169,857 research outputs found
Cytoprotective function of sAPPa in human keratinocytes
No full textAKT; Amyloid precursor protein; Apoptosis; Cell adhesion; Cytoprotection; Staurosporine; UV-B sAPPa, the soluble form of the b-amyloid precursor protein, has been shown to act as a potent epidermal growth factor by stimulating keratinocyte proliferation and migration. In this report we provide evidence for a cytoprotective role of sAPPa. As a model we used HaCaT cells and normal human keratinocytes (NHK) cultured in the absence of fetal calf serum and bovine pituitary extract. Under these conditions keratinocytes began to undergo apoptosis at increasing rates after 96 h of culture. Surprisingly, keratinocytes were protected from apoptosis by the addition of 50 nM recombinant sAPPa. Subsequent experiments were performed to elucidate the regulatory basis of the cytoprotective role of sAPPa. We found that recombinant sAPPa facilitated the substrate adhesion of keratinocytes in the first 30 minutes after seeding. The basis for this adhesion-promoting function was shown by the ability of recombinant sAPPa to continuously coat the culture dish thereby promoting the ability to bind keratinocytes. A second mechanism explaining the cytoprotective role was found in the significant inhibition of apoptosis by recombinant sAPPa. In HaCaT cells moderate UV-B irradiation was sufficient to induce apoptosis. In contrast, induction of apoptosis in NHK required additionally the depletion of endogenous sAPPa suggesting that sAPPa mediates protection against UV-B irradiation. Staurosporine-induced apoptosis rates were significantly reduced by about 59% after addition of recombinant sAPPa. These results show that sAPPa exerts a pronounced cytoprotective effect and that this effect is mediated by facilitated cell adhesion and by the antiapoptotic function of sAPPa. Abbreviations. APP Amyloid precursor protein ± NHK Normal human keratinocytes ± PKC Protein kinase C ± sAPPa Soluble form of AP
Arsenic contamination in groundwater system of Viterbo area (Central Italy)
No full textIn the last years the presence of arsenic in groundwater became an urgent environmental issue. The As maximum concentration in
drinking water has been changed from 50 μg/l to 10 μg/l, mainly due the effect observed on populations exposed to drinking water
rich in arsenic. Since many springs and wells of the Cimino-Vicano area exceeds the limits provided by Council Directive 98/83/EC,
arsenic has become the most urgent issue of local governments bodies. The aim of this paper is to investigate about the presence of this
element in groundwater and to contribute understanding of the behaviour of this in aquatic environment. In this project have been
analyzed 44 waters samples, with temperatures ranging from 15° C to 62° C, and they have been compared with data obtained
from paper of Sappa et al., 2014 [1], relative to water supply network. The results show that the predominant specie of As in
agricultural and thermal water in reducing conditions is arsenite As (III) while the predominant
Geochemical modeling and multivariate statistical evaluation of trace elements in arsenic contaminated groundwater systems of Viterbo Area, (Central Italy)
No full textContamination of groundwater by naturally occurring arsenic has recently become a disturbing environmental problem in Viterbo area, Central Italy. Arsenic concentrations in most of the public supply networks exceed the maximum allowable limit of 10 μg/l (WHO) for drinking water. The primary purpose of this paper is to obtain a better understanding of the factors contributing to the high levels of As in water supply networks. This study focuses on (a) the determination of basic hydrochemical characteristics of groundwater, (b) the identification of the major sources and processes controlling the As contamination in public supply networks, (c) to find out possible relationships among the As and other trace elements through principal component analysis (PCA). Groundwater samples from public water supply wells and springs were collected and analysed for physico-chemical parameters and trace elements. Springs and well water samples are predominantly of the Na-HCO3, Na -Ca-HCO3 and Ca-HCO3 types and the highest arsenic concentrations were observed in Na-HCO3 type water. Eh-pH diagrams reveal that H2AsO4 - and HAsO4 2-, As(V) arsenate, are the dominating As species highlighting slightly to moderately oxidizing conditions. Geochemical modeling indicates that arsenic-bearing phases were undersaturated in the groundwater, however most of the samples were saturated with respect to Fe (i.e. magnetite, hematite and goethite) and Al (diaspore and boehmite) oxide and hydroxide minerals. Concentrations of As, Li, B, Co, Sr, Mo, U and Se are highly correlated (r > 0.7) with each other, however in some groundwater samples As show also good correlations (r > 0.5) with Fe and Mn elements reflecting the relationships among the trace elements result from different geochemical processes. Evaluation of the principal component (PCA) analysis and geochemical modeling suggest that the occurrence of As and other trace element concentrations in groundwater are probably derived from (i) weathering and/or dissolution of volcanic source aquifer materials and (ii) adsorption/desorption processes on the Fe and Al oxide and hydroxide minerals. © 2014 Sappa et al.; licensee Springer
Holo-APP and G-protein-mediated signaling are required for sAPPa-induced activation of the Akt survival pathway
No full textInternational audienceAccumulating evidence indicates that loss of physiologic amyloid precursor protein (APP) function leads to reduced neuronal plasticity, diminished synaptic signaling and enhanced susceptibility of neurons to cellular stress during brain aging. Here we investigated the neuroprotective function of the soluble APP ectodomain sAPPa (soluble APPa), which is generated by cleavage of APP by a-secretase along the non-amyloidogenic pathway. Recombinant sAPPa protected primary hippocampal neurons and SH-SY5Y neuroblastoma cells from cell death induced by trophic factor deprivation. We show that this protective effect is abrogated in neurons from APP-knockout animals and APP-depleted SH-SY5Y cells, but not in APP-like protein 1-and 2-(APLP1 and APLP2) depleted cells, indicating that expression of membrane-bound holo-APP is required for sAPPa-dependent neuroprotection. Trophic factor deprivation diminished the activity of the Akt survival pathway. Strikingly, both recombinant sAPPa and the APP-E1 domain were able to stimulate Akt activity in wild-type (wt) fibroblasts, SH-SY5Y cells and neurons, but failed to rescue in APP-deficient neurons or fibroblasts. The ADAM10 (a disintegrin and metalloproteinase domain-containing protein 10) inhibitor GI254023X exacerbated neuron death in organotypic (hippocampal) slice cultures of wt mice subjected to trophic factor and glucose deprivation. This cell death-enhancing effect of GI254023X could be completely rescued by applying exogenous sAPPa. Interestingly, sAPPa-dependent Akt induction was unaffected in neurons of APP-DCT15 mice that lack the C-terminal YENPTY motif of the APP intracellular region. In contrast, sAPPa-dependent rescue of Akt activation was completely abolished in APP mutant cells lacking the G-protein interaction motif located in the APP C-terminus and by blocking G-protein-dependent signaling with pertussis toxin. Collectively, our data provide new mechanistic insights into the physiologic role of APP in antagonizing neurotoxic stress: they suggest that cell surface APP mediates sAPPa-induced neuroprotection via G-protein-coupled activation of the Akt pathway
AFFITOPE induced Antibodies spare APP and sAPPa.
No full text<p>Mice were s.c. injected 3 times at a 2-week interval with AD01-, AD02- or Aß1-6-conjugate vaccines adjuvanted with ALUM. Plasma was taken at sacrification. A-D depict controls for full length APP-specific FACS analysis using the APP-specific mAb mP2-1 (A-C) or naïve plasma (D); E and F show two exemplaric analyses of AD02 and Aß1-6 induced plasma in this assay. G and H depict analysis of immune responses against sAPPa following vaccination (n = 10 animals/treatment group) by peptide ELISA. For analysis of the presence of APP specific antibodies, the % of cells shifting in the non-APP expressing population and the % of cells shifting in the presence of the secondary antibody only were subtracted from the % of APP-positive cells shifting as indicator of APP binding. The assay threshold was set to 5%. Positive controls (A-C) show an Ab dose dependent (LOD of ≤1ng/ml mAb) shift of the APP positive but not of the APP-negative population. No reactivity was seen with plasma from naïve animals (D). AD02-induced samples show no reactivity to the APP-positive as well as APP-negative populations (E) whereas Aß1-6 induced sera show a specific shift at a dilution of 1/200 in the APP-positive cell population (upper right quadrant) with only very limited reactivity to the non-APP expressing cell population (lower and upper left quadrant; F). Neither AD01 nor AD02 was found to elicit sAPPa-specific Abs (G). On the contrary, following Aß1-6 immunization, sera of all 10 animals were shown to cross-react with sAPPa (G). A correlation analysis for anti Aß1-42 and anti sAPPa reactivity of plasma samples from animals undergoing Aß1-6 immunization (H) fails to detect a significant correlation indicating a highly individual response against sAPPa (Pearson r = 0.1534; R²= 0.02354); Titers determined were calculated based on ODmax/2 values. aAPP…anti APP specific Ab, neg.contr… is secondary Ab only; AD01, AD02 is AD01- and AD02-vaccine induced plasma, Aß1-6 is Aß1-6 vaccine induced plasma, sec.only… secondary Ab only, pos. control…. mAb P2-1</p
Analysis of the effect that different parameters in the SAPPA model have on its anticipation tendency.
No full text(A) Illustration of what the asynchrony between the SAPPA model and the external sinusoidal stimulus can look like, and how it’s measured. (B-F) Analysis of the anticipation as a function of D and τ in Eq (5), and A in Eq (7): (B) A = 0, (C) A = -1.0, (D) A = -0.5, (E) A = 0.5, (F) A = 1. In these analyses (B-F) the parameter f = 1. The numbers in each cell indicate the anticipation (in ms) observed when the SAPPA model synchronized with the external sinusoidal stimulus. A black cell indicates that the SAPPA model did not synchronize with the external sinusoidal stimulus and hence the asynchronies could not be computed. In the analyses (B-F), the asynchrony quickly moves away from zero as 0 τ D = 1. Additionally, we explored how different initial conditions affect the model’s asynchrony and discontinuities, described in the Supplementary S2 Fig which contains the bifurcation diagram for the SAPPA model when D = 1.</p
Surface organometallic chemistry: reaction of alkyne vapours with Ru3(CO)12 supported on inorganic oxides
No full textTrinuclear clusters of Ruthenium and Osmium: compounds containing M-C bonds to heteroatom ligands
No full text
KELOMPOK KERJA GURU (KKG) DALAM UPAYA MENINGKATKAN KUALITAS BELAJAR SISWA PADA MTs. PADANG SAPPA KECAMATAN PONRANG KABUPATEN LUWU
No full textABSTRAK
Risma, 2011. “Kelompok Kerja Guru (KKG) dalam Upaya Meningkatkan Kualitas
Belajar Siswa pada MTs. Padang Sappa Kecamatan Ponrang Kabupaten
Luwu”. Skripsi Program Studi Pendidikan Agama Islam, Jurusan Tarbiyah
Sekolah Tinggi Agama Islam Negeri (STAIN) Palopo Pembimbing (I) Drs. H.
Fahmi Damang, M.A. dan Pembimbing (II) Drs. Efendi P., M.Sos.I.
Kata Kunci: Kelompok Kerja Guru (KKG), Kualitas Belajar Siswa
Skripsi ini membahas tentang Kelompok Kerja Guru (KKG) dalam upaya
meningkatkan kualitas belajar siswa pada MTs. Padang Sappa, di mana penelitian ini
mengangkat permasalahan tentang 1). Peranan Kelompok Kerja Guru dalam upaya
meningkatkan kualitas belajar siswa di MTs. Padang Sappa. 2). Korelasi antara
Kelompok Kerja Guru terhadap kualitas belajar siswa di MTs. Padang Sappa, dan 3.
Kendala dan upaya dalam meningkatkan kualitas belajar siswa di MTs. Padang
Sappa.
Penelitian ini menggunakan teknik pengumpulan data digunakan untuk
mengumpulkan berbagai macam alternatif jawaban dari objek dikaji, yakni a).
Observasi, atau pengamatan langsung di lapangan, b). Interview yaitu metode
pengumpulan data dengan cara wawancara atau tanya jawab, c). Kuisioner (angket)
adalah suatu teknik pengumpulan data dengan cara mengisi suatu daftar yang
berisikan rangkaian pertanyaan, kemudian selanjutnya keseluruhan data tersebut
dianalisis secara kualitatif dengan menggunakan tabel-tabel sederhana kemudian hasil
olahan tersebut dijadikan acuan dasar untuk menganalisa secara kualitatif terhadap
suatu permasalahan telah dirumuskan sebelumnya dan memberikan gambaran tentang
Kelompok Kerja Guru (KKG) terhadap kualitas belajar siswa dan hasil analisis
berbentuk tabel frekuensi dan persentase.
Hasil penelitian ini dapat menentukan usaha untuk meningkatkan kualitas
belajar siswa di sini peran guru sebagai kulminator terpadu dengan peran sebagai
evaluator mampu memancing aspirasi siswa, mampu mengaktifkan siswa dalam
proses belajar mengajar, mampu memvariasi pengelolaan kelas, mampu melayani
perbedaan individu siswa, serta mampu meningkatkan interaksi belajar siswa. Usaha�usaha dilakukan guru pendidikan agama Islam di MTs. Padang Sappa Kec. Ponrang
Kab. Luwu dalam meningkatkan kualitas pendidikan agama Islam adalah a). Pola
pengajaran efektif, b). Pelaksanakan metode pengajaran, c). Pengadaan les mata
pelajaran, d). Keaktifan guru dalam mengajarkan mata pelajaran PAI, e). Penguasaan
guru pada materi pelajaran diajarkan
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