Proinsulin C-peptide induces c-Jun N-terminal kinase 1 expression in LEII mouse lung capillary endothelial cells

To characterize the roles of C-peptide in vascular homeostatic processes, we examined the genes regulated by C-peptide in LEII mouse lung microvascular endothelial cells. Treatment of the cells with C-peptide increased the expression of c-Jun N-terminal kinase 1 (JNK1) mRNA dose-dependently, accompanied by an increase in JNK1 protein content. Prior treatment of the cells with PD98059, an ERK kinase inhibitor or SB203580, a p38MAPK inhibitor, abrogated the C-peptide-elicited JNK1 mRNA expression. These results indicate that C-peptide increases JNK1 protein levels, possibly through ERK- and p38MAPK-dependent activation of JNK. gene transcription.

Primary immunodeficiency diseases in Latin America: Proceedings of the Second Latin American Society for Immunodeficiencies (LASID) Advisory Board

Early diagnosis and appropriate therapy are essential for the best prognosis and quality of life in patients with primary immunodeficiency diseases (PIDDs). Experts from several Latin American countries have been meeting on a regular basis as part of an ongoing effort to improve the diagnosis and treatment of PIDD in this region. Three programmes are in development that will expand education and training and improve access to testing facilities throughout Latin America. These programmes are: an educational outreach programme (The L-Project); an immunology fellowship programme; and the establishment of a laboratory network to expand access to testing facilities. This report provides the status of these programmes based on the most recent discussions and describes the next steps toward full implementation of these programmes. (C) 2010 SEICAP. Published by Elsevier Espana, S.L. All rights reserved.

Study of the mechanism of action of anoplin, a helical antimicrobial decapeptide with ion channel-like activity, and the role of the amidated C-terminus

Anoplin, an antimicrobial, helical decapeptide from wasp venom, looses its biological activities by mere deamidation of its C-terminus. Secondary structure determination, by circular dichroism spectroscopy in amphipathic environments, and lytic activity in zwitterionic and anionic vesicles showed quite similar results for the amidated and the carboxylated forms of the peptide. The deamidation of the C-terminus introduced a negative charge at an all-positive charged peptide, causing a loss of amphipathicity, as indicated by molecular dynamics simulations in TFE/water mixtures and this subtle modification in a peptide`s primary structure disturbed the interaction with bilayers and biological membranes. Although being poorly lytic, the amidated form, but not the carboxylated, presented ion channel-like activity on anionic bilayers with a well-defined conductance step; at approximately the same concentration it showed antimicrobial activity. The pores remain open at trans-negative potentials, preferentially conducting cations, and this situation is equivalent to the interaction of the peptide with bacterial membranes that also maintain a high negative potential inside. Copyright (C) 2007 European Peptide Society and John Wiley & Sons, Ltd.

On C(r)-closing for flows on orientable and non-orientable 2-manifolds

We provide an affirmative answer to the C(r)-Closing Lemma, r >= 2, for a large class of flows defined on every closed surface.

[(13)C(2)]- Acetaldehyde Promotes Unequivocal Formation of 1,N(2)-Propano-2 `-deoxyguanosine in Human Cells

Acetaldehyde is an environmentally widespread genotoxic aldehyde present in tobacco smoke, vehicle exhaust and several food products. Endogenously, acetaldehyde is produced by the metabolic oxidation of ethanol by hepatic NAD-dependent alcohol dehydrogenase and during threonine catabolism. The formation of DNA adducts has been regarded as a critical factor in the mechanisms of acetaldehyde mutagenicity and carcinogenesis. Acetaldehyde reacts with 2`-deoxyguanosine in DNA to form primarily N(2)-ethylidene-2`-deoxyguanosine. The subsequent reaction of N(2)-ethylidenedGuo with another molecule of acetaldehyde gives rise to 1,N(2)-propano-2`-deoxyguanosine (1,N(2)-propanodGuo), an adduct also found as a product of the crotonaldehyde reaction with dGuo. However, adducts resulting from the reaction of more than one molecule of acetaldehyde in vivo are still controversial. In this study, the unequivocal formation of 1,N(2)-propanodGuo by acetaldehyde was assessed in human cells via treatment with [(13)C(2)]-acetaldehyde. Detection of labeled 1,N(2)-propanodGuo was performed by HPLC/MS/MS. Upon acetaldehyde exposure (703 mu M), increased levels of both 1,N(2)-etheno-2`-deoxyguanosine (1,N(2)-epsilon dGuo), which is produced from alpha,beta-unsaturated aldehydes formed during the lipid peroxidation process, and 1,N(2)-propanodGuo were observed. The unequivocal formation of 1,N(2)-propanodGuo in cells exposed to this aldehyde can be used to elucidate the mechanisms associated with acetaldehyde exposure and cancer risk.

Prenylated benzoic acid derivatives from Piper aduncum L. and P. hostmannianum C. DC. (Piperaceae)

The bioactivity-guided fractionation of the crude extracts from leaves of Brazilian species Piper aduncum and Piper hostmannianum by means of bioautography using the fungi Cladosporium cladosporioides and C. sphaerospermum afforded prenylated methyl benzoate, chromenes, and dihydrobenzopyran derivatives as antifungal compounds. The isolation and structural elucidation of a new compound methyl 4-hydroxy-3-(2`-hydroperoxy-3`-methyl-3`-butenyl) benzoate were performed by application of chromatographic techniques and spectroscopic analyses. (C) 2009 Phytochemical Society of Europe. Published by Elsevier B.V. All rights reserved.

Entropy Drives an Attached Water Molecule from the C- to N-Terminus on Protonated Proline

Results from infrared photodissociation (IRPD) spectroscopy and kinetics of singly hydrated, protonated proline indicate that the water molecule hydrogen bonds preferentially to the formally neutral carboxylic acid at low temperatures and at higher temperatures to the protonated N-terminus, which bears the formal charge. Hydration isomer populations obtained from IRPD kinetic data as a function of temperature are used to generate a van`t Hoff plot that reveals that C-terminal binding is enthalpically favored by 4.2-6.4 kJ/mol, whereas N-terminal binding is entropically favored by 31-43 J/(mol K), consistent with a higher calculated barrier for water molecule rotation at the C-terminus.

Microwave-assisted solid-phase peptide synthesis at 60 degrees C: alternative conditions with low enantiomerization

Several conditions have been used in the coupling reaction of stepwise SPPS at elevated temperature (SPPS-ET), but we have elected the following as our first choice: 2.5-fold molar excess of 0.04-0.08 M Boc or Fmoc-amino acid derivative, equimolar amount of DIC/HOBt (1:1)or TBTU/DIPEA(1:3), 25% DMSO/toluene, 60 degrees C, conventional heating. In this study, aimed to further examine enantiomerization under such condition and study the applicability of our protocols to microwave-SPPS, peptides containing L-Ser, L-His, L-Cys and/or L-Met were manually synthesized traditionally, at 60 degrees C using conventional heating and at 60 degrees C using microwave heating. Detailed assessment of all crude peptides (in their intact and/or fully hydrolyzed forms) revealed that, except for the microwave-assisted coupling of L-Cys, all other reactions occurred with low levels of amino acid enantiomerization (<2%). Therefore, herein we (i) provide new evidences that our protocols for SPPS at 60 degrees C using conventional heating are suitable for routine use, (ii) demonstrate their appropriateness for microwave-assisted SPPS by Boc and Fmoc chemistries, (iii) disclose advantages and limitations of the three synthetic approaches employed. Thus, this study complements our past research on SPPS-ET and suggests alternative conditions for microwave-assisted SPPS. Copyright (C) 2009 European Peptide Society and John Wiley & Sons, Ltd.

Understanding Foreign Masters : the examples of Rabindranath Tagore and Fyodor Dostoyevskiy

The Indian author Rabindranath Tagore was received like royalty during his visits to the West after winning the Nobel Prize in 1913. Dreams of foreign cultures offered a retreat from a complicated age. In a time when the West appeared to be living under threat of disintegration and when industrialism seemed like a cul-de-sac, he appeared to offer the promise of a return to a lost paradise, a spiritual abode that is superior to the restless Western culture. However, Tagore’s popularity faded rapidly, most notably in England, the main target of his criticism. Soon after Tagore had won the Nobel Prize, the English became indignant at Tagore’s anti-colonial attitude.Tagore visited Sweden in 1921 and 1926 and was given a warm reception. His visits to Sweden can be seen as an episode in a longer chain of events. It brought to life old conceptions of India as the abode of spirituality on earth. Nevertheless, interest in him was a relatively short-lived phenomenon in Sweden. Only a few of his admirers in Sweden appreciated the complexity of Tagore’s achievements. His “anathema of mammonism”, as a Swedish newspaper called it, was not properly received. After a steady stream of translations his popularity flagged towards the end of the 1920s and then almost disappeared entirely. Tagores visits in Sweden gave an indication that India was on the way to liberate itself from its colonial legacy, which consequently contributed to the waning of his popularity in the West. In the long run, his criticism of the drawbacks in the western world became too obvious to maintain permanent interest. The Russian author Fyodor Dostoyevskiy’s Crime and Punishment (1866) has enticed numerous interpretations such as the purely biographical approach. In the nervous main character of the novel, the young student Raskolnikov, one easily recognizes Dostoyevskiy himself. The novel can also be seen as a masterpiece of realistic fiction. It gives a broad picture of Saint Petersburg, a metropolis in decay. Crime and Punishment can also be seen as one of the first examples of a modern psychological novel, since it is focused on the inner drama of its main character, the young student Raskolnikov. His actions seem to be governed by mere coincidences, dreams and the spur of the moment. it seems fruitful to study the novel from a psychoanalytical approach. In his book Raskolnikov: the way of the divided towards unity in Crime and Punishment (1982), a Swedish scholar, Owe Wikström, has followed this line of interpretation all the way to Freud’s disciple C G Jung. In addition to this, the novel functions as an exciting crime story. To a large extent it is Viktor Sjklovskij and other Russian formalists from the 1920s and onwards who have taught the western audience to understand the specific nature of the crime story. The novel could be seen as a story about religious conversion. Like Lasarus in the Bible (whose story attracts a lot of attention in the novel) Raskolnikov is awakened from the dead, and together with Sonja he starts a completely new life. The theme of conversion has a special meaning for Dostoyevskiy. For him the conversion meant an acknowledgement of the specific nature of Russia itself. Crime and punishment mirrors the conflict between traditional Russian values and western influences that has been obvious in Russia throughout the history of the country. The novel reflects a dialogue that still continues in Russian society. The Russian literary historian Mikhail Bakhtin, who is probably the most famous interpreter of the works of Dostoyevskiy, has become famous precisely by emphasizing the importance of dialogues in novels like Crime and Punishment. According to Bakhtin, this novel is characterized by its multitude of voices. Various ideas are confronted with each other, and each one of them is personified by one of the characters in the novel. The author has resigned from his position as the superior monitor of the text, and he leaves it to the reader to decide what interpretation is the correct one..The aim of the present study is thus to analyze the complex reactions in the west to Tagore’s visits in Sweden and to Fyodor Dostoyevskiys novel Crime and Punishment.. This leads to more general conclusions on communication between cultures.

State–society cycles and political pacts in a national–dependent society: Brazil

The history of independent Brazil may be divided into three major state–society cycles, and, after 1930, five political pacts or class coalitions can be identified. These pacts were nationalist; only in the 1990s did the Brazilian elites surrender to the neoliberal hegemony. Yet, since the mid-2000s they have been rediscovering the idea of the nation. The main claim of the essay is that Brazilian elites and Brazilian society are “national–dependent”, that is, they are ambivalent and contradictory, requiring an oxymoron to define them. They are dependent because they often see themselves as “European” and the mass of the people as inferior. But Brazil is big enough, and there are enough common interests around its domestic market, to make the Brazilian nation less ambivalent. Today Brazil is seeking a synthesis between the last two political cycles – between social justice and economic development in the framework of democracy.

Upregulation of soluble and membrane-bound human leukocyte antigen G expression is primarily observed in the milder histopathological stages of chronic hepatitis C virus infection

Chronic hepatitis C virus (HCV) infection is a worldwide health problem that may evolve to cirrhosis and hepatocellular carcinoma. Incompletely understood immune system mechanisms have been associated with impaired viral clearance. The nonclassical class I human leukocyte antigen G (HLA-G) molecule may downregulate immune system cell functions exhibiting well-recognized tolerogenic properties. HCV genotype was analyzed in chronic HCV-infected patients. Because HLA-G expression may be induced by certain viruses, we evaluated the presence of HLA-G in the liver microenvironment obtained from 89 biopsies of patients harboring chronic HCV infection and stratified according to clinical and histopathological features. Overall, data indicated that HCV genotype 1 was predominant, especially subgenotype 1a, with a prevalence of 87%. HLA-G expression was observed in 45(51%) liver specimens, and it was more frequent in milder stages of chronic hepatitis (67.4%) than in moderate (27.8%; p = 0.009) and severe (36.0%; p = 0.021) stages of the disease. Altogether, these results suggest that the expression of HLA-G in the context of HCV is a complex process modulated by many factors, which may contribute to an immunologic environment favoring viral persistence. However, because the milder forms predominantly expressed HLA-G, a protective role of this molecule may not be excluded. (C) 2012 American Society for Histocompatibility and Immunogenetics. Published by Elsevier B.V. All rights reserved.

KIR genes and their human leukocyte antigen ligands in the progression to cirrhosis in patients with chronic hepatitis C

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Transient and d.c. analysis of the operation mechanism of light-emitting electrochemical cells

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)