Both SEPT2 and MLL are down-regulated in MLL-SEPT2 therapy-related myeloid neoplasia

<p>Abstract</p> <p>Background</p> <p>A relevant role of septins in leukemogenesis has been uncovered by their involvement as fusion partners in <it>MLL</it>-related leukemia. Recently, we have established the <it>MLL-SEPT2 </it>gene fusion as the molecular abnormality subjacent to the translocation t(2;11)(q37;q23) in therapy-related acute myeloid leukemia. In this work we quantified <it>MLL </it>and <it>SEPT2 </it>gene expression in 58 acute myeloid leukemia patients selected to represent the major AML genetic subgroups, as well as in all three cases of <it>MLL-SEPT2</it>-associated myeloid neoplasms so far described in the literature.</p> <p>Methods</p> <p>Cytogenetics, fluorescence in situ hybridization (FISH) and molecular studies (RT-PCR, qRT-PCR and qMSP) were used to characterize 58 acute myeloid leukemia patients (AML) at diagnosis selected to represent the major AML genetic subgroups: <it>CBFB-MYH11 </it>(n = 13), <it>PML-RARA </it>(n = 12); <it>RUNX1-RUNX1T1 </it>(n = 12), normal karyotype (n = 11), and <it>MLL </it>gene fusions other than <it>MLL-SEPT2 </it>(n = 10). We also studied all three <it>MLL-SEPT2 </it>myeloid neoplasia cases reported in the literature, namely two AML patients and a t-MDS patient.</p> <p>Results</p> <p>When compared with normal controls, we found a 12.8-fold reduction of wild-type <it>SEPT2 </it>and <it>MLL-SEPT2 </it>combined expression in cases with the <it>MLL-SEPT2 </it>gene fusion (p = 0.007), which is accompanied by a 12.4-fold down-regulation of wild-type <it>MLL </it>and <it>MLL-SEPT2 </it>combined expression (p = 0.028). The down-regulation of <it>SEPT2 </it>in <it>MLL-SEPT2 </it>myeloid neoplasias was statistically significant when compared with all other leukemia genetic subgroups (including those with other <it>MLL </it>gene fusions). In addition, <it>MLL </it>expression was also down-regulated in the group of <it>MLL </it>fusions other than <it>MLL-SEPT2</it>, when compared with the normal control group (p = 0.023)</p> <p>Conclusion</p> <p>We found a significant down-regulation of both <it>SEPT2 </it>and <it>MLL </it>in <it>MLL-SEPT2 </it>myeloid neoplasias. In addition, we also found that <it>MLL </it>is under-expressed in AML patients with <it>MLL </it>fusions other than <it>MLL-SEPT2</it>.</p

Efeitos do treinamento muscular inspiratório em universitários tabagistas e não tabagistas

O hábito de fumar pode reduzir a capacidade aeróbica, aumentar a resistência ao fluxo aéreo e afetar a função dos músculos respiratórios. O objetivo deste estudo foi comparar os efeitos do Treinamento Muscular Inspiratório (TMI) entre dois grupos: tabagistas e não tabagistas. Participaram 44 voluntários universitários, divididos em dois grupos: tabagistas (GT), composto por 20 indivíduos (25,60±7,01 anos) e não tabagistas, constituindo o Grupo Controle (GC), composto por 24 voluntários (24,08±7,52 anos). Ambos os grupos foram submetidos ao TMI, por meio do uso do manovacuômetro aneroide, com duração de 6 semanas, sendo 3 sessões semanais, totalizando 18 sessões. Os resultados mostraram diferença estatisticamente significativa (p<0,05) pós-TMI no GC para as variáveis: Pressão Inspiratória Máxima (PImáx), Pico de Fluxo Expiratório (PFE), Pressão Arterial Média ao repouso (PAM pré-TC6) e Teste de Caminhada de Seis Minutos (TC6). No GT, houve diferença estatisticamente significativa pós-TMI para as variáveis: PImáx, PFE, TC6 e saturação periférica de oxigênio após o TC6 (SpO2 pós-imediata). A comparação das médias das variáveis entre GT e GC mostrou diferença estatisticamente significativa no pós-TMI para as variáveis PImáx e PFE. A variável TC6 não apresentou diferença estatisticamente significativa. Conclui-se que o TMI proporcionou um aumento significativo da força muscular inspiratória, melhora da função pulmonar e melhora do desempenho físico nos indivíduos estudados

Spectroscopic Properties of pigment Li2-xZn1-xPrxTi3O8

Inorganic compounds doped with rare earths (Ce3+, Pr3+, Nd3+, Sm3+, Eu 3+, Gd 3+, Tb 3+, Tm3+) have been used in various applications including light-emitting devices such as fluorescent lamps, cathode ray tubes, lasers and inorganic pigments. In this study, Pr3+ is doped in spinel Li2ZnTi3O8 system and synthesized by the polymeric precursor method, which is based on the process developed by the Pechini, and characterized by X-ray diffraction, UV-visible and CIE-L colorimetric measures * a * b *., in order to study the effect of doping and thermal treatment on its colorimetric properties. With three different samples of Pr3+ doping (0.01; 0.05 and 0.1 mol%) were prepared and calcined at 500°C, 600°C, 700°C, 800°C and 900°C for 4 h. The analysis of X-ray diffraction confirmed the formation of pure phases with spinel structure and average crystallite size of less than 46 nm. It was found that the colorimetric properties ranging from green to red, in accordance with the increase in the concentration of Pr3+ and thermal processing temperature

Perinatal asphyxia: current status and approaches towards neuroprotective strategies, with focus on sentinel proteins

Delivery is a stressful and risky event menacing the newborn. The mother-dependent respiration has to be replaced by autonomous pulmonary breathing immediately after delivery. If delayed, it may lead to deficient oxygen supply compromising survival and development of the central nervous system. Lack of oxygen availability gives rise to depletion of NAD+ tissue stores, decrease of ATP formation, weakening of the electron transport pump and anaerobic metabolism and acidosis, leading necessarily to death if oxygenation is not promptly re-established. Re-oxygenation triggers a cascade of compensatory biochemical events to restore function, which may be accompanied by improper homeostasis and oxidative stress. Consequences may be incomplete recovery, or excess reactions that worsen the biological outcome by disturbed metabolism and/or imbalance produced by over-expression of alternative metabolic pathways. Perinatal asphyxia has been associated with severe neurological and psychiatric sequelae with delayed clinical onset. No specific treatments have yet been established. In the clinical setting, after resuscitation of an infant with birth asphyxia, the emphasis is on supportive therapy. Several interventions have been proposed to attenuate secondary neuronal injuries elicited by asphyxia, including hypothermia. Although promising, the clinical efficacy of hypothermia has not been fully demonstrated. It is evident that new approaches are warranted. The purpose of this review is to discuss the concept of sentinel proteins as targets for neuroprotection. Several sentinel proteins have been described to protect the integrity of the genome (e.g. PARP-1; XRCC1; DNA ligase IIIα; DNA polymerase β, ERCC2, DNA-dependent protein kinases). They act by eliciting metabolic cascades leading to (i) activation of cell survival and neurotrophic pathways; (ii) early and delayed programmed cell death, and (iii) promotion of cell proliferation, differentiation, neuritogenesis and synaptogenesis. It is proposed that sentinel proteins can be used as markers for characterising long-term effects of perinatal asphyxia, and as targets for novel therapeutic development and innovative strategies for neonatal care

Scintillation light detection in the 6-m drift-length ProtoDUNE Dual Phase liquid argon TPC

DUNE is a dual-site experiment for long-baseline neutrino oscillation studies, neutrino astrophysics and nucleon decay searches. ProtoDUNE Dual Phase (DP) is a 6  ×  6  ×  6 m 3 liquid argon time-projection-chamber (LArTPC) that recorded cosmic-muon data at the CERN Neutrino Platform in 2019-2020 as a prototype of the DUNE Far Detector. Charged particles propagating through the LArTPC produce ionization and scintillation light. The scintillation light signal in these detectors can provide the trigger for non-beam events. In addition, it adds precise timing capabilities and improves the calorimetry measurements. In ProtoDUNE-DP, scintillation and electroluminescence light produced by cosmic muons in the LArTPC is collected by photomultiplier tubes placed up to 7 m away from the ionizing track. In this paper, the ProtoDUNE-DP photon detection system performance is evaluated with a particular focus on the different wavelength shifters, such as PEN and TPB, and the use of Xe-doped LAr, considering its future use in giant LArTPCs. The scintillation light production and propagation processes are analyzed and a comparison of simulation to data is performed, improving understanding of the liquid argon properties