Photoactivatable Ruthenium Complexes Containing Minimal Straining Benzothiazolyl-1,2,3-triazole Chelators for Cancer Treatment.

Ruthenium(II) complexes containing diimine ligands have contributed to the development of agents for photoactivated chemotherapy. Several approaches have been used to obtain photolabile Ru(II) complexes. The two most explored have been the use of monodentate ligands and the incorporation of steric effects between the bidentate ligands and the Ru(II). However, the introduction of electronic effects in the ligands has been less explored. Herein, we report a systematic experimental, theoretical, and photocytotoxicity study of a novel series of Ru(II) complexes Ru1-Ru5 of general formula [Ru(phen)2(N∧N')]2+, where N∧N' are different minimal strained ligands based on the 1-aryl-4-benzothiazolyl-1,2,3-triazole (BTAT) scaffold, being CH3 (Ru1), F (Ru2), CF3 (Ru3), NO2 (Ru4), and N(CH3)2 (Ru5) substituents in the R4 of the phenyl ring. The complexes are stable in solution in the dark, but upon irradiation in water with blue light (λex = 465 nm, 4 mW/cm2) photoejection of the ligand BTAT was observed by HPLC-MS spectrometry and UV-vis spectroscopy, with t1/2 ranging from 4.5 to 14.15 min depending of the electronic properties of the corresponding BTAT, being Ru4 the less photolabile (the one containing the more electron withdrawing substituent, NO2). The properties of the ground state singlet and excited state triplet of Ru1-Ru5 have been explored using density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations. A mechanism for the photoejection of the BTAT ligand from the Ru complexes, in H2O, is proposed. Phototoxicity studies in A375 and HeLa human cancer cell lines showed that the new Ru BTAT complexes were strongly phototoxic. An enhancement of the emission intensity of HeLa cells treated with Ru5 was observed in response to increasing doses of light due to the photoejection of the BTAT ligand. These studies suggest that BTAT could serve as a photocleavable protecting group for the cytotoxic bis-aqua ruthenium warhead [Ru(phen)2(OH2)2]2+.

The ncBAF Complex Regulates Transcription in AML Through H3K27ac Sensing by BRD9.

The non-canonical BAF complex (ncBAF) subunit BRD9 is essential for acute myeloid leukemia (AML) cell viability but has an unclear role in leukemogenesis. Because BRD9 is required for ncBAF complex assembly through its DUF3512 domain, precise bromodomain inhibition is necessary to parse the role of BRD9 as a transcriptional regulator from that of a scaffolding protein. To understand the role of BRD9 bromodomain function in regulating AML, we selected a panel of five AML cell lines with distinct driver mutations, disease classifications, and genomic aberrations and subjected these cells to short-term BRD9 bromodomain inhibition. We examined the bromodomain-dependent growth of these cell lines, identifying a dependency in AML cell lines but not HEK293T cells. To define a mechanism through which BRD9 maintains AML cell survival, we examined nascent transcription, chromatin accessibility, and ncBAF complex binding genome-wide after bromodomain inhibition. We identified extensive regulation of transcription by BRD9 bromodomain activity, including repression of myeloid maturation factors and tumor suppressor genes, while standard AML chemotherapy targets were repressed by inhibition of the BRD9 bromodomain. BRD9 bromodomain activity maintained accessible chromatin at both gene promoters and gene-distal putative enhancer regions, in a manner that qualitatively correlated with enrichment of BRD9 binding. Furthermore, we identified reduced chromatin accessibility at GATA, ETS, and AP-1 motifs and increased chromatin accessibility at SNAIL-, HIC-, and TP53-recognized motifs after BRD9 inhibition. These data suggest a role for BRD9 in regulating AML cell differentiation through modulation of accessibility at hematopoietic transcription factor binding sites. SIGNIFICANCE: The bromodomain-containing protein BRD9 is essential for AML cell viability, but it is unclear whether this requirement is due to the protein's role as an epigenetic reader. We inhibited this activity and identified altered gene-distal chromatin regulation and transcription consistent with a more mature myeloid cell state.

FACT regulates pluripotency through proximal and distal regulation of gene expression in murine embryonic stem cells.

BACKGROUND: The FACT complex is a conserved histone chaperone with critical roles in transcription and histone deposition. FACT is essential in pluripotent and cancer cells, but otherwise dispensable for most mammalian cell types. FACT deletion or inhibition can block induction of pluripotent stem cells, yet the mechanism through which FACT regulates cell fate decisions remains unclear. RESULTS: To explore the mechanism for FACT function, we generated AID-tagged murine embryonic cell lines for FACT subunit SPT16 and paired depletion with nascent transcription and chromatin accessibility analyses. We also analyzed SPT16 occupancy using CUT&RUN and found that SPT16 localizes to both promoter and enhancer elements, with a strong overlap in binding with OCT4, SOX2, and NANOG. Over a timecourse of SPT16 depletion, nucleosomes invade new loci, including promoters, regions bound by SPT16, OCT4, SOX2, and NANOG, and TSS-distal DNaseI hypersensitive sites. Simultaneously, transcription of Pou5f1 (encoding OCT4), Sox2, Nanog, and enhancer RNAs produced from these genes' associated enhancers are downregulated. CONCLUSIONS: We propose that FACT maintains cellular pluripotency through a precise nucleosome-based regulatory mechanism for appropriate expression of both coding and non-coding transcripts associated with pluripotency.

Ru(ii) photosensitizers competent for hypoxic cancers via green light activation.

A family of five heteroleptic complexes [Ru(C^N)(N^N)2][PF6] (HC^N = methyl 1-butyl-2-arylbenzimidazolecarboxylate; N^N = polypyridine) has been synthesized to act as biologically-compatible green light photosensitizers (PSs) with phototherapeutic indexes (PIs) up to higher than 700 under hypoxia (2% O2) in HeLa cancer cells under short time of irradiation.

Amino-Functionalized Mesoporous Silica Nanoparticle-Encapsulated Octahedral Organoruthenium Complex as an Efficient Platform for Combatting Cancer.

In the process of synthesis of a new drug, as important as the drug itself is the formulation used, because the same compound can present a very different efficacy depending on how it is administered. In this work, we demonstrate how the antitumor capacity of a new octahedral organoruthenium complex, [Ru(ppy-CHO)(phen)2][PF6] is affected by its encapsulation in different types of mesoporous silica nanoparticles. The interactions between the Ru complex and the silica matrix and how these interactions are affected at two different pHs (7.4 and 5.4, mimicking physiological and endolysosomal acidic conditions, respectively) have been studied. The encapsulation has also been shown to affect the induction of apoptosis and necrosis and progression of the cell cycle compared to the free drug. The encapsulation of the Ru complex in nanoparticles functionalized with amino groups produced very high anticancer activity in cancer cells in vitro, especially against U87 glioblastoma cells, favoring cellular internalization and significantly increasing the anticancer capacity of the initial non-encapsulated Ru complex.

A catalyst for transforming health systems and person-centred care: Canadian national position statement on patient-reported outcomes.

Background: Patient-reported outcomes (pros) are essential to capture the patient's perspective and to influence care. Although pros and pro measures are known to have many important benefits, they are not consistently being used and there is there no Canadian pros oversight. The Position Statement presented here is the first step toward supporting the implementation of pros in the Canadian health care setting. Methods: The Canadian pros National Steering Committee drafted position statements, which were submitted for stakeholder feedback before, during, and after the first National Canadian Patient Reported Outcomes (canpros) scientific conference, 14-15 November 2019 in Calgary, Alberta. In addition to the stakeholder feedback cycle, a patient advocate group submitted a section to capture the patient voice. Results: The canpros Position Statement is an outcome of the 2019 canpros scientific conference, with an oncology focus. The Position Statement is categorized into 6 sections covering 4 theme areas: Patient and Families, Health Policy, Clinical Implementation, and Research. The patient voice perfectly mirrors the recommendations that the experts reached by consensus and provides an overriding impetus for the use of pros in health care. Conclusions: Although our vision of pros transforming the health care system to be more patient-centred is still aspirational, the Position Statement presented here takes a first step toward providing recommendations in key areas to align Canadian efforts. The Position Statement is directed toward a health policy audience; future iterations will target other audiences, including researchers, clinicians, and patients. Our intent is that future versions will broaden the focus to include chronic diseases beyond cancer.

Super-resolution imaging reveals the evolution of higher-order chromatin folding in early carcinogenesis.

Genomic DNA is folded into a higher-order structure that regulates transcription and maintains genomic stability. Although progress has been made on understanding biochemical characteristics of epigenetic modifications in cancer, the in-situ higher-order folding of chromatin structure during malignant transformation remains largely unknown. Here, using optimized stochastic optical reconstruction microscopy (STORM) for pathological tissue (PathSTORM), we uncover a gradual decompaction and fragmentation of higher-order chromatin folding throughout all stages of carcinogenesis in multiple tumor types, and prior to tumor formation. Our integrated imaging, genomic, and transcriptomic analyses reveal functional consequences in enhanced transcription activities and impaired genomic stability. We also demonstrate the potential of imaging higher-order chromatin disruption to detect high-risk precursors that cannot be distinguished by conventional pathology. Taken together, our findings reveal gradual decompaction and fragmentation of higher-order chromatin structure as an enabling characteristic in early carcinogenesis to facilitate malignant transformation, which may improve cancer diagnosis, risk stratification, and prevention.

Physical approach for a quantitative analysis of the phytosterols in free phytosterol-oil blends by X-ray Rietveld method.

This study investigates and compares the thermal phase transition and crystallization characteristics of a commercial food grade free phytosterol blend (FP) with a stigmasterol analytical standard (SS), the FP behavior in a food model system after its addition to high oleic sunflower oil (HOSO). The properties of the FP:HOSO blends were studied by differential scanning calorimetry, solid content, crystal morphology, and X-ray diffraction (XRD) measurements. The Rietveld method (RM) was applied associated with the XRD measurements to support phase analysis and the study of crystallinity degree. The materials were also characterized by means of chemical composition, such as fatty acids and triacylglycerol profiles, for HOSO, and phytosterol profile, for FP. Regarding phase behavior and crystallinity properties, FP has very similar characteristics to SS. The thermal behavior of FP:HOSO blends has two characteristic peaks, one from FP and the other from HOSO. The similarity reported in the literature between the diffraction pattern of FP and pure phytosterols is a positive characteristic for FP. A high FP concentration resulted in high supersaturation and thus the formation of small crystals. The incorporation of HOSO reduced of the large agglomeration of FP crystals and the dispersion crystalline aggregates (spherulites) of FP crystals. The application of RM in FP:HOSO blends to quantify the crystalline and amorphous phases was successfully used. The application has provided the expected value for these phases, according to the same experimental mass ratio of the blends, thereby validating the applicability of this approach in this type of material.

New half-sandwich ruthenium(ii) complexes as proteosynthesis inhibitors in cancer cells.

Half-sandwich ruthenium(ii) complexes [(η6-p-cymene)Ru(C^N)-(X)]0/+ (X = Cl, py or 4-NMe2-py) containing a cyclometalated 2-ppy or 1-ppz with a non-coordinated CHO group as a handle for further functionalization have been synthesized to achieve selective cytotoxicity to cancer cells, the more potent compounds acting as proteosynthesis inhibitors; this is a new mode of action for half-sandwich metal complexes.

Avaliação dos níveis séricos de hormônios tireoidianos em araras (Ara spp) pelo método de quimioluminescência / Evaluation of serum levels of thyroid hormones in macaws (Ara spp) by chemiluminescence

Este trabalho investigou a eficiência do método de quimioluminescência para obtenção das concentrações séricas de hormônios tireoidianos em 23 exemplares de araras [Ara ararauna (n=12) e Ara chloropterus (n=11)], de ambos os sexos [machos (n=11) e fêmeas (n=12)], mantidas em cativeiro. Os valores de T4 total, T4 livre, T3 livre e TSH variaram, respectivamente, de 0,3 a 2,5µg/dL (média=0,94µg/dL), 0,11 a 0,46ɳg/dL (média=0,28ɳg/dL), 1,46 a 3,59pg/mL (média= 2,42pg/mL) e 0,01 a 0,12µUI/mL (média=0,04µUI/mL). Houve interação entre espécie e sexo (P<0,05) sobre as concentrações de T4 total: os machos possuem maiores valores do que as fêmeas de Ara ararauna, enquanto as fêmeas de Ara chloropterus dispõem de níveis mais altos do que os machos desta espécie. Efeito de sexo não foi observado (P>0,05) para os valores de T4 livre, T3 livre e TSH, mas o efeito de espécie foi constatado (P<0,05) para as concentrações de T3 livre. Neste caso, as concentrações de T3 livre são menores em Ara ararauna do que em Ara chloropterus. Os intervalos de referência obtidos sugerem que é possível mensurar as concentrações séricas de hormônios tireoidianos em araras pelo método de quimioluminescência, devendo-se considerar variações relevantes entre diferentes espécies e sexos.(AU)

This paper investigated the efficiency of chemiluminescence in obtaining serum concentrations of thyroid hormones in twenty-three macaws kept in captivity, from two sexes [male (n=10) and female (n=12)] and two species [Ara ararauna (n=12) and Ara chloropterus (n=11)]. Reference intervals for the hormones sampled were indicated and the effects of species and sex on these values were analyzed. Concentration values of total T4, free T4, free T3 and TSH varied respectively from 0,3 to 2,5µg/dL (average =0,94µg/dL), 0,11 - 0,46ɳg/dL (average = 0,28ɳg/dL), 3,59 - 1,46pg/mL (average =2,42pg/mL), and 0,01 - 0,12µUI/mL (average= 0,04µUI/mL). There was interaction between species and sex (P<0.05) on total T4 concentrations. Males had higher values than females in Ara ararauna, while females had higher values than males in Ara chloropterus. Sex effect was not observed (P>0.05) for concentrations of free T4, free T3 and TSH, but species effect was observed (P<0.05) for free T3 concentrations. In this case, concentrations of free T3 were lower in Ara ararauna than in Ara chloropterus. The results of this study suggest that it is possible to measure serum concentration of thyroid hormones in macaws by means of chemiluminescence method, as long as relevant variations between different species and sexes are taken into account.(AU)

Allantoin as an independent marker associated with carotid intima-media thickness in subclinical atherosclerosis

Allantoin is the main product of uric acid oxidation and was found to be augmented in atherosclerotic plaque in human autopsy and in animal models of atherosclerosis. Uric acid is abundant in human plasma and is prone to oxidation in inflammatory conditions such as atherosclerosis. In this study, we found a significant increase in plasma uric acid (P=0.002) and allantoin (P=0.025) in participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) that presented common carotid intima-media thickness (c-IMT) within the 75th percentile (c-IMT≥P75). Multiple linear regression showed an association of c-IMT with uric acid (β=0.0004, P=0.014) and allantoin (β=0.018, P=0.008). This association was independent of age, the traditional risk factor LDL/HDL ratio, and non-traditional risk factors: pulse pressure, neck circumference, and the inflammatory marker myeloperoxidase. The independent and strong association of allantoin with c-IMT shows that it might be a useful marker, along with other traditional risk factors, to evaluate an early stage of atherosclerosis.

Avaliação das técnicas de imunodifusão em gel de ágar, ensaio imunoenzimático indireto e reação em cadeia da polimerase no diagnóstico da brucelose ovina / Evaluation of technical, immunodiffusion agar gel, enzyme-linked immunosorbent assay and polymerase chain reaction in the diagnosis of ovine brucellosis

A brucelose na espécie ovina tem recebido destaque, uma vez que se trata de uma enfermidade que acomete o sistema reprodutivo dos animais, provocando sério comprometimento no setor produtivo. Dessa forma, objetivou-se a avaliação de três métodos para o diagnóstico da brucelose ovina: o ensaio imunoenzimático indireto (ELISAi), a técnica imunodifusão em gel de ágar (IDGA) e a reação em cadeia da polimerase (PCR). Para tanto, utilizaram-se 211 amostras de sangue de ovinos oriundos de propriedades de nove municípios da microrregião homogênea de Teresina, Piauí. As 211 amostras de sangue foram submetidas aos testes sorológicos e à PCR, visando detectar anticorpos anti-B. ovis e DNA de Brucella ovis, respectivamente. Foram obtidos resultados positivos nos testes sorológicos, sendo 36 (17,06%) positivos no teste IDGA e sete (3,31%) positivos no teste ELISAi, contudo não houve resultados positivos na técnica de PCR. Dos métodos de diagnóstico utilizados neste estudo, o teste IDGA foi o que apresentou melhor desempenho na detecção de animais reagentes, quando comparado ao teste ELISAi e à PCR em amostras de sangue, e o percentual de animais soropositivos sugere uma ampla distribuição de ovinos infectados por Brucella ovis na região em estudo, o que pode causar prejuízos aos produtores.(AU)

Brucellosis in sheep has received a major focus, since it is a disease that affects the reproductive system of animals, causing serious impairment in the productive sector. Thus, three methods for the diagnosis of ovine brucellosis were evaluated as goal, the indirect Linked Immunosorbent Assay (ELISAi) test, the Immunodiffusion Agar Gel (AGID) technique and the Polymerase Chain Reaction (PCR). Therefore, we used 211 sheep blood samples from properties of nine municipalities of the homogeneous micro-region of Teresina, Piaui. The 211 blood samples were subjected to serologic testing and PCR to detect anti-B. ovis antibodies, and Brucella ovis DNA, respectively. Positive results in serological tests were obtained, 36 (17%) positive in the AGID test and seven (3.3%) positive to the ELISAi test, however, there were no positive results in the PCR technique. Of the diagnostic methods used in this study, the AGID test was the one that presented the best performance in the detection of reactive animals, when compared to ELISAi and PCR in blood samples and, the percentage of seropositive animals suggests a wide distribution of Brucella ovis infected sheep in the study region and could cause loss to producers.(AU)

Measurements of femoral angles, femur length, and hip width in cat radiographs / Medidas dos ângulos femorais, comprimento do fêmur e largura do quadril em radiografias de gatos

Femoral angle, femur length, and hip width were measured in radiographs of 92 intact domestic cats, males and females of mixed breed from the Center for Zoonosis Control of the Federal District. The animals showed no trauma, orthopedic diseases or angular deformities and had closed physeal lines. Accordingly, we measured aLPFA (anatomical lateral proximal femoral angle, aLDFA (anatomical lateral distal femoral angle), mLPFA (mechanical lateral proximal femoral angle), mLDFA (mechanical lateral distal femoral angle), IA (femoral inclination angle), FL (femur length) and HW (hip width) using ventrodorsal radiographs, with both hindlimbs in a single exposure to an X-ray beam centered on the hip. The mean values of the variables were: mLPFA: 82.5±3.62°; aLPFA: 80.1±4.29°; mLDFA: 96.1±3.51° (males) and 97.3±2.05° (females); aLDFA: 94,3±3.43°; IA: 136.6±3.86°; FL: 12.9±0.55cm (males) and 13.4±0.66cm (females); and HW: 3.1cm±0.23 (males) and 3.5±0.26cm (females). These values will serve as a reference for the diagnosis of angular deformities and as support for planning corrective osteotomies in domestic cats.(AU)

Foram realizadas mensurações radiográficas dos ângulos femorais e medidas lineares do quadril e do fêmur em 92 gatos domésticos, machos e fêmeas, SRD, oriundos do Centro de Controle de Zoonoses do Distrito Federal, livres de traumas, doenças ortopédicas e deformidades angulares em membros pélvicos, portadores de linhas fiseais fechadas, não castrados. Para tanto, foram obtidos os ângulos aLPFA (ângulo anatômico lateral proximal do fêmur), aLDFA (ângulo anatômico lateral distal do fêmur), mLPFA (ângulo mecânico lateral proximal do fêmur), mLDFA (ângulo mecânico lateral distal do fêmur), AI (ângulo de inclinação do fêmur), CF (comprimento femoral) e LQ (largura de quadril), empregando radiografias em projeções ventrodorsais, com ambos os membros em uma única exposição ao feixe de raios-X, centrada no quadril. Após a apuração dos resultados, os valores médios obtidos foram: mLPFA: 82,5°±3,62, aLPFA: 80,1°±4,29; mLDFA: 96,1°±3.51 (machos) e 97,3°±2,05 (fêmeas), aLDFA: 94,3,6°±3,43; AI: 136,6°±3,86; CF: 136,6°±3,86; 12,9cm±0,55 (machos) e 13,4cm±0,66 (fêmeas) e LQ: 3,1cm±0,23 (machos) e 3,5cm±0,26 (fêmeas), respectivamente. Esses valores servem como referenciais para diagnósticos de deformidades angulares e apoio para planejamento de osteotomias corretivas em felinos domésticos.(AU)

Structure, Spectra, and DFT Simulation of Nickel Benzazolate Complexes with Tris(2-aminoethyl)amine Ligand.

Benzazolate complexes of Ni(II), [Ni(pbz)(tren)]ClO4 (pbz = 2-(2'-hydroxyphenyl)-benzimidazole (pbm), 1, 2-(2'-hydroxyphenyl)-benzoxazole (pbx), 2, 2-(2'-hydroxyphenyl)-benzothiazole (pbt), 3; tren = tris(2-aminoethyl)amine), are prepared by self-assembly reaction and structurally characterized. Theoretical DFT simulations are carried out to reproduce the features of their crystal structures and their spectroscopic and photophysic properties. The three complexes are moderately luminescent at room temperature both in acetonitrile solution and in the solid state. The simulations indicate that the absorption spectrum is dominated by two well-defined transitions, and the electronic density concentrates in three MOs around the benzazole ligands. The Stokes shifts of the emission spectra of complexes 1-3 are determined by optimizing the electronic excited state.

Cystic fibrosis in Afro-Brazilians: XK haplotypes analysis supports the European origin of p.F508del mutation.

Cystic fibrosis (CF) is a common autosomal recessive disorder, being the p.F508del the most frequent mutation. Also, a nearby restriction fragment length polymorphism (RFLP) named XK (KM19 and XV2C) is non-randomly associated with specific CF alleles. Our aim was to analyze the occurrence of the p.F508del mutation and XK haplotypes in Afro-Brazilians CF patients and controls, since these data is available for the other two main ethnic groups found in Brazil (Euro-Brazilians and Brazilian Amerindians), contributing for the whole comprehension of these haplotypes in the Brazilian population. A total of 103 patients and 54 controls were studied. PCR and PCR-RFLP methodologies were used to identify the presence of the p.F508del and the XK haplotype in the subjects. The combined data show that 84.2% of p.F508del mutation is associated with haplotype B and only 15.8% with haplotype A; no other haplotypes were found to be associated with this mutation. Our data suggest that the occurrence of p.F508del mutation and haplotype B in Afro-Brazilian patients occurs probably due to admixture with Euro-descendants. Therefore this mutation and haplotype could be used as a admixture marker.

CD8+ T Cells from Human Neonates Are Biased toward an Innate Immune Response.

To better understand why human neonates show a poor response to intracellular pathogens, we compared gene expression and histone modification profiles of neonatal naive CD8+ T cells with that of their adult counterparts. We found that neonatal lymphocytes have a distinct epigenomic landscape associated with a lower expression of genes involved in T cell receptor (TCR) signaling and cytotoxicity and a higher expression of genes involved in the cell cycle and innate immunity. Functional studies corroborated that neonatal CD8+ T cells are less cytotoxic, transcribe antimicrobial peptides, and produce reactive oxygen species. Altogether, our results show that neonatal CD8+ T cells have a specific genetic program biased toward the innate immune response. These findings will contribute to better diagnosis and management of the neonatal immune response.

Effects of dispersed oil exposure on biomarker responses and growth in juvenile wolfish Anarhichas denticulatus.

This study evaluated the sensitivity of the wolfish Anarhichas denticulatus exposed to crude oil, comparing the effects of mechanically dispersed versus chemically dispersed oil using sub-lethal endpoints. To test the toxicity of this controversial technique, two experiments involving exposure of the organisms for 48 h were conducted. The first experiment assessed the effects of oil exposure on biomarker responses. The second experiment monitored the growth of juveniles over 5 weeks after exposure. Overall, this study demonstrated that polycyclic aromatic hydrocarbon (PAH) biliary metabolites, ethoxyresorufin-O-deethylase (EROD), and acetylcholinesterase (AChE) are appropriate biomarkers to assess exposure of A. denticulatus. Growth rate, both in length and weight, was significantly higher in control compared to oil exposure treatments. The lack of differences between chemically and mechanically dispersed oils in biomarker response and growth suggests that dispersant application is no more toxic than the natural oil dispersion. The results indicate the potential for population-level effects resulting from exposure to oil.

Different expression patterns of LGALS1 and LGALS3 in polycythemia vera, essential thrombocythemia and primary myelofibrosis.

Despite all the knowledge, the cellular and molecular mechanisms involved in myeloproliferative neoplasm (MPN) pathophysiology remain unclear. Authors have shown galectin-1 (Gal-1) and 3 playing roles in tumour angiogenesis and fibrosis, which were correlated with poor prognosis in patients with MPN. In the present study LGALS1 and LGALS3 were differently expressed between polycythemia vera, essential thrombocythemia (ET) and primary myelofibrosis (PMF) diseases. Increased LGALS3 expression was associated with a negative JAK2 V617F status mutation in leucocytes from PMF but not in patients with ET without this mutation. However, a positive Janus kinase 2 (JAK2) V617F cell line established from patients with ET (SET-2 cells) when treated with JAK inhibitor presented high levels of LGALS3. Additionally, high LGALS1 expression was found in CD34(+) cells but not in leucocytes from patients with PMF, in absence of JAK2 V617F mutation, and also in SET-2 cells treated with JAK inhibitor. Thus, our findings indicate that differential expression of LGALS1 and/or LGALS3 in patients with MPN is linked with JAK2 V617F status mutation in these diseases and state of cell differentiation.

Host preference, population growth and injuries assessment of Polyphagotarsonemus latus (banks) (ACARI: Tarsonemidae) on Capsicum annuum L. Genotypes.

Despite the continued efforts on the search for different genotypes, Capsicum annuum (L.) is quite susceptible to attack by pest arthropods, especially the broad mite Polyphagotarsonemus latus Banks. Thus, the host preference, population growth and the injuries assessment of P. latus was studied on six C. annuum genotypes used in Brazil (Atlantis, California Wonder, Impact, Palloma, Rubia and Tendence). Host preference was accessed in choice tests, pairing the several genotypes, and the population growth was observed through non-choice tests in laboratory. The injuries assessments were evaluated in the greenhouse, comparing the injury level among the six genotypes. The results indicate that California Wonder and Palloma genotypes were more preferred by P. latus, and Impact and Tendence were less preferred. P. latus presented positive population growth rates (ri) on all the genotypes, however, Palloma and California Wonder showed the highest values of population growth rate (ri = 0.344 and ri = 0.340, respectively), while Impact had the lowest value (ri = 0.281). All the evaluated C. annuum genotypes showed low tolerance to P. latus and exhibited several injuries, but there was no statistical difference between them. California Wonder had the highest average number of mites/leaf (57.15), while Impact and Tendence obtained the lowest values (36.67 and 35.12, respectively) at the end of the evaluation period. The total average of injuries notes at the end of the bioassay did not differ between the genotypes. The number of mites/leaf was growing for the injury scale to the note 3.0, but when the injury scale approached the note 4.0, there was observed a decrease in the number of mites/leaf for all the genotypes.

Saddle antenna radio frequency ion sources.

Existing RF ion sources for accelerators have specific efficiencies for H(+) and H(-) ion generation ∼3-5 mA/cm(2) kW, where about 50 kW of RF power is typically needed for 50 mA beam current production. The Saddle Antenna (SA) surface plasma source (SPS) described here was developed to improve H(-) ion production efficiency, reliability, and availability. In SA RF ion source, the efficiency of positive ion generation in the plasma has been improved to 200 mA/cm(2) kW. After cesiation, the current of negative ions to the collector was increased from 1 mA to 10 mA with RF power ∼1.5 kW in the plasma (6 mm diameter emission aperture) and up to 30 mA with ∼4 kW RF. Continuous wave (CW) operation of the SA SPS has been tested on the test stand. The general design of the CW SA SPS is based on the pulsed version. Some modifications were made to improve the cooling and cesiation stability. CW operation with negative ion extraction was tested with RF power up to ∼1.2 kW in the plasma with production up to Ic = 7 mA. A stable long time generation of H(-) beam without degradation was demonstrated in RF discharge with AlN discharge chamber.