Femtosecond two-photon absorption spectroscopy of poly(fluorene) derivatives containing benzoselenadiazole and benzothiadiazole

We have investigated the molecular structure and two-photon absorption (2PA) properties relationship of two push-pull poly(fluorene) derivatives containing benzoselenadiazole and benzothiadiazole units. For that, we have used the femtosecond wavelength-tunable Z-scan technique with a low repetition rate (1 kHz) and an energy per pulse on the order of nJ. Our results show that both 2PA spectra present a strong 2PA (around 600 GM (1 GM = 1×10-50 cm4 .s. photon-1)) band at around 720 nm (transition energy 3.45 eV) ascribed to the strongly 2PA-allowed 1Ag-like → mAg-like transition, characteristic of poly(fluorene) derivatives. Another 2PA band related to the intramolecular charge transfer was also observed at around 900 nm (transition energy 2.75 eV). In both 2PA bands, we found higher 2PA cross-section values for the poly(fluorene) containing benzothiadiazole unit. This outcome was explained through the higher charge redistribution at the excited state caused by the benzothiadiazole group as compared to the benzoselenadiazole and confirmed by means of solvatochromic Stokes shift measurements. To shed more light on these results, we employed the sum-over-states approach within the two-energy level model to estimate the maximum permanent dipole moment change related to the intramolecular charge transfer transition

Effects of proteasome inhibitor MG-132 on the parasite Schistosoma mansoni

Proteasome is a proteolytic complex responsible for intracellular protein turnover in eukaryotes, archaea and in some actinobacteria species. Previous work has demonstrated that in Schistosoma mansoni parasites, the proteasome inhibitor MG-132 affects parasite development. However, the molecular targets affected by MG-132 in S. mansoni are not entirely known. Here, we used expression microarrays to measure the genome-wide changes in gene expression of S. mansoni adult worms exposed in vitro to MG-132, followed by in silico functional analyses of the affected genes using Ingenuity Pathway Analysis (IPA). Scanning electron microscopy was used to document changes in the parasites' tegument. We identified 1,919 genes with a statistically significant (q-value <= 0.025) differential expression in parasites treated for 24 h with MG-132, when compared with control. Of these, a total of 1,130 genes were up-regulated and 790 genes were down-regulated. A functional gene interaction network comprised of MG-132 and its target genes, known from the literature to be affected by the compound in humans, was identified here as affected by MG-132. While MG-132 activated the expression of the 26S proteasome genes, it also decreased the expression of 19S chaperones assembly, 20S proteasome maturation, ubiquitin-like NEDD8 and its partner cullin-3 ubiquitin ligase genes. Interestingly, genes that encode proteins related to potassium ion binding, integral membrane component, ATPase and potassium channel activities were significantly down-regulated, whereas genes encoding proteins related to actin binding and microtubule motor activity were significantly up-regulated. MG132 caused important changes in the worm tegumentpeeling, outbreaks and swelling in the tegument tubercles could be observed, which is consistent with interference on the ionic homeostasis in S. mansoni. Finally, we showed the down-regulation of Bax pro-apoptotic gene, as well as up-regulation of two apoptosis inhibitor genes, IAP1 and BRE1, and in contrast, down-regulation of Apaf-1 apoptotic activator, thus suggesting that apoptosis is deregulated in S. mansoni exposed to MG-132. A considerable insight has been gained concerning the potential of MG-132 as a gene expression modulator, and overall the data suggest that the proteasome might be an important molecular target for the design of new drugs against schistosomiasis.Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, Ribeirao Preto, SP, BrazilUniv Sao Paulo, Dept Bioquim, Inst Quim, Sao Paulo, SP, BrazilAdolfo Lutz Inst, Ctr Parasitol & Micol, Nucleo Enteroparasitas, Sao Paulo, SP, BrazilUniv Franca, Nucleo Pesquisa Ciencias Exatas & Tecnol, Grp Pesquisa Prod Nat, Franca, SP, BrazilInst Butantan, Lab Expressao Genica Eucariotos, Sao Paulo, SP, BrazilUniv Fed Uberlandia, Inst Genet Bioquim, Campus Patos de Minas, Patos De Minas, MG, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Discipline Parasitol, Sao Paulo, SP, BrazilUniv Fed Rio de Janeiro, Inst Biol, Ctr Ciencias & Saude, Rio De Janeiro, RJ, BrazilUniv Fed Sao Paulo, Escola Paulista Med, Dept Microbiol Imunol & Parasitol, Discipline Parasitol, Sao Paulo, SP, BrazilWeb of Scienc

Small forest losses degrade stream macroinvertebrate assemblages in the eastern Brazilian Amazon

Generally, habitat loss and fragmentation negatively affect biota, often in nonlinear ways. Such nonlinear responses suggest the existence of critical limits for habitat loss beyond which taxa experience substantial changes. Therefore, we identified change points for aquatic macroinvertebrate assemblages at both local-riparian and catchment extents in response to a forest-loss gradient in agriculture-altered landscapes of 51 small (1st to 3rd Strahler order) eastern Amazon streams. We used Threshold Indicator Taxa Analysis (TITAN) to identify change points for individual taxa and segmented regression analysis for assemblage richness. Considering the patterns of the cumulative frequency distributions of sum(Z−) maxima across bootstrap replications, peak changes in macroinvertebrate assemblages were at ∼9% (5–95 percentiles = 1–15%) of forest-loss at the catchment extent, and at ∼1.4% (5–95 percentiles = 0–35%) of forest-loss at the local-riparian extent. Although the assemblage change point at the site extent was less than that detected at the catchment extent, the markedly lower percentile range indicates that biotic assemblages are more clearly responsive to forest-loss at the catchment/network-riparian extents than the site extent. For catchment and site extents, segmented regression analysis determined a change point for assemblage richness at 57% and 79% of forest-loss, respectively. This indicates the low capacity of total richness to separate early and synchronous decreases of sensitive taxa from gradual increases of tolerant taxa. Our results also show that it is not enough to focus management and conservation actions on riparian zones, but that conservation strategies should be expanded to entire catchments as well. The sharp decline of sensitive taxa in response to removal of a small portion of forest cover, even at catchment extents, indicates that the Brazilian Forest Code is insufficient for protecting stream macroinvertebrates. Consequently, we recommend strategies to reverse the potential collapse of aquatic biodiversity, particularly through avoiding deforestation and forest degradation, encouraging socio-economic incentives for restoring degraded areas, creating protected areas, and maintaining the current protected areas. We argue that reducing habitat loss should be a top priority for conservation planners in tropical forests because the sensitivity of aquatic biodiversity to removal of riparian forest-cover in Amazon rainforests is higher than previously thought. Therefore, the Forest Code regulatory framework needs complementary regulation that may be achived by more restrictive State and biome policies. © 2019 Elsevier Lt

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein–protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation

Structural studies of Helicase NS3 variants from Hepatitis C virus genotype 3 in virological sustained responder and non-responder patients

<p>Abstract</p> <p>Background</p> <p>About 130 million people are infected with the hepatitis C virus (HCV) worldwide, but effective treatment options are not yet available. One of the most promising targets for antiviral therapy is nonstructural protein 3 (NS3). To identify possible changes in the structure of NS3 associated with virological sustained response or non-response of patients, a model was constructed for each helicase NS3 protein coding sequence. From this, the goal was to verify the interaction between helicases variants and their ligands.</p> <p>Findings</p> <p>Evidence was found that the NS3 helicase portion of non-responder patients contained substitutions in its ATP and RNA binding sites. K210E substitution can cause an imbalance in the distribution of loads, leading to a decrease in the number of ligations between the essential amino acids required for the hydrolysis of ATP. W501R substitution causes an imbalance in the distribution of loads, leading and forcing the RNA to interact with the amino acid Thr269, but not preventing binding of ribavirin inhibitor.</p> <p>Conclusions</p> <p>Useful information is provided on the genetic profiling of the HCV genotype 3, specifically the coding region of the NS3 protein, improving our understanding of the viral genome and the regions of its protein catalytic site.</p

Distinct patterns of somatic alterations in a lymphoblastoid and a tumor genome derived from the same individual

Although patterns of somatic alterations have been reported for tumor genomes, little is known on how they compare with alterations present in non-tumor genomes. A comparison of the two would be crucial to better characterize the genetic alterations driving tumorigenesis. We sequenced the genomes of a lymphoblastoid (HCC1954BL) and a breast tumor (HCC1954) cell line derived from the same patient and compared the somatic alterations present in both. The lymphoblastoid genome presents a comparable number and similar spectrum of nucleotide substitutions to that found in the tumor genome. However, a significant difference in the ratio of non-synonymous to synonymous substitutions was observed between both genomes (P = 0.031). Protein–protein interaction analysis revealed that mutations in the tumor genome preferentially affect hub-genes (P = 0.0017) and are co-selected to present synergistic functions (P < 0.0001). KEGG analysis showed that in the tumor genome most mutated genes were organized into signaling pathways related to tumorigenesis. No such organization or synergy was observed in the lymphoblastoid genome. Our results indicate that endogenous mutagens and replication errors can generate the overall number of mutations required to drive tumorigenesis and that it is the combination rather than the frequency of mutations that is crucial to complete tumorigenic transformation

Balneotherapy is a potential risk factor for Pseudomonas aeruginosa colonization

The practice of immersion in burn patient has been abandoned in many parts of the world but in Brazil it is still common. The aim of this study was to ascertain if balneotherapy is a risk factor for Pseudomonas aeruginosa colonization in thermally injured patients. Eighteen patients from a Burn Center were studied for 14 weeks for Pseudomonas aeruginosa. Samples were collected by swabbing the exudate of wounds, before and after giving bath to the patients and from balneotherapy table. Pulsed-field gel electrophoresis was used to determine bacterial genetic relatedness. Thirty-seven P. aeruginosa isolates were detected from 292 swabs collected from patients&apos; burn surface area and from the balneotherapy table. Profile analysis of P. aeruginosa DNA fragmentation showed 10 clones among the 37 strains analyzed. Type A is the most prevalent clone, with 23 strains distributed into eight subtypes. These were present in the swabs collected, before and after the patients&apos; bath, from the surface of the bath table, suggesting that there was cross-contamination between the patients in different ways. This work demonstrates that balneotherapy is a risk factor in the Burn Center studied, because the same clone was found among P. aeruginosa isolates collected at various points and times. Uniterms: Pseudomonas aeruginosa/colonization. Burn patients. Balneotherapy. PFGE. A prática de balneotarapia em paciente queimado foi abandonada em muitas partes do mundo, mas no Brasil ainda é comum. O objetivo deste estudo foi verificar se a balneoterapia é um fator de risco para a colonização por Pseudomonas aeruginosa em pacientes queimados. Dezoito pacientes internados em um Centro de Queimadura (CQ) foram acompanhados por 14 semanas. Amostras foram coletadas do exsudato de feridas, antes e depois do banho dos pacientes e também da mesa onde a balneoterapia foi realizada. A relação genética entre as cepas de P. aeruginosa foi determinada pela electroforese em gel de campo pulsado. Trinta e sete cepas foram detectadas a partir de 292 swabs coletados de área de superfície das feridas dos pacientes e da mesa de balneoterapia. Análise de fragmentação do DNA das 37 P. aeruginosa mostrou a existência de 10 clones. O tipo A foi o clone mais prevalente, com 23 cepas distribuídas em oito subtipos. Estas estavam presentes nas lesões dos pacientes antes e após o banho e na mesa onde o banho foi realizado, sugerindo contaminação cruzada inter e intra-pacientes e pacientes e mesa de banho. Este trabalho mostra que a balneoterapia é um fator de risco para colonização por P. aeruginosa, no CQ estudado, pois um mesmo clone da bactéria foi encontrado nos isolados coletados em vários pontos e épocas diferentes. Unitermos: Pseudomonas aeruginosa/colonização. Pacientes queimados/tratamento. Balneoterapia. Eletroforese em campo pulsado