA cohort followed since 1974

Abstract Background. The natural history and the possible changes of celiac disease (CD) prevalence over time are still unclear. Objectives. 1) To establish whether loss of tolerance to gluten may occur at any age; 2) to investigate possible changes of CD prevalence over time; and 3) to investigate CD-related co-morbidities. Methods. We analyzed 3,511 subjects with matched samples from 1974 (CLUE I) and 1989 (CLUE II). To avoid a selection bias regarding survival, we also screened 840 CLUE I participants who deceased after the 1974 survey. Outcome measure. CD autoimmunity (positivity to auto-antibodies) over time. Results. CD autoimmunity was detected in seven subjects in 1974 (prevalence 1:501) and in an additional nine subjects in 1989 (prevalence 1:219). Two cases of CD autoimmunity were found among the 840 subjects deceased after CLUE I. Compared to controls, untreated CD subjects showed increased incidence of osteoporosis and associated autoimmune disorders, but they did not reach statistical significance. Conclusions. During a 15-year period CD prevalence increased 2-fold in the CLUE cohort and 5-fold overall in the US since 1974. The CLUE study demonstrated that this increase was due to an increasing number of subjects that lost the immunological tolerance to gluten in their adulthood.
A scanning electron microscopic study of the developing epithelial scleral papillae in the eye of the embryonic chick

Eyes of early embryonic chicks possess 14 scleral papillae, derived from the conjuctival epithelium and present as transient structures between seven and 11 days of incubation. These papillae induce the formation of the 14 scleral ossicles, which develop in the adjacent, neural crest‐derived ectomesenchyme. Each papilla undergoes a predictable series of developmental changes, divided by Murrary ('43) into six morphological stages (M stages 1–6). We have confirmed his staging, and provide a scanning electron microscopic (SEM) evaluation of papilla development. The earliest stage that can be visualized with the S.E. M. is M stage 2. We describe the initial modifications of the surface of papilla cells, the presence of large microvilli and the asymmetrical morphogenesis and growth of the papillae. Papillae are shed by a mechanism that involves elongation of the cells at the base of the papilla. Such moribund papillae consist of necrotic cells coated with fibers.
Prevalence and clinical associations of lupus anticoagulant, anticardiolipin antibodies, and anti-beta2-glycoprotein I antibodies in patients with systemic lupus erythematosus.

BACKGROUND The presence of antiphospholipid antibodies (aPLs) is associated with the clinical features of antiphospholipid syndrome (APS), which comprises venous and arterial thrombosis and pregnancy loss, and systemic lupus erythematosus (SLE). The prevalence of aPLs has been reported to be different in patient populations affected by either of these conditions. We performed a retrospective study to evaluate the prevalence and clinical associations of aPLs, including lupus anticoagulant (LAC), anticardiolipin (aCL), and anti-beta2-glycoprotein I antibodies (anti-beta2-GPI) in a cohort of Korean patients with SLE. METHODS This study included samples from 88 SLE patients for whom aPL testing had been advised between June 2006 and July 2009 at the Dong-A University Hospital. Serum and plasma samples were tested for LAC, aCL (IgG, IgM), and anti-beta2-GPI (IgG, IgM) antibodies. Clinical data from patients were obtained from a review of medical records. RESULTS LAC was the most common (34.1% of total patients, 30/88) antibody, followed by IgM aCL (31.8%, 28/88), IgG aCL (18.2%, 16/88), and IgM and IgG anti-beta2-GPI (both 5.7%, 5/88 each). Positivity for LAC was strongly associated with venous/arterial thrombosis (P=0.002). CONCLUSIONS LAC was the most common antibody detected in Korean SLE patients and is shown to have a significant association with the presence of venous/arterial thrombosis. The measurement of LAC may be clinically useful in identifying patients with SLE who are at a high risk for venous/arterial thrombosis.
A comparison of brachial artery row‐mediated vasodilation using upper and lower arm arterial occlusion in subjects with and without coronary risk factors

Background: The ultrasound assessment of brachial artery flow‐mediated vasodilation provides a noninvasive means for measuring endothelial function. The test is performed using either upper or lower arm blood pressure cuff arterial occlusion to induce hyperemia. Upper arm occlusion produces a greater hyperemic stimulus. Brachial artery flow‐mediated vasodilation is abnormal in the presence of coronary risk factors.
Effects of Regular Switching between Languages during Random Number Generation

Random number generation is a task that engages working memory and executive processes within the domain of number representation. In the present study we address the role of language in number processing by switching languages during random number generation (numbers 1–9), using German (L1) and English (L2), and alternating L1/L2. Results indicate large correspondence between performance in L1 and L2. In contrast to nonswitching performance, randomization with alternating languages showed a significant increase of omitted responses, whereas the random sequences were less stereotyped, showing significantly less repetition avoidance and cycling behavior. During an intentional switch between languages, errors in language sequence appeared in 23% of responses on the average, independently of the quality of randomization but associated with a clear persistence of L2. These results indicate that random number generation is more closely linked to auditory-phonological representation of numerals than to visual arabic notation.
Blood pressure, hypertension, RAAS blockade, and drug therapy in diabetic kidney disease.

Type 2 diabetes is the most common cause of CKD and ESRD in the United States and the Western world. Hypertension is prevalent in this cohort, and control of blood pressure is perhaps the most important risk factor to reduce CKD progression. The most recent blood pressure target recommended by the Kidney Disease: Improving Global Outcomes and Kidney Disease Outcomes Quality Initiative guideline committees is less than 140/90 mmHg for all patients with CKD. There is some evidence for those with 1 g or more of albuminuria, albeit weak, to support a blood pressure target of less than 130/80 mmHg. Multiple studies demonstrate that renin-angiotensin-aldosterone system (RAAS) blockers are important in reducing cardiovascular risk and progression of CKD in those with advanced proteinuric nephropathy. However, there is no evidence that they prevent nephropathy or that reduction in microalbuminuria alone is associated with slowed nephropathy progression. The purpose of this article is to review the major studies that have evaluated cardiovascular and kidney endpoints in patients with diabetes and the role of RAAS blockers in the treatment of this disease.
İlköğretim 7.Sınıf Matematik Öğretiminde Aktif Öğrenmenin Öğrenci Başarısı Üzerine Etkisi

Ogrencilerin matematigi sevmesi ve basarili olabilmesi icin ogretimde degisiklikler yapmak ve yeni ogretme ve ogrenme modellerine yonelmek gerekmektedir. Bu calismada, Aktif Ogrenmenin ogrenci basarisi uzerindeki etkisi belirlenmeye calisilmistir. Bu amacla ogrenciler ile uygulama yapilarak konu ile ilgili veriler derlenmis ve analiz edilmistir. Balikesir ilinin Dursunbey ilcesinde merkeze bagli Sabahattin Gondur Ilkogretim Okulu'ndaki 7. Sinif ogrencilerine (ndeney=20, nkontrol=22, ntoplam=42) "cember ve daire" konusunun aktif ogrenme yontemleri ve geleneksel yontemler kullanarak ogretimi yapilmis ve bu iki yontemin ogrencilerin basarisina etkisi incelenmistir. Deney grubu ogrencilerine Aktif Ogrenme Yaklasimina uygun etkinliklerle ("pi sayisi ve cemberin cevresi", "dairenin alani") ve kontrol grubu ogrencilerine geleneksel yontemler kullanilarak ogretim yapilmistir. Uygulamadan once olcme araci olarak gruplara ontest verilmistir. Uygulama bitiminde gruplara sontest uygulanmistir. Aktif ogrenme yontemlerinin geleneksel yontemlere gore ogrencilerin basarisinda daha etkili oldugu sonucuna varilmistir. Deney grubu ogrencilerinin aktif ogrenme yontemlerinin uygulanmasindan once ve sonra matematik basarilarinda geleneksel yontemlerin uygulandigi kontrol grubuna gore anlamli bir fark gozlenmistir.
Detection of lymph node metastases in pediatric and adolescent/young adult sarcoma: Sentinel lymph node biopsy versus fludeoxyglucose positron emission tomography imaging—A prospective trial

Lymph node metastases are an important cause of treatment failure for pediatric and adolescent/young adult (AYA) sarcoma patients. Nodal sampling is recommended for certain sarcoma subtypes that have a predilection for lymphatic spread. Sentinel lymph node biopsy (SLNB) may improve the diagnostic yield of nodal sampling, particularly when single‐photon emission computed tomography/computed tomography (SPECT‐CT) is used to facilitate anatomic localization. Functional imaging with positron emission tomography/computed tomography (PET‐CT) is increasingly used for sarcoma staging and is a less invasive alternative to SLNB. To assess the utility of these 2 staging methods, this study prospectively compared SLNB plus SPECT‐CT with PET‐CT for the identification of nodal metastases in pediatric and AYA patients.
Carcinoma of the cervix in elderly patients treated with radiotherapy: patterns of care and treatment outcomes

Objective The aim of this analysis was to examine the management of cervix cancer in elderly patients referred for radiotherapy and the results of treatment in terms of overall survival (OS), relapse-free survival (RFS), and treatment-related toxicities. Methods Patients were eligible if they were aged ≥75 years, newly diagnosed with cervix cancer and referred for radiotherapy as part of their treatment. Patient details were retrieved from the gynaecology service database where clinical, histopathological treatment and follow-up data were prospectively collected. Results From 1998 to 2010, 126 patients aged ≥75 years, met selection criteria. Median age was 81.5 years. Eighty-one patients had definitive radiotherapy, 10 received adjuvant radiotherapy and 35 had palliative radiotherapy. Seventy-one percent of patients had the International Federation of Gynecology and Obstetrics stage 1b–2b disease. Median follow-up was 37 months. OS and RFS at 3 years among those treated with curative intent were 66.6% and 75.9% respectively with majority of patients dying without any evidence of cervix cancer. Grade 2 or more late toxicities were: bladder 5%, bowel 11%, and vagina 27%. Eastern Cooperative Oncology Group (ECOG) status was a significant predictor of OS and RFS with each unit increment in ECOG score increased the risk of death by 1.69 times (p<0.001). Conclusion Following appropriate patient selection, elderly patients treated curatively with radiotherapy for cervix cancer have good disease control. Palliative hypofractionated regimens are well tolerated in patients unsuitable for radical treatment.
Activin A, B, and AB increase human trophoblast cell invasion by up-regulating N-cadherin.

CONTEXT Inhibin β-subunits and activin receptors are expressed by human trophoblast cells. Although activin A has been shown to enhance human trophoblast cell invasion, whether two additional activin isoforms, activin B and AB, exert similar effects remains unknown. Moreover, whether the expression of mesenchymal adhesion molecule neural cadherin (N-cadherin) is essential for this proinvasive effect of activin has yet to be determined. OBJECTIVE To examine the effects of all three activin isoforms on human trophoblast cell invasion and the involvement of N-cadherin. DESIGN HTR8/SVneo immortalized extravillous cytotrophoblast cells and primary cultures of human extravillous cytotrophoblast cells were used as study models. Small interfering RNA-mediated knockdown approaches were used to investigate the molecular determinants of activin-mediated functions. SETTING An academic research center. MAIN OUTCOME MEASURES Reverse transcription-quantitative real-time PCR and Western blot analysis were used to examine mRNA and protein levels, respectively. Cell invasiveness was assessed by Matrigel-coated transwell assays. RESULTS All three activin isoforms produced comparable increases in HTR8/SVneo cell invasion as well as N-cadherin expression. In addition, the up-regulatory effect of activin isoforms on N-cadherin was confirmed in primary cultures of human trophoblast cells. Interestingly, small interfering RNA-mediated down-regulation of N-cadherin attenuated basal and activin-induced invasion of both HTR8/SVneo and primary trophoblast cells. All three activin isoforms induced equivalent phosphorylation of SMAD2 and SMAD3. Importantly, activin-stimulated cell invasion, up-regulation of N-cadherin, as well as activation of SMAD2/SMAD3 were abolished by the TGF-β type I receptor inhibitor SB431542 in HTR8/SVneo cells. Furthermore, knockdown of SMAD2/3 or common SMAD4 abolished the stimulatory effects of all three activin isoforms on N-cadherin expression. CONCLUSION Activin A, B, and AB produce comparable increases in human trophoblast cell invasion by up-regulating N-cadherin expression in a SMAD2/3-SMAD4-dependent manner.
A Mutation Analysis of the Phenylalanine Hydroxylase (PAH) Gene in the Israeli Population

Hyperphenylalaninemia (HPA) is a group of diseases characterized by a persistent elevation of phenylalanine levels in tissues and biological fluids. The most frequent form is phenylalanine hydroxylase deficiency, causing phenylketonuria (PKU). Among 159 Israeli patients (Jews, Muslim and Christian Arabs and Druze) with HPA, in whom at least one of the mutations was characterized, a total of 43 different mutations were detected, including seven novel ones. PKU was very rare among Ashkenazi Jews and relatively frequent among Jews from Yemen, the Caucasian Mountains, Bukhara and Tunisia. The mutations responsible for the high frequency were: exon3del (Yemenite Jews), L48S (Tunisian Jews) and E178G, P281L and L48S (Jews from the Caucasian Mountains and Bukhara). Among the non‐Jewish Israeli citizens, the disease was relatively frequent in the Negev and in the Nazareth vicinity, and in many localities a unique mutation was detected, often in a single family. While marked genetic heterogeneity was observed in the Arab and Jewish populations, only one mutation A300S, was frequent in all of the communities. Several of the other frequent mutations were shared by the non‐Ashkenazi Jews and Arabs; none were mutual to Ashkenazi Jews and Arabs.
Mucilaginibacter defluvii sp. nov., isolated from a dye wastewater treatment facility.

A non-motile, rod-shaped bacterium, designated strain A5(T), was isolated from a dye wastewater treatment facility in the Republic of Korea. Cells were Gram-reaction-negative, aerobic, catalase-positive and oxidase-negative. The major fatty acids were C(16 : 0), C(18 : 0), iso-C(15 : 0) and summed feature 3 (C16 : 1)ω6c and/or C(16 : 1ω7c) and the major polar lipid was phosphatidylethanolamine. The strain contained MK-7 as the only isoprenoid quinone and the DNA G+C content was 41.2 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain A5(T) forms an evolutionary lineage within the radiation encompassing the members of genus Mucilaginibacter, with Mucilaginibacter lutimaris BR-3(T) as its nearest neighbour (96.6% sequence similarity). A number of phenotypic characteristics distinguished strain A5(T) from the members of the genus Mucilaginibacter. On the basis of the evidence presented in this study, strain A5(T) represents a novel species, for which the name Mucilaginibacter defluvii sp. nov. is proposed. The type strain is A5(T) ( = KCTC 23922(T) = JCM 18283(T)).
Motor Neuron Disease-Associated Mutant Vesicle-Associated Membrane Protein-Associated Protein (VAP) B Recruits Wild-Type VAPs into Endoplasmic Reticulum-Derived Tubular Aggregates

The vesicle-associated membrane protein-associated proteins (VAPs) VAPA and VAPB interact with lipid-binding proteins carrying a short motif containing two phenylalanines in an acidic tract (FFAT motif) and targets them to the cytosolic surface of the endoplasmic reticulum (ER). A genetic mutation (P56S) in the conserved major sperm protein homology domain of VAPB has been linked to motor-neuron degeneration in affected amyotrophic lateral sclerosis (ALS) patients. We report that in the CNS, VAPB is abundant in motor neurons and that the P56S substitution causes aggregation of mutant VAPB in immobile tubular ER clusters, perturbs FFAT-motif binding, and traps endogenous VAP in mutant aggregates. Expression of mutant VAPB or reduction of VAP by short hairpin RNA in primary neurons causes Golgi dispersion and cell death. VAPA and VAPB are reduced in human ALS patients and superoxide dismutase 1 (SOD1)-ALS-transgenic mice, suggesting that VAP family proteins may be involved in the pathogenesis of sporadic and SOD1-linked ALS. Our data support a model in which reduced levels of VAP family proteins result in decreased ER anchoring of lipid-binding proteins and cause motor neuron degeneration.
Analysis of corneal injuries in King Mahendra Memorial Eye Hospital Bharatpur, Chitwan.

OBJECTIVE To determine the corneal injuries pattern. MATERIAL AND METHOD It is a retrospective hospital based analysis of 5504 corneal injuries among the 111781 patients attending King Mahendra Memorial Eye Hospital over a period of 4 years in order to know the lesions pattern for planning purpose. RESULTS Among the corneal lesions, 59.7% were traumatic and 40.3% were non traumatic lesions, wood stick was the commonest traumatic agent (28.7%), 24.1% cases reported in hospital within 7 days of injury. Corneal ulcer was the most commonest traumatic lesions (48.2%). Clinically 69.2% cases were of bacterial lesions. 71.4% cases underwent medical treatment. 54.24% had good vision after treatment 1,2,3,5. CONCLUSION Early treatment with antibiotic drops in a case of corneal injuries restores good vision. Protective glasses while working are the preventive measure against traumatic lesions.
Quantitative studies on the movement of fluid and lymphocytes through periodontal tissue and into the draining lymph

Chronic lymph drainage techniques in sheep have been used to map the pathways and to quantify the fluid and cell traffic through periodontal tissues. The continuous collection of cervical and prescapular lymph has demonstrated that 65% of labelled protein tracer injected into the periodontal tissues could be found in lymph over a period of 7.5 hours. Nearly 90% of the total radioactivity could be accounted for between the lymph and the tissue site. When silk was impregnated with radiolabelled albumin and a tooth ligated, the kinetics of the subsequent appearance of the tracer in lymph emphasized the ease with which macromolecules surrounding the teeth gain access to the lymphatics, regional lymph nodes, and immune apparatus. Animals were primed with BCG and then tuberculin (delayed hypersensitivity) lesions were simultaneously induced in the skin, bowel, and periodontium. When T cells were labelled with radioisotopes and their migration from blood to lymph measured, the periodontal tissue traffic pattern was distinct from the traffic pattern through DTH in the skin and also distinct from the pattern through the small intestine. This indicates that the lymphocyte traffic through the inflamed periodontium has unique features. This tissue specificity was not apparent when lesions were induced with TNFα. The static assessment of lymphocyte subsets within the tissues was also assessed with immunohistochemistry. Microsc. Res. Tech. 56:66–71, 2002. © 2002 Wiley‐Liss, Inc.
Exosome-like Nanoparticles from Intestinal Mucosal Cells Carry Prostaglandin E2 and Suppress Activation of Liver NKT Cells

Regulation and induction of anergy in NKT cells of the liver can inhibit autoimmune and antitumor responses by mechanisms that are poorly understood. We investigated the effects of PGE2, delivered by intestinal, mucus-derived, exosome-like nanoparticles (IDENs), on NKT cells in mice. In this study, we demonstrate that IDENs migrate to the liver where they induce NKT cell anergy. These effects were mediated by an IDENs’ PGE2. Blocking PGE2 synthesis attenuated IDENs inhibition of induction of IFN-γ and IL-4 by α-galactosylceramide (α-GalCer)–stimulated liver NKT cells in a PGE2 E-type prostanoid 2/E-type prostanoid 4 receptor–mediated manner. Proinflammatory conditions enhanced the migration of IDENs to the liver where α-GalCer and PGE2 induced NKT anergy in response to subsequent α-GalCer stimulation. These findings demonstrate that IDENs carrying PGE2 can be transferred from the intestine to the liver, where they act as immune modulators, inducing an anergic-like state of NKT cells. These reagents might be developed as therapeutics for autoimmune liver diseases.
IMPACT OF EDUCATION ON SECURITY PRACTICES IN ICT

Original scientific paper In assuring the security in information technology, user awareness and acquired-user habits are inevitable components, yet they may be qualified as the feeblest ones. As the information technology tries to put its best in providing maximum security, user awareness plays a key-role. Additionally, although the literature provides studies on approaches for teaching information security, there are not many evidences on the impact of education level. Therefore, this study investigates the impact of the education level on user security awareness in using the Information and Communication Technology (ICT) products. For this purpose, a survey was conducted among 433 citizens from different layers of the society. Interestingly, the results indicated that education level has significant impact on all security issues included in the analysis regarding computer usage, web usage and e-mail usage.