1,721,222 research outputs found
An antibody that specifically recognizes a phosphorylated IGF-IR
No full textThe IGF-I receptor (IGF-IR) plays an important role in cell growth control, in malignant transformation, and in cell survival. Its role in human cancer has been firmerly established. High level of IGF-IR in breast cancer is highly correlated with ipsilateral breast tumor recurrence following lumpectomy and radiation therapy. IGF-IR signaling occurs upon activation by its ligands, that induce autophosphorylation of the receptor at several tyrosine residues.. Phosphorylation of tyrosine residue at position 1316 (Y1316) is necessary for tumor formation in nude mice, although not essential for IGF-I-induced mitogenesis.
We generated a rabbit polyclonal antibody that specifically recognizes a phosphorylated IGF-IR. This antibody (anti-pY1316/IGF-IR) do not crossreact with a phosphorylated Insulin receptor, and do not recognizes a C-terminus-truncated IGF-IR nor a mutant IGF-IR having the Y1316 replaced with phenylalanine (Y1316F).
The anti-pY1316/IGF-IR antibody can be used in immunohistchemistry and can be applied for the detection of activated IGF-IRs in human tumor sections. Analyses of Y1316-IGF-IR phosphorylation level are in progress to establish whether this parameter may have a prognostic value in human breast cancer
Mutazione Q283P nel gene HFE in un eterozigote C282Y affetto da emocromatosi.
No full textL’Emocromatosi ereditaria di tipo 1 (HFE1) è una patologia genetica ampiamente diffusa nelle popolazioni caucasiche. Nel Nord Europa si presenta con una frequenza di circa 1/300, mentre in Italia la prevalenza è stimata essere inferiore (1/4000).
Si tratta di una malattia caratterizzata da sovraccarico di ferro nel fegato ed in altri distretti (pancreas, cuore, articolazioni), con iperferritinemia e elevata saturazione della trasferrina serica. Può manifestarsi con cirrosi epatica, diabete, artrite, cardiopatie ed ipogonadismo. La maggior parte dei pazienti affetti da emocromatosi ereditaria presenta un genotipo omozigote per la mutazione C282Y del gene HFE. Alcuni pazienti portatori della mutazione C282Y sono risultati essere eterozigoti composti per altre mutazioni (H63D, S65C, G93R, IVS3+1G>T). In Italia sono riportati molti casi di sovraccarico di ferro in soggetti non omozigoti C282Y, facendo ritenere che altre mutazioni nel gene HFE possano contribuire alla determinazione del fenotipo clinico.
Riportiamo il caso di un soggetto affetto da Emocromatosi lieve, che ad una indagine iniziale è risultato essere eterozigote per la mutazione C282Y. Il sequenziamento dell’intero gene HFE ha evidenziato la presenza di una seconda mutazione missenso 848A>C nell’esone 4, che determina la sostituzione del residuo di glutammina 283 con prolina (Q283P). Nel paziente eterozigote composto analizzato le mutazioni C282Y e Q283P sono risultate essere portate da cromosomi diversi.
Ipotizziamo che la variante Q283P possa ridurre la funzionalità della proteina HFE, probabilmente alterando il sito di legame con la Beta2-microglobulina
A novel mutation of HFE explains the classical phenotype of hereditary hemochromatosis in a C282Y carrier
No full textHereditary hemochromatosis (HH) is the most autosomal recessive disorder in Caucasians, affecting approximately 1 in 300 person. It is characterized by iron overload in many organs, leading to cirrhosis, hepatocellular carcinoma, diabetes, arthritis, heart failure and hypogonadism.
Most of HH patients are homozygous for the C282Y mutations. Some C282Y-carrier patients have been identified to be compound heterozygous for other mutations (H63D, S65C, G93R, IVS3+1G>T, 203delT).
We report a patient with classical HH who is compound heterozygous for C282Y and a novel missense mutation in the exon 4.
This is a 848A>C mutation that causes glutamine to proline substitution at position 283 (Q283P). We hypothesize that the Q283P variant may disrupt the beta2-microglobulin binding site in the HFE protein
Changes in PM10 Composition in Venice Area During Clean and Polluted Periods: a Source Apportionment Study Coupled with SEM-EDS Individual Particle Analysis
Full text linkGenomic organization and expression of the MTHFS gene
No full textThe 5-formyl-tetrahydrololate (5-formyl-THF) is an inhibitor of several folate-dependent enzymes and plays a role in folic acid-dependent one-carbon metabolism. It is synthesized in vivo by the Serine-Hydroxymethyl-Transferase (SHMT), an enzyme expressed at steady level, which activity is inhibited by 5-formyl-THF itself. The 5,10-methenyl-tetrahydrofolate-synthetase (MTHFS) is the only enzyme that metabolize the 5-formyl-THF, catalyzing the ATP-dependent conversion to 5,10-methenyl-THF. The combined activities of MTHFS and SHMT constitute a futile cycle that may buffer the 5-formyl-THF concentration.
The MTHFS is a 28 kDa polypeptide. Its transcripts are detectable in all tissues, but so far no evidence of modulation of its expression has been reported.
The MTHFS gene is located in 15q24.3. It is organized in three exons. The two introns are > 7Kb in length. The gene has no TATA-box, and transcription is initiated at multiple sites at 14-23 nt upstream the translation start codon. Two distinct poly(A) sites have been identified downstream the coding sequence.
The expression kinetics of MTHFS enzyme and transcript has been studied in phytohaemagglutinin (PHA)-activated human lymphocytes. Quiescent cells have low transcription while the enzyme level is relatively high. Upon PHA stimulation the 28 kDa protein level drops down, whereas a 20 kDa isoform is expressed. This smaller isoform is due to the use of an alternative transcription initiation site located 12 nt downstream the major translation start codon, within an initiator element consensus sequence. The role and function of this 20 kDa protein is not known. As the activated lymphocytes enter the cell cycle, the 20 kDa isoform is replaced by the 28 kDa MTHFS enzyme.
This evidence indicates that the MTHFS expression is modulated during the proliferation process,
and this may in turn determine changes in the intracellular 5-formyl-THF level.
Regulating the intracellular level of 5-formyl-THF, the MTHFS activity may influence the methyl-THF concentration and the homocysteine remethylation
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Graphene derived lanthanum carbide targets for the SPES ISOL facility
Full text linkGraphene derived lanthanum carbide targets for the SPES ISOL facility By:Corradetti, S (Corradetti, S.)[ 1 ] ; Carturan, SM (Carturan, S. M.)[ 1,2 ] ; Andrighetto, A (Andrighetto, A.)[ 1 ] ; Mariotto, G (Mariotto, G.)[ 3 ] ; Giarola, M (Giarola, M.)[ 3 ] ; Fabrizi, A (Fabrizi, A.)[ 4 ] ; Maddalena, A (Maddalena, A.)[ 5 ] ; Biasetto, L (Biasetto, L.)[ 1,4 ] CERAMICS INTERNATIONAL Volume: 43 Issue: 14 Pages: 10824-10831 DOI: 10.1016/j.ceramint.2017.05.106 Published: OCT 1 2017 View Journal Impact Abstract Lanthanum carbide based targets were produced as benchmark tests before the production of radioactive uranium carbide targets. Carbides possessing excess carbon and porosity seem to be the best candidates as target for the production of exotic beams in the SPES-ISOL facility. In addition, the capability of tailoring properties such as grains size and pores size represents a step ahead to improve the ions release efficiency. In this work, multilayered graphene was used as source of carbon for the production of LaC and the main physical properties of the produced targets were compared to standard LaCx produced using micrometric graphite. The main output of the work consisted in the reduced total porosity (28.8 vol% vs 47.8 vol%) and increased shrinkage (20.4 vol% vs 5.8 vol%) of the LaCx-Graphene samples compared to LaCx-Graphite ones. This result showed how graphene can be successfully employed as sintering aid for the sintering of carbides. Further studies are ongoing with UO2 as starting reagent for carburization within the project AUL-2013-16-176 "Study of the use of graphene as source of carbon for Uranium Carbide-Graphene nanocomposites production" now under conclusion at the European Commission DG Joint Research Centre - JRC
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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