@article {8519, title = {Epigenetic Signals on Plant Adaptation: A Biotic Stress Perspective.}, journal = {Curr Protein Pept Sci}, year = {2016}, month = {2016 Jul 24}, abstract = {

For sessile organisms such as plants, regulatory mechanisms of gene expression are vital, since they remain exposed to climatic and biological threats. Thus, they have to face hazards with instantaneous reorganization of their internal environment. For this purpose, besides the use of transcription factors, the participation of chromatin as an active factor in the regulation of transcription is crucial. Chemical changes in chromatin structure affect the accessibility of the transcriptional machinery and acting in signaling, engaging/inhibiting factors that participate in the transcription processes. Mechanisms in which gene expression undergoes changes without the occurrence of DNA gene mutations in the monomers that make up DNA, are understood as epigenetic phenomena. These include (1) post-translational modifications of histones, which results in stimulation or repression of gene activity and (2) cytosine methylation in the promoter region of individual genes, both preventing access of transcriptional activators as well as signaling the recruitment of repressors. There is evidence that such modifications can pass on to subsequent generations of daughter cells and even generations of individuals. However, reports indicate that they persist only in the presence of a stressor factor (or an inductor of the above-mentioned modifications). In its absence, these modifications weaken or lose heritability, being eliminated in the next few generations. In this review, it is argued how epigenetic signals influence gene regulation, the mechanisms involved and their participation in processes of resistance to biotic stresses, controlling processes of the plant immune system.

}, issn = {1875-5550}, author = {Neto, Jos{\'e} Ribamar Costa Ferreira and da Silva, Manass{\'e}s Daniel and Pandolfi, Valesca and Crovella, Sergio and Benko-Iseppon, Ana Maria and Kido, {\'E}derson Akio} } @article {3491, title = {Exome analysis of HIV patients submitted to dendritic cells therapeutic vaccine reveals an association of CNOT1 gene with response to the treatment.}, journal = {J Int AIDS Soc}, volume = {17}, year = {2014}, month = {2014}, pages = {18938}, abstract = {

INTRODUCTION: With the aim of searching genetic factors associated with the response to an immune treatment based on autologous monocyte-derived dendritic cells pulsed with autologous inactivated HIV, we performed exome analysis by screening more than 240,000 putative functional exonic variants in 18 HIV-positive Brazilian patients that underwent the immune treatment.

METHODS: Exome analysis has been performed using the ILLUMINA Infinium HumanExome BeadChip. zCall algorithm allowed us to recall rare variants. Quality control and SNP-centred analysis were done with GenABEL R package. An in-house implementation of the Wang method permitted gene-centred analysis.

RESULTS: CCR4-NOT transcription complex, subunit 1 (CNOT1) gene (16q21), showed the strongest association with the modification of the response to the therapeutic vaccine (p=0.00075). CNOT1 SNP rs7188697 A/G was significantly associated with DC treatment response. The presence of a G allele indicated poor response to the therapeutic vaccine (p=0.0031; OR=33.00; CI=1.74-624.66), and the SNP behaved in a dominant model (A/A vs. A/G+G/G p=0.0009; OR=107.66; 95\% CI=3.85-3013.31), being the A/G genotype present only in weak/transient responders, conferring susceptibility to poor response to the immune treatment.

DISCUSSION: CNOT1 is known to be involved in the control of mRNA deadenylation and mRNA decay. Moreover, CNOT1 has been recently described as being involved in the regulation of inflammatory processes mediated by tristetraprolin (TTP). The TTP-CCR4-NOT complex (CNOT1 in the CCR4-NOT complex is the binding site for TTP) has been reported as interfering with HIV replication, through post-transcriptional control. Therefore, we can hypothesize that genetic variation occurring in the CNOT1 gene could impair the TTP-CCR4-NOT complex, thus interfering with HIV replication and/or host immune response.

CONCLUSIONS: Being aware that our findings are exclusive to the 18 patients studied with a need for replication, and that the genetic variant of CNOT1 gene, localized at intron 3, has no known functional effect, we propose a novel potential candidate locus for the modulation of the response to the immune treatment, and open a discussion on the necessity to consider the host genome as another potential variant to be evaluated when designing an immune therapy study.

}, keywords = {AIDS Vaccines, Dendritic Cells, Exome, HIV Infections, Humans, Immunity, Humoral, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Transcription Factors, Treatment Outcome}, issn = {1758-2652}, doi = {10.7448/IAS.17.1.18938}, author = {Moura, Ronald and Pontillo, Alessandra and d{\textquoteright}Adamo, Pio and Pirastu, Nicola and Campos Coelho, Antonio and Crovella, Sergio} } @article {1955, title = {The effect of clodronate on a mevalonate kinase deficiency cellular model.}, journal = {Inflamm Res}, volume = {61}, year = {2012}, month = {2012 Dec}, pages = {1363-7}, abstract = {

BACKGROUND: A potential anti-inflammatory effect of clodronate--an aminobisphosphonate--was described to antagonize the pro-inflammatory effects of the block in the mevalonate pathway, the main feature of a rare auto-inflammatory disease called mevalonate kinase deficiency (MKD).

OBJECTIVE: In this study we evaluated the potential anti-inflammatory effect of clodronate in MKD--a still orphan drug pediatric disease.

METHODS: We studied some biological parameters, nitric oxide production using Griess reagents and programmed cell death by flow cytometry, as common inflammatory parameters in MKD, in the presence of different doses of clodronate (1, 10 and 100 μM).

RESULTS: In our cellular model and in monocytes from patients with MKD, clodronate induced an increase in programed cell death and nitric oxide production in comparison with non-treated cells.

CONCLUSION: Our findings suggest that clodronate does not have an anti-inflammatory effect as previously reported but that it increases the epiphenomena of this pediatric disease.

}, keywords = {Adolescent, Adult, Alendronate, Animals, Anti-Inflammatory Agents, Apoptosis, Cell Line, Cells, Cultured, Child, Clodronic Acid, Female, Humans, Inflammation, Lipopolysaccharides, Male, Mevalonate Kinase Deficiency, Mice, Models, Biological, Monocytes, Nitric Oxide, Young Adult}, issn = {1420-908X}, doi = {10.1007/s00011-012-0537-4}, author = {Zanin, Valentina and Marcuzzi, Annalisa and Piscianz, Elisa and Vuch, Josef and Bianco, Anna Monica and Monasta, Lorenzo and Decorti, Giuliana and Crovella, Sergio} } @article {1623, title = {Ethnobotanical bioprospection of candidates for potential antimicrobial drugs from Brazilian plants: state of art and perspectives.}, journal = {Curr Protein Pept Sci}, volume = {11}, year = {2010}, month = {2010 May}, pages = {189-94}, abstract = {

Despite of the high biological diversity and traditional use of medicinal plants in Brazil, no comprehensive ethnobotanic review of plants with potential antimicrobial effects is available. In the present work own field information is aggregated with a literature review, identifying 433 Brazilian plant species potentially useful for identification of antimicrobial peptides. They included mainly woody species, distributed on 100 plant families (93 angiosperms and 7 pteridophytes) and 266 genera, covering all Brazilian regions and ecosystems. Main plant parts and indications for their use are presented and discussed, revealing the high potential that these plants present for the future planning strategies regarding the future development of antimicrobial drugs.

}, keywords = {Anti-Infective Agents, Biodiversity, Brazil, Ethnobotany, Plants}, issn = {1875-5550}, author = {Benko-Iseppon, Ana Maria and Crovella, Sergio} }