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1.
J Neural Transm (Vienna) ; 126(11): 1517, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31222607

RESUMO

The original version of this article unfortunately contained a mistake. The author would like to include the below acknowledgement section.

2.
Genet Mol Biol ; 40(4): 751-758, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29111564

RESUMO

Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

3.
J Neural Transm (Vienna) ; 123(12): 1479-1490, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27503083

RESUMO

rTMS is increasingly used for a variety of neuropsychiatric conditions. There are data to support 'fast' rTMS (≥10 Hz) having some positive effects on cognitive functioning, but a dearth of research looking at any such effects of 'slow' rTMS. This question is important as cognitive dysfunction accompanies many neuropsychiatric conditions and neuromodulation that potentially enhances or hinders such functioning has important clinical consequences. To determine cognitive effects of slow (≤1 Hz) rTMS, a systematic review of randomized control trials assayed cognition in neurological, psychiatric, and healthy volunteer ≤1 Hz rTMS paradigms. Both active (fast rTMS) and placebo comparators were included. 497 Records were initially obtained; 20 met inclusion criteria for evaluation. Four major categories emerged: mood disorders; psychotic disorders; cerebrovascular accidents; and 'other' (PTSD, OCD, epilepsy, anxiety, and tinnitus). Cognitive effects were measured across several domains: attention, executive functioning, learning, and psychomotor speed. Variability of study paradigms and reporting precluded meta-analytical analysis. No statistically significant improvement or deterioration was consistently found in any cognitive domain or illness category. These data support the overall safety of rTMS in not adversely affecting cognitive functioning. There are some data indicating that rTMS might have cognitive enhancing potential, but these are too limited at this time to make any firm conclusions, and the literature is marked by considerable heterogeneity in study parameters that hinder interpretation. Greater consensus is required in future studies in cognitive markers, and particularly in reporting of protocols. Future work should evaluate the effects of rTMS on cognitive training.


Assuntos
Transtornos Cognitivos/terapia , Estimulação Magnética Transcraniana/métodos , Atenção , Transtornos Cognitivos/etiologia , Função Executiva , Humanos , Transtornos Mentais/complicações , Transtornos do Humor/complicações , Testes Neuropsicológicos , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/complicações
4.
Extremophiles ; 19(5): 989-99, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26216108

RESUMO

The extremophile Deinococcus radiodurans wild type R1 produces peptidases (metallo- and serine-) in TGY medium and in the media supplemented with human hair (HMY) and chicken feathers (FMY). Enzymatic screening on agar plates revealed peptidase activity. In TGY medium metallopeptidases were detected corresponding to a molecular mass range of 300-85 kDa (gelatinases); 280-130 (caseinases) and a 300 and a 170 kDa (keratinases); and a gelatinolytic serine peptidase (75 kDa). In HMY medium after 144 h, D. radiodurans produced keratinase (290 U/ml), gelatinase (619 U/ml) and sulfite (26 µg/ml). TGY medium produced higher proteolytic activity: 950 U/ml of gelatinolytic (24 h); 470 U/ml of keratinolytic (24 h) and 110 U/ml of caseinolytic (72 h). In the FMY medium, we found gelatinolytic (317 U/ml), keratinolytic (43 U/ml) and caseinolytic (85 U/ml) activities. The sulfite had a maximum release at 48 h (8.1 µg/ml). Enzymography analysis revealed that the keratinases degraded keratin after 24 h of reaction. The addition of sodium sulfite (1.0 %) improved the keratin degradation. Environmental Scanning Electron microscopy revealed alterations such as damage and holes in the hair fiber cuticle after D. radiodurans growth. This work presents for the first time D. radiodurans as a new keratinolytic microorganism.


Assuntos
Proteínas de Bactérias/química , Deinococcus/enzimologia , Metaloendopeptidases/química , Proteínas de Bactérias/metabolismo , Caseínas/química , Gelatina/química , Queratinas/química , Metaloendopeptidases/metabolismo
5.
An Acad Bras Cienc ; 86(3): 1385-94, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25098311

RESUMO

Extracts of Echinodorus grandiflorus obtained from dried leaves by three different techniques were evaluated by bacterial lysogenic induction assay (Inductest) in relation to their genotoxic properties. Before being added to test cultures, extracts were sterilized either by steam sterilization or ultraviolet light. Only the extracts prepared by infusion and steam sterilized have shown genotoxic activity. The phytochemical analysis revealed the presence of the flavonoids isovitexin, isoorientin, swertisin and swertiajaponin, isolated from a genotoxic fraction. They were assayed separately and tested negative in the Inductest protocol. The development of browning color and sweet smell in extracts submitted to heat, prompted further chemical analysis in search for Maillard's reaction precursors. Several aminoacids and reducing sugars were cast in the extract. The presence of characteristic Maillard's melanoidins products was determined by spectrophotometry in the visible region and the inhibition of this reaction was observed when its characteristic inhibitor, sodium bisulfite, was added prior to heating. Remarkably, this is the first paper reporting on the appearance of such compounds in a phytomedicine preparation under a current phytopharmaceutical procedure. The genotoxic activity of such heat-prepared infusions imply in some risk of developing degenerative diseases for patients in long-term, uncontrolled use of such phytomedicines.


Assuntos
Alismataceae/toxicidade , Dano ao DNA/efeitos dos fármacos , DNA Bacteriano/efeitos dos fármacos , Extratos Vegetais/toxicidade , Alismataceae/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Testes de Mutagenicidade/métodos
6.
Neurosci Biobehav Rev ; 157: 105511, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38104788

RESUMO

Cognitive flexibility is a fundamental process that underlies adaptive behaviour in response to environmental change. Studies examining the profile of cognitive flexibility in autism spectrum disorder (ASD) have reported inconsistent findings. To address whether difficulties with cognitive flexibility are characteristic of autism, we conducted a random-effects meta-analysis and employed subgroup analyses and meta-regression to assess the impact of relevant moderator variables such as task, outcomes, and age. Fifty-nine studies were included and comprised of 2122 autistic individuals without intellectual disabilities and 2036 neurotypical controls, with an age range of 4 to 85 years. The results showed that autistic individuals have greater difficulties with cognitive flexibility, with an overall statistically significant small to moderate effect size. Subgroup analyses revealed a significant difference between task outcomes, with perseverative errors obtaining the largest effect size. In summary, the present meta-analysis highlights the existence of cognitive flexibility difficulties in autistic people, in the absence of learning disabilities, but also that this profile is characterised by substantial heterogeneity. Potential contributing factors are discussed.


Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Humanos , Pré-Escolar , Criança , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/psicologia , Cognição , Função Executiva/fisiologia
7.
Microb Ecol ; 65(2): 325-35, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23001596

RESUMO

Martian surface microbial inhabitants would be challenged by a constant and unimpeded flux of UV radiation, and the study of analog model terrestrial environments may be of help to understand how such life forms could survive under this stressful condition. One of these environments is the Atacama Desert (Chile), a well-known Mars analog due to its extreme dryness and intense solar UV radiation. Here, we report the microbial diversity at five locations across this desert and the isolation of UVC-tolerant microbial strains found in these sites. Denaturing gradient gel electrophoresis (DGGE) of 16S rDNA sequences obtained from these sites showed banding patterns that suggest distinct and complex microbial communities. Analysis of 16S rDNA sequences obtained from UV-tolerant strains isolated from these sites revealed species related to the Bacillus and Pseudomonas genera. Vegetative cells of one of these isolates, Bacillus S3.300-2, showed the highest UV tolerance profile (LD(10) = 318 J m(2)), tenfold higher than a wild-type strain of Escherichia coli. Thus, our results show that the Atacama Desert harbors a noteworthy microbial community that may be considered for future astrobiological-related research in terms of UV tolerance.


Assuntos
Bactérias/isolamento & purificação , Bactérias/efeitos da radiação , Clima Desértico , Microbiologia do Solo , Bactérias/classificação , Bactérias/genética , Biodiversidade , Chile , DNA Bacteriano/genética , Eletroforese em Gel de Gradiente Desnaturante , Exobiologia , RNA Ribossômico 16S/genética , Tolerância a Radiação , Raios Ultravioleta
8.
Curr Oncol ; 30(4): 4094-4109, 2023 04 07.
Artigo em Inglês | MEDLINE | ID: mdl-37185424

RESUMO

HER2-enriched tumors are responsible for 20% of breast tumors and have high rates of immune infiltrates in the tumor stroma that respond favorably to neoadjuvant chemotherapy. In the context of tumors, telomeres control cell death and prevent tumor cells from replicating discontinuously, leading to their immortalization. This study aimed to evaluate the presence of tumor-infiltrating lymphocytes, hTERT expression, hTERT promoter mutation, and leukocyte telomere length in HER2-enriched breast tumors. A total of 103 cases were evaluated, 19 with pathologic complete response. The TILs percentage was above ≥10 in 44 cases (43%) and significantly present in patients ≥50 years of age. hTERT staining positivity was mostly nuclear, significantly present in the non-pCR group, and associated with a lower survival rate. Leukocyte telomeres were elongated for HER2-enriched tumors, and in multivariate analysis, shortening was associated with an increased risk of death. Overall, our results show that the nuclear and cytoplasmic presence of hTERT may indicate a worse prognosis and that leukocyte telomere elongation is a protective factor.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linfócitos do Interstício Tumoral/metabolismo , Linfócitos do Interstício Tumoral/patologia , Terapia Neoadjuvante/métodos , Prognóstico , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo
9.
Life (Basel) ; 13(11)2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-38004348

RESUMO

The purine nucleobases adenine and guanine are complex organic molecules that are essential for life. Despite their ubiquitous presence on Earth, purines have yet to be detected in observations of astronomical environments. This work therefore proposes to study the infrared spectra of purines linked to terrestrial biochemical processes under conditions analogous to those found in the interstellar medium. The infrared spectra of adenine and guanine, both in neat form and embedded within an ice made of H2O:NH3:CH4:CO:CH3OH (10:1:1:1:1), were analysed with the aim of determining which bands attributable to adenine and/or guanine can be observed in the infrared spectrum of an astrophysical ice analogue rich in other volatile species known to be abundant in dense molecular clouds. The spectrum of adenine and guanine mixed together was also analysed. This study has identified three purine nucleobase infrared absorption bands that do not overlap with bands attributable to the volatiles that are ubiquitous in the dense interstellar medium. Therefore, these three bands, which are located at 1255, 940, and 878 cm-1, are proposed as an infrared spectral signature for adenine, guanine, or a mixture of these molecules in astrophysical ices. All three bands have integrated molar absorptivity values (ψ) greater than 4 km mol-1, meaning that they should be readily observable in astronomical targets. Therefore, if these three bands were to be observed together in the same target, then it is possible to propose the presence of a purine molecule (i.e., adenine or guanine) there.

10.
Anticancer Res ; 39(4): 1859-1867, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30952726

RESUMO

BACKGROUND: Proteins overexpressed in malignant tissues form important targets in the development of targeted therapeutics, and aptamers comprise an important affinity agent for therapy and drug delivery. In this study, aberrantly expressed mucin 1 glycoprotein was investigated as a therapeutic target in a breast cancer model. MATERIALS AND METHODS: In order to determine the feasibility of using an aptamer against mucin 1 (aptA) as carrier of the cytotoxic compound 1,10-phenanthroline to MCF-7 cells, as a potential radiosensitizer, was studied in experiments using circular dichroism and rhodamine labelling by fluorescent microscopy and flow cytometry. RESULTS: 1,10-Phenanthroline can be intercalated within aptA when complexed with Fe(II) ions, with dissociation constant (Kd) of 30 µM. The complex was subsequently capable of binding to and being internalised in MCF-7 breast cancer cells. CONCLUSION: aptA can carry 1,10-phenanthroline to cancer cells specifically and this complex represents a potential target-directed anticancer therapy.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Neoplasias da Mama/metabolismo , Portadores de Fármacos , Endocitose , Mucina-1/metabolismo , Fenantrolinas/metabolismo , Radiossensibilizantes/metabolismo , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/radioterapia , Estudos de Viabilidade , Feminino , Compostos Ferrosos/química , Humanos , Células MCF-7 , Mucina-1/genética , Fenantrolinas/química , Fenantrolinas/farmacologia , Radiossensibilizantes/farmacologia
11.
Photochem Photobiol ; 95(2): 618-626, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30103257

RESUMO

Rational use of water is a major challenge for governments and global organizations, with easy and inexpensive interventions being sought by communities that are not supplied with drinking water. In this context, solar disinfection (SODIS) has shown great efficiency for water disinfection. To speed up the process and improve inactivation, we studied the effects of methylene blue (MB) as a photodynamic agent because of its ability to absorb visible light (red wavelength) and generate singlet oxygen as a reactive species, thereby inactivating bacteria and viruses present in water. In this study, samples of clean mineral water were artificially contaminated with Gram-positive (Staphylococcus epidermidis or Deinococcus radiodurans) or with Gram-negative strains (Escherichia coli or Salmonella typhimurium) and exposed to traditional SODIS or to MB-SODIS. A lethal synergistic effect was observed when cultures were illuminated in the presence of MB. The obtained results indicate that bacterial inactivation can be achieved in a much shorter time when using MB associated with SODIS treatment. Therefore, this technique was able to provide safe water for consumption through the inactivation of microorganisms in general, including pathogens and some strains resistant to the traditional SODIS procedure, thus allowing its use in areas usually less exposed to sunlight.

12.
Sci Rep ; 9(1): 9554, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266976

RESUMO

The Microbacterium sp. LEMMJ01 isolated from Antarctic soil does not belong to any of the nearest species identified in the RDP database. Under UV radiation (A, B and C wavebands) the survival fractions of Microbacterium sp. cells were much higher compared with wild-type E. coli K12A15. Especially remarkable for an Antarctic bacterium, an expressive resistance against high UV-B doses was observed. The increased survival of DNA repair-proficient E. coli grown overnight added of 0.1 mg/ml or 1 mg/ml of the whole pigment extract produced by Microbacterium sp. revealed that part of the resistance of Microbacterium sp. against UV-B radiation seems to be connected with photoprotection by its pigments. Scanning electron microscopy revealed that UV-A and UV-B ensued membrane alterations only in E. coli. The APCI-MS fingerprints revealed the diagnostic ions for neurosporene (m/z 580, 566, 522, 538, and 524) synergism for the first time in this bacterium by HPLC-MS/MS analysis. Carotenoids also were devoid of phototoxicity and cytotoxicity effects in mouse cells and in human keratinocytes and fibroblasts.


Assuntos
Actinobacteria/química , Actinobacteria/efeitos da radiação , Carotenoides/química , Tolerância a Radiação , Raios Ultravioleta , Actinobacteria/classificação , Actinobacteria/genética , Regiões Antárticas , Carotenoides/farmacologia , Cromatografia Líquida de Alta Pressão , Relação Dose-Resposta à Radiação , Escherichia coli/genética , Escherichia coli/efeitos da radiação , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/metabolismo , Viabilidade Microbiana , Filogenia , RNA Ribossômico 16S/genética , Espectrometria de Massas em Tandem
13.
Oncol Rep ; 34(4): 1667-74, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26238022

RESUMO

Molecular evidence indicates that alterations in genes involved in the maintenance of genome stability may be related to susceptibility to bladder carcinoma. Our goal was to evaluate the prognostic role of base excision repair (BER) genes in a cohort of patients diagnosed with primary urothelial carcinoma of the bladder (UCB). The levels of all APE1, XRCC1 and POLB transcripts were detected by quantitative real-time PCR (qPCR) technique in tumor samples from 52 patients undergoing transurethral resection (TUR) for primary UCB at the Department of Urology, Brazilian National Cancer Institute, Rio de Janeiro. Increased levels of APE1, XRCC1 and POLB transcripts were significantly associated with high-grade tumors when compared to these levels in low-grade tumors (p<0.01) and could be attributed to different mechanisms of transcriptional regulation as a response to tumorigenesis and oxidative stress. By analyzing the collected data in the present study, regardless of pathological grade or stage, univariate analysis revealed that the reduced levels of APE1 transcripts were significantly associated with cancer-specific mortality (p=0.032). Furthermore, the variant genotype (TG/GG) of the APE1 T1349G polymorphism was observed in 75% of a subset of patients who concomitantly experienced reduced levels of the APE1 transcript and death and/or recurrence events. Taken together, our data reinforce the idea that human DNA repair mechanisms must be finely regulated in order to avoid instability leading to tumorigenesis and poor clinical outcomes in UCB patients.


Assuntos
DNA Polimerase beta/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/genética , Proteínas de Ligação a DNA/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Bexiga Urinária/genética , Idoso , Idoso de 80 Anos ou mais , Brasil , DNA Polimerase beta/biossíntese , Reparo do DNA/genética , DNA Liase (Sítios Apurínicos ou Apirimidínicos)/biossíntese , Proteínas de Ligação a DNA/biossíntese , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Polimorfismo de Nucleotídeo Único , Prognóstico , Análise de Sobrevida , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia , Proteína 1 Complementadora Cruzada de Reparo de Raio-X
14.
BMC Evol Biol ; 4: 29, 2004 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-15333143

RESUMO

BACKGROUND: DNA repair genes encode proteins that protect organisms against genetic damage generated by environmental agents and by-products of cell metabolism. The importance of these genes in life maintenance is supported by their high conservation, and the presence of duplications of such genes may be easily traced, especially in prokaryotic genomes. RESULTS: The genome sequences of two Xanthomonas species were used as the basis for phylogenetic analyses of genes related to DNA repair that were found duplicated. Although 16S rRNA phylogenetic analyses confirm their classification at the basis of the gamma proteobacteria subdivision, differences were found in the origin of the various genes investigated. Except for lexA, detected as a recent duplication, most of the genes in more than one copy are represented by two highly divergent orthologs. Basically, one of such duplications is frequently positioned close to other gamma proteobacteria, but the second is often positioned close to unrelated bacteria. These orthologs may have occurred from old duplication events, followed by extensive gene loss, or were originated from lateral gene transfer (LGT), as is the case of the uvrD homolog. CONCLUSIONS: Duplications of DNA repair related genes may result in redundancy and also improve the organisms' responses to environmental challenges. Most of such duplications, in Xanthomonas, seem to have arisen from old events and possibly enlarge both functional and evolutionary genome potentiality.


Assuntos
Reparo do DNA/genética , Evolução Molecular , Duplicação Gênica , Genes Bacterianos/genética , Xanthomonas/genética , Enzimas Reparadoras do DNA/genética , DNA Bacteriano/genética , Genoma Bacteriano , Filogenia , Xanthomonas/enzimologia
15.
Mutat Res ; 544(2-3): 143-57, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14644316

RESUMO

Chemotherapeutic agents such as mitomycin C or nitrogen mustards induce DNA inter-strand cross-links (ICL) and are highly toxic, thus constituting an useful tool to treat some human degenerative diseases, such as cancer. Additionally, psoralens plus UV-A (PUVA), which also induce ICL, find use in treatment of patients afflicted with psoriasis and vitiligo. The repair of DNA ICL generated by different molecules involves a number of multi-step DNA repair pathways. In bacteria, as in eukaryotic cells, if DNA ICL are not tolerated or repaired via nucleotide excision repair (NER), homologous recombination or translesion synthesis pathways, these DNA lesions may lead to mutations and cell death. Herein, we bring new insights to the role of Escherichia coli nucleotide excision repair genes uvrA, uvrB and uvrC in the repair of DNA damage induced by some chemotherapeutic agents and psoralen derivatives plus UV-A. These new observations point to a novel role for the UvrB protein, independent of its previously described role in the Uvr(A)BC complex, which could be specific for repair of monoadducts, intra-strand biadducts and/or ICL.


Assuntos
Antineoplásicos/farmacologia , Adutos de DNA/efeitos dos fármacos , Reparo do DNA/genética , Escherichia coli/genética , Furocumarinas/farmacologia , Raios Ultravioleta , Reparo do DNA/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Humanos
16.
J Clin Neurophysiol ; 31(6): 541-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25462140

RESUMO

PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has attracted attention as a putative clinical neuromodulatory tool, including for ameliorating hallucinations, although existing clinical data are inconsistent. There is a notable paucity of research on its physiological effects on normal neuronal functioning. METHODS: We neuroimaged 24 healthy adult volunteers undertaking a variable loading passive auditory task, randomized into 2 matched and double-masked groups: half received a 17-minute 1 Hz right temporoparietal rTMS paradigm and half sham rTMS. RESULTS: One hertz rTMS led to attenuation of the underlying auditory cortex response to the stimulus and a contralateral increase in cortical activity. Subanalysis of the auditory tasks demonstrated that rTMS effects varied with stimulus frequency and differences between the active and sham conditions were lost at the highest frequency. CONCLUSIONS: This work is, to the best of our knowledge, the first to neuroimage the effects of a "hallucinatory rTMS protocol" on basic auditory processing in healthy controls. Our data demonstrated that a so-called "inhibitory paradigm" can also produce distal neuronal activation and that effects can vary with neural loading. These results highlight the insufficient knowledge of the effects of rTMS on normal physiology, and this, combined with a lack of consensus on clinical trial parameters, may be contributing to the ambivalent data in therapeutic trials.


Assuntos
Córtex Auditivo/fisiologia , Mapeamento Encefálico/métodos , Alucinações/terapia , Estimulação Magnética Transcraniana/métodos , Estimulação Acústica , Adulto , Alucinações/diagnóstico , Alucinações/fisiopatologia , Voluntários Saudáveis , Humanos , Londres , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
17.
DNA Repair (Amst) ; 12(1): 63-72, 2013 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-23245695

RESUMO

Cisplatin is currently used in tumor chemotherapy to induce the death of malignant cells through blockage of DNA replication. It is a commonly used chemotherapeutic agent binding mono- or bifunctionally to guanines in DNA. Escherichia coli K12 mutant strains deficient in nucleotide excision repair (NER) were submitted to increasing concentrations of cisplatin, and the results revealed that uvrA and uvrB mutants are sensitive to this agent, while uvrC and cho mutants remain as the wild type strain. The time required for both gene expression turn-off and return to normal weight DNA in wild-type E. coli was not accomplished even after 4 h post-treatment with cisplatin, while the same process takes place within 1.5 h after ultraviolet radiation (UV). Besides, a heavily damaging action of cisplatin can be seen not only by persistent nicks on genomic DNA, but also by NER gene expression exceeding manifold that seen after equivalent lethal doses of UV. Moreover, cisplatin caused an increase in uvrB gene expression from its putative upstream promoter P3 in an SOS-independent manner.


Assuntos
Antineoplásicos/toxicidade , Cisplatino/toxicidade , Quebras de DNA de Cadeia Simples , Escherichia coli/genética , Resposta SOS em Genética/genética , Adenosina Trifosfatases/genética , Adenosina Trifosfatases/metabolismo , DNA Helicases/genética , DNA Helicases/metabolismo , DNA Bacteriano/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endodesoxirribonucleases/genética , Endodesoxirribonucleases/metabolismo , Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Mutação , Regiões Promotoras Genéticas , Transcrição Gênica , Raios Ultravioleta , Regulação para Cima
18.
Med Hypotheses ; 78(4): 435-41, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22285198

RESUMO

Cancer cells display high proliferation rates and survival provided by high glycolysis, chemoresistance and radioresistance, metabolic features that appear to be activated with malignancy, and seemed to have arisen as early in evolution as in unicellular/prokaryotic organisms. Based on these assumptions, we hypothesize that aggressive phenotypes found in malignant cells may be related to acquired unicellular behavior, launched within a tumor when viral and prokaryotic homologs are overexpressed performing likely robust functions. The ensemble of these expressed viral and prokaryotic close homologs in the proteome of a tumor tissue gives them advantage over normal cells. To assess the hypothesis validity, sequences of human proteins involved in apoptosis, energetic metabolism, cell mobility and adhesion, chemo- and radio-resistance were aligned to homologs present in other life forms, excluding all eukaryotes, using PSI-BLAST, with further corroboration from data available in the literature. The analysis revealed that selected sequences of proteins involved in apoptosis and tumor suppression (as p53 and pRB) scored non-significant (E-value>0.001) with prokaryotic homologs; on the other hand, human proteins involved in cellular chemo- and radio-resistance scored highly significant with prokaryotic and viral homologs (as catalase, E-value=zero). We inferred that such upregulated and/or functionally activated proteins in aggressive malignant cells represent a toolbox of modern human homologs evolved from a similar key set that have granted survival of ancient prokaryotes against extremely harsh environments. According to what has been discussed along this analysis, high mutation rates usually hit hotspots in important conserved protein domains, allowing uncontrolled expansion of more resistant, death-evading malignant clones. That is the case of point mutations in key viral proteins affording viruses escape to chemotherapy, and human homologs of such retroviral proteins (as Ras, Akt and EGFR) can elicit the same phenotype. Furthermore, a corollary to this hypothesis presumes that target-directed anti-cancer therapy should target human protein domains of low similarity to prokaryotic homologs for a well-succeeded anti-cancer therapy.


Assuntos
Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Genes Bacterianos/genética , Genes Neoplásicos/genética , Fenótipo , Células Procarióticas/química , Apoptose/genética , Adesão Celular/genética , Movimento Celular/genética , Biologia Computacional , Metabolismo Energético/genética , Humanos , Modelos Biológicos , Células Procarióticas/metabolismo , Alinhamento de Sequência , Homologia de Sequência
19.
Genet. mol. biol ; 40(4): 751-758, Oct.-Dec. 2017. tab
Artigo em Inglês | LILACS | ID: biblio-892449

RESUMO

Abstract Susceptibility to cancer ensues in individuals carrying malfunctioning DNA repair mechanisms. The impact of Single Nucleotide Polymorphisms (SNPs) in key DNA repair mechanisms on risk for prostate cancer was investigated in this case-control study. Samples consisted of 110 patients with confirmed prostate cancer and 200 unaffected men, from Rio de Janeiro, Brazil. XPD/Lys751Gln (rs13181), APEX1/Asp148Glu (rs1130409), and RAD51/G135C (rs1801320) SNPs were analyzed by PCR-RFLP. Allelic and genotypic frequencies were calculated and compared by Chi-Square test. The association between SNPs and clinical/epidemiological data was considered significant by Odds Ratio analysis, with IC95% and a p-value≤0.05. Only the XPD/Lys751Gln SNP significantly increased susceptibility to disease in southeastern Brazilian men, with p≤0.001 [OR=2.36 (1.46-3.84)], with no association with APEX1 or RAD51 SNPs. Combined XPD+RAD51 SNPs were highly associated with the disease, p≤0.005 [OR=3.40 (1.32-9.20)]. A Chi-Square significant association between XPD/Lys751Gln and Gleason score was also observed (OR=9.31; IC95%=1.19-428.0; p=0.022). Epidemiological inquiries revealed that exposure to pesticides significantly impacted the risk for prostate cancer in this population. DNA repair dysfunctions seem to prevail among workers exposed to chemical byproducts to cancer in this specific tissue. Non-invasive genotyping SNPs may help assessment of prostate cancer risk in environmentally exposed populations.

20.
Astrobiology ; 11(10): 1034-40, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22165956

RESUMO

The haloarchaea Natrialba magadii and Haloferax volcanii, as well as the radiation-resistant bacterium Deinococcus radiodurans, were exposed to vacuum UV (VUV) radiation at the Brazilian Synchrotron Light Laboratory. Cell monolayers (containing 10(5) to 10(6) cells per sample) were prepared over polycarbonate filters and irradiated under high vacuum (10(-5) Pa) with polychromatic synchrotron radiation. N. magadii was remarkably resistant to high vacuum with a survival fraction of (3.77±0.76)×10(-2), which was larger than that of D. radiodurans (1.13±0.23)×10(-2). The survival fraction of the haloarchaea H. volcanii, of (3.60±1.80)×10(-4), was much smaller. Radiation resistance profiles were similar between the haloarchaea and D. radiodurans for fluences up to 150 J m(-2). For fluences larger than 150 J m(-2), there was a significant decrease in the survival of haloarchaea, and in particular H. volcanii did not survive. Survival for D. radiodurans was 1% after exposure to the higher VUV fluence (1350 J m(-2)), while N. magadii had a survival lower than 0.1%. Such survival fractions are discussed regarding the possibility of interplanetary transfer of viable microorganisms and the possible existence of microbial life in extraterrestrial salty environments such as the planet Mars and Jupiter's moon Europa. This is the first work to report survival of haloarchaea under simulated interplanetary conditions.


Assuntos
Deinococcus/efeitos da radiação , Haloferax volcanii/efeitos da radiação , Raios Ultravioleta , Halobacteriaceae/efeitos da radiação , Análise de Sobrevida , Vácuo
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