211,703 research outputs found
Genomic characterization of putative allergen genes in peach/almond and their synteny with apple
No full textAbstract Background Fruits from several species of the Rosaceae family are reported to cause allergic reactions in certain populations. The allergens identified belong to mainly four protein families: pathogenesis related 10 proteins, thaumatin-like proteins, lipid transfer proteins and profilins. These families of putative allergen genes in apple (Mal d 1 to 4) have been mapped on linkage maps and subsequent genetic study on allelic diversity and hypoallergenic traits has been carried out recently. In peach (Prunus persica), these allergen gene families are denoted as Pru p 1 to 4 and for almond (Prunus dulcis)Pru du 1 to 4. Genetic analysis using current molecular tools may be helpful to establish the cause of allergenicity differences observed among different peach cultivars. This study was to characterize putative peach allergen genes for their genomic sequences and linkage map positions, and to compare them with previously characterized homologous genes in apple (Malus domestica). Results Eight Pru p/du 1 genes were identified, four of which were new. All the Pru p/du 1 genes were mapped in a single bin on the top of linkage group 1 (G1). Five Pru p/du 2 genes were mapped on four different linkage groups, two very similar Pru p/du 2.01 genes (A and B) were on G3, Pru p/du 2.02 on G7,Pru p/du 2.03 on G8 and Pru p/du 2.04 on G1. There were differences in the intron and exon structure in these Pru p/du 2 genes and in their amino acid composition. Three Pru p/du 3 genes (3.01–3.03) containing an intron and a mini exon of 10 nt were mapped in a cluster on G6. Two Pru p/du 4 genes (Pru p/du 4.01 and 4.02) were located on G1 and G7, respectively. The Pru p/du 1 cluster on G1 aligned to the Mal d 1 clusters on LG16; Pru p/du 2.01A and B on G3 to Mal d 2.01A and B on LG9; the Pru p/du 3 cluster on G6 to Mal d 3.01 on LG12; Pru p/du 4.01 on G1 to Mal d 4.03 on LG2; and Pru p/du 4.02 on G7 to Mal d 4.02 on LG2. Conclusion A total of 18 putative peach/almond allergen genes have been mapped on five linkage groups. Their positions confirm the high macro-synteny between peach/almond and apple. The insight gained will help to identify key genes causing differences in allergenicity among different cultivars of peach and other Prunus species.</p
Functional role of the overexpression of the myelin and lymphocyte protein MAL in Schwann cells
No full textFor fast propagation of action potentials in the nervous system, higher vertebrates have developed a specialized plasma membrane structure, the myelin, ensheathing nerve fibers. Myelin sheaths are formed by Schwann cells in the peripheral nervous system (PNS), whereas oligodendrocytes are the myelin-forming cells in the central nervous system (CNS). Impairment of the myelin sheath results in severe pathology as seen in multiple sclerosis in the CNS or polyneuropathies such as the Charcot-Marie-Tooth disease in the PNS. During development of peripheral nerves, a coordinated reciprocal signaling between Schwann cells and axons is crucial for accurate Schwann cell development, differentiation as well as maintenance of the myelin sheaths. In addition to orchestrated signal transduction, large amounts of lipids and membrane proteins are synthesized and have to be transported to distinct compartments for proper myelin formation. The transmembrane myelin and lymphocyte protein MAL is associated with lipid rafts, and is important for targeting proteins and lipids to distinct myelin membrane domains. In the PNS, MAL expression starts at around embryonic day 17, implicating a functional role in Schwann cell development. MAL overexpression retards the onset of peripheral myelination, and leads to reduced expression of p75NTR and myelin protein zero (P0). Since accurate expression of p75NTR is essential for proper initiation of myelination, it was suggested that altered p75NTR expression in MAL-overexpressing mice might be the cause of delayed onset of myelination.
To elucidate a functional link between MAL overexpression and retarded myelination, primary mouse Schwann cell cultures were investigated. We could show that the induction of the CREB signaling pathway is functional, indicating that Schwann cells overexpressing MAL are not less responsive to axonal signals. Despite functional activation of the cAMP signaling pathway, significantly reduced mRNA expression levels of P0 and p75NTR were detected in untreated Schwann cells overexpressing MAL. This study revealed that most transcription factors known to modulate P0 expression were not altered in Schwann cells overexpressing MAL. During development, Schwann cells depend on accurate levels of different growth factors. To determine whether the delayed onset of myelination might be caused by a deficient downstream signaling of a particular growth factor, Schwann cells were treated with neuregulin1, nerve growth factor or fibroblast growth factor 1. However, none of the investigated growth factors could ameliorate the reduced expression of P0 and p75NTR in MAL-overexpressing Schwann cells.
MAL-overexpressing Schwann cells were further investigated using a whole genome expression analysis. Most transcripts of genes implicated in Schwann cell development, differentiation and maintenance were not affected by MAL-overexpression. However, we identified a number of genes associated with cytoskeleton organization and components of the basal lamina that are regulated in a MAL-dependent manner. Especially during development and differentiation of Schwann cells, major changes in cellular processes and architecture are crucial for accurate radial sorting and myelination, proposing them as novel candidates for influencing myelination
Tumor targeting of Pt-Mal-LHRH attenuated breast cancer tumor growth.
No full textFemale Balb/c mice were implanted with 4T1 cells (1x106) in the right second mammary fat pad. Tumors were grown for 7 days, distributed into treatment groups, and treated with carbo (carboplatin), or Pt-Mal-LHRH intravenously at varying doses (mg/kg/wk). Tumor volume was measured over 2 wks and Pt-Mal-LHRH doses were found to significantly decrease tumor growth compared to carboplatin and control growth (2A). Pt-Mal-LHRH tumor accumulation was measured by inductively coupled plasma mass spectrometry and found to be significantly higher compared to skeletal muscle (B) and carboplatin (C). Tumor tissue targeting was not found with carboplatin treatment (D). Data is represented as mean ± S.E.M. n = 9 (for each group, A), n = 4 (B-D) * p#p≠ p<0.0001 (5mg/kg Pt-Mal-LHRH compared to ctrl and each carboplatin groups), ⱡ p<0.0001 (10mg/kg Pt-Mal-LHRH compared to ctrl and each carboplatin groups) **** p<0.0001 (20mg/kg Pt-Mal-LHRH compared to ctrl and each carboplatin group).</p
Breast cancer tumor growth is attenuated by Pt-Mal-LHRH treatment.
No full textFemale Balb/c mice were implanted with 4T1 cells (1x106) in the right second mammary fat pad. Tumors were grown for 7 days, distributed into treatment groups, and treated with Pt-Mal-LHRH intravenously at varying doses. Tumor volume was measured every 3 days and Pt-Mal-LHRH treatments (2.5–20mg/kg) showed significant tumor suppression compared to control growth (A). No decrease in body weight was found with Pt-Mal-LHRH treatments (B). Blood was collected by left ventricular puncture and no difference in white blood cells (C), platelets (D), and red blood cell (E) amounts were found between Pt-Mal-LHRH (20mg/kg) treated and control mice (no cancer and cancer groups). Data is represented as mean ± S.E.M. n = 6 (for each group, A-B), n = 3 (C-E) *p<0.05; ****p<0.0001.</p
Pt-Mal-LHRH, a Newly Synthesized Compound Attenuating Breast Cancer Tumor Growth and Metastasis by Targeting Overexpression of the LHRH Receptor
No full textA new
targeting chemotherapeutic agent, Pt-Mal-LHRH, was synthesized
by linking activated cisplatin to luteinizing hormone releasing hormone
(LHRH). The compound’s efficacy and selectivity toward 4T1
breast cancer cells were evaluated. Carboplatin was selected as the
comparative platinum complex, since the Pt-Mal-LHRH malonate linker
chelates platinum in a similar manner to carboplatin. Breast cancer
and normal cell viability were analyzed by an MTT assay comparing
Pt-Mal-LHRH with carboplatin. Cells were also treated with either
Pt-Mal-LHRH or carboplatin to evaluate platinum uptake by ICP-MS and
cell migration using an in vitro scratch–migration assay. Tumor
volume and metastasis were evaluated using an in vivo 4T1 mouse tumor
model. Mice were administered Pt-Mal-LHRH (carboplatin molar equivalent
dosage) through ip injection and compared to those treated with carboplatin
(5 (mg/kg)/week), no treatment, and LHRH plus carboplatin (unbound)
controls. An MTT assay showed a reduction in cell viability (p < 0.01) in 4T1 and MDA-MB-231 breast cancer cells treated
with Pt-Mal-LHRH compared to carboplatin. Pt-Mal-LHRH was confirmed
to be cytotoxic by flow cytometry using a propidium iodide stain.
Pt-Mal-LHRH displayed a 20-fold increase in 4T1 cellular uptake compared
to carboplatin. There was a decrease (p < 0.0001)
in 4T1 cell viability compared to 3T3 normal fibroblast cells. Treatment
with Pt-Mal-LHRH also resulted in a significant decrease in cell-migration
compared to carboplatin. In vivo testing found a significant reduction
in tumor volume (p < 0.05) and metastatic tumor
colonization in the lungs with Pt-Mal-LHRH compared to carboplatin.
There was a slight decrease in lung weight and no difference in liver
weight between treatment groups. Together, our data indicate that
Pt-Mal-LHRH is a more potent and selective chemotherapeutic agent
than untargeted carboplatin
MDA-MB-231 breast cancer tumor growth is attenuated by Pt-Mal-LHRH treatment.
No full textFemale NCr nu/nu mice were implanted with MDA-MB-231 cells (5x106) in the mammary fat pad by Charles River Laboratories. Mice were placed into treatment groups of Pt-Mal-LHRH, carboplatin or saline (ctrl) and treated intravenously with molar equivalent doses of 10mg/kg/wk. Tumor volume was measured over 2 wks and Pt-Mal-LHRH doses were found to significantly decrease tumor growth compared to carboplatin and control growth. Data is represented as mean ± S.E.M. n = 8 (for each group), *p<0.05, ****p<0.0001.</p
Tissue targeting was found with Pt-Mal-LHRH.
No full textTissues were harvested from untreated 12 wk old female Balb/c mice and LHRH receptor protein was analyzed via western blotting. Increased LHRH receptor expression was found in reproductive tissues compared to normal bladder tissue control, with a significant increase found in mammary, uterine and ovarian tissue (A-D). Female Balb/c mice were injected with 20mg/kg by tail vein injection and tissues harvested after 2.5 hrs. Enhanced reproductive tissue accumulation was found with Pt-Mal-LHRH treatment compared to carboplatin (E-G). No difference in brain accumulation was found (H). Data is represented as mean ± S.E.M. n = 3 (A-D); n = 4 (E-H), *p<0.05, **p<0.01, ***p<0.001.</p
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
A lei e o mal estar
No full textDissertação (mestrado) - Universidade Federal de Santa Catarina, Centro de Ciências Jurídicas, Programa de Pós-Graduação em Direito, Florianópolis, 2014.A presente pesquisa busca fazer dialogar o marquês de Sade e Sigmund Freud, para, com base nesta interlocução, pensar na possibilidade de fundar uma ética, a ética da psicanálise tal qual Jacques Lacan constrói no sétimo seminário de seu ensino. Além disso, propusemo-nos a investigar o que esse diálogo tem a dizer sobre os fundamentos do direito moderno cujos principais autores são Hobbes, Locke, Rousseau e Kant. Para isso, por meio de pesquisa de cunho bibliográfico partimos de dois conceitos fundamentais do escritor libertino francês e do psicanalista austríaco: a lei de natureza, de Sade, e a pulsão de morte, de Freud. Ambos os conceitos dizem respeito a um certo empuxo à destruição presente no ser humano, observadas as devidas diferenças entre os autores. O marquês de Sade realiza uma espécie de reinterpretação da teoria contratualista do Estado moderno, elevando seus fundamentos ao absurdo - ou ultrapassando-os - para nos mostrar que esses mesmos alicerces que nos prometem a liberdade, a igualdade e a segurança podem nos levar a um mundo distópico e despótico, operando um retorno ao estado de natureza, o ponto de partida em que cada ser humano é mero objeto à disposição do gozo do outro. Ademais, na leitura de Kant com Sade, perceberemos, junto com Lacan, que a ética kantiana, a apatia que o ser racional deve impor-se para chegar ao Sumo Bem, pode levar justamente ao seu inverso, o mal radical sadiano. Não obstante, ao final, operamos uma inversão: há dois tempos na lei de natureza e na pulsão de morte, o princípio de destruição também pode apontar para uma vontade de criação a partir do nada. Assim, com base na ética da psicanálise, a ética da responsabilidade por nossa posição de sujeitos, resgatamos o imperativo categórico kantiano - agora esvaziado e dialetizado com a ética sadiana - como aquele que manda que ?se faça a lei?, a fim de que a lei encontre um limite, o ponto de basta colocado pela Lei simbólica.Résumé: La présent recherche prétend faire dialoguer le marquis de Sade avec Sigmund Freud a fin de, basée sur cette interlocution, penser à la possibilité de fonder une éthique, l'éthique de la psychanalyse tel quel Jacques Lacan construit dans le septième séminaire de son enseignement. De plus, nous envisageons d'investiguer ce que ce dialogue peut nous pointer sur les fondements du droit moderne, dont les auteurs principaux sont Hobbes, Locke, Rousseau et Kant. Pour cela, par le moyen de la recherche bibliographique nous partons de deux concepts fondamentaux de l'écrivain libertin et du psychanalyste autrichien : la loi de la nature de Sade et la pulsion de mort de Freud. Tous les deux concepts se réfèrent à une certain poussée à la destruction présent dans l'être humain, observées les différences parmi les auteurs. Le marquis de Sade réalise une espèce de reinterprétation de la théorie du contrat social de l'État moderne, en élevant ses fondements jusqu'à l'absurdité - ou en les dépassant - pour nous montrer que ces mêmes bases qui nous promettent la liberté, l'igualité et la sûreté peuvent nous conduire a un monde dystopique et despotique, en opérant un retour à l'état de nature, le point de départ où chaque être humain est pur objet à disposition de la jouissance de l'autre. En outre, dans la lecture de Kant avec Sade, nous comprendrons, auprès de Lacan, que l'éthique kantienne, l'apathie que l'être rationnel doit imposer à soi-même pour arriver au Bien Suprême, peut amener justement a son envers, le mal radical sadien. Nonobstant, à la fin, nous opérons une inversion : il y a deux temps dans la loi de la nature et la pulsion de mort, le principe de destruction peut aussi indiquer une volonté de création à partir du rien. Ainsi, basée sur l'éthique de la psychanalyse, l'éthique de la responsabilité par notre position de sujets, nous reprenons l'impératif catégorique kantien - maintenant vidé et dialectisé avec l'éthique sadienne - comme celui qui commande de « faire la loi », a fin de que la loi rencontre un limite, le point de capiton placé par la Loi symbolique
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