Review of The Most Reluctant Convert (play)

Review of The Most Reluctant Convert, based on the book Surprised by Joy by C. S. Lewis, adapted by and starring Max McLean. Colorado Springs, Colorado: Pikes Peak Center, 29 June 2019

Type III restriction endonuclease EcoP15I is a heterotrimeric complex containing one Res subunit with several DNA-binding regions and ATPase activity

For efficient DNA cleavage, the Type III restriction endonuclease EcoP15I communicates with two inversely oriented recognition sites in an ATP-dependent process. EcoP15I consists of methylation (Mod) and restriction (Res) subunits forming a multifunctional enzyme complex able to methylate or to cleave DNA. In this study, we determined by different analytical methods that EcoP15I contains a single Res subunit in a Mod2Res stoichiometry. The Res subunit comprises a translocase (Tr) domain carrying functional motifs of superfamily 2 helicases and an endonuclease domain with a PD..D/EXK motif. We show that the isolated Tr domain retains ATP-hydrolyzing activity and binds single- and double-stranded DNA in a sequence-independent manner. To localize the regions of DNA binding, we screened peptide arrays representing the entire Res sequence for their ability to interact with DNA. We discovered four DNA-binding regions in the Tr domain and two DNA-binding regions in the endonuclease domain. Modelling of the Tr domain shows that these multiple DNA-binding regions are located on the surface, free to interact with DNA. Interestingly, the positions of the DNA-binding regions are conserved among other Type III restriction endonucleases

Genome-wide association study identifies susceptibility loci for acute myeloid leukemia

Acute myeloid leukemia (AML) is a hematological malignancy with an undefined heritable risk. Here we perform a meta-analysis of three genome-wide association studies, with replication in a fourth study, incorporating a total of 4018 AML cases and 10488 controls. We identify a genome-wide significant risk locus for AML at 11q13.2 (rs4930561; P = 2.15 × 10-8; KMT5B). We also identify a genome-wide significant risk locus for the cytogenetically normal AML sub-group (N = 1287) at 6p21.32 (rs3916765; P = 1.51 × 10-10; HLA). Our results inform on AML etiology and identify putative functional genes operating in histone methylation (KMT5B) and immune function (HLA)

Down syndrome is an oxidative phosphorylation disorder

Down syndrome is the most common genomic disorder of intellectual disability and is caused by trisomy of chromosome 21. Several genes in this chromosome repress mitochondrial biogenesis. The goal of this study was to evaluate whether early overexpression of these genes may cause a prenatal impairment of oxidative phosphorylation negatively affecting neurogenesis. Reduction in the mitochondrial energy production and a lower mitochondrial function have been reported in diverse tissues or cell types, and also at any age, including early fetuses, suggesting that a defect in oxidative phosphorylation is an early and general event in Down syndrome individuals. Moreover, many of the medical conditions associated with Down syndrome are also frequently found in patients with oxidative phosphorylation disease. Several drugs that enhance mitochondrial biogenesis are nowadays available and some of them have been already tested in mouse models of Down syndrome restoring neurogenesis and cognitive defects. Because neurogenesis relies on a correct mitochondrial function and critical periods of brain development occur mainly in the prenatal and early neonatal stages, therapeutic approaches intended to improve oxidative phosphorylation should be provided in these periods.Funding sources: This work was supported by grants from Instituto de Salud Carlos III [FIS-PI17/00021, FIS-PI17/00166]; Fundación Mutua Madrileña [MMA17/01]; Precipita-FECYT crowdfunding program [PR194]; Gobierno de Aragón [LMP135_18, Grupos Consolidados B33_17R] and FEDER 2014–2020 “Construyendo Europa desde Aragón”. CIBERER is an initiative of the ISCIII

Characterization of the electrocardiographic pattern of individuals with cerebral palsy

Background: Dentists of Lar Sao Francisco observed during dental treatment that children with cerebral palsy (CP) had increased heart rate (HR) and lower production of saliva. Despite the high prevalence of CP found in the literature (2.08-3.6/1000 individuals), little is known about the electrocardiographic (ECG) characteristics, especially HR, of individuals with CP. Objective: This study aimed to investigate the hypothesis that individuals with CP have a higher HR and to define other ECG characteristics of this population. Methods: Ninety children with CP underwent clinical examination and 12-lead rest ECG. Electrocardiographic data on rhythm, HR, PR interval, QRS duration, P/QRS/T axis, and QT, QTc and T(peak-end) intervals (minimum, mean, maximum, and dispersion) were measured and analyzed then compared with data from a control group with 35 normal children. Fisher and Mann-Whitney U tests were used, respectively, to compare categorical and continuous data. Results: Groups cerebral palsy and control did not significantly differ in age (9 +/- 3 x 9 +/- 4 years) and male gender (65% x 49%). Children with CP had a higher HR (104.0 +/- 20.6 x 84.2 +/- 13.3 beats per minute; P < .0001), shorter PR interval (128.8 +/- 15.0 x 138.1 +/- 15.1 milliseconds; P = .0018), shorter QRS duration (77.4 +/- 8.6 x 82.0 +/- 8.7 milliseconds; P = .0180), QRS axis (46.0 degrees +/- 26.3 degrees x 59.7 degrees +/- 24.8 degrees; P = .0024) and T-wave axis (34.3 degrees +/- 28.9 degrees x 42.9 degrees +/- 17.1 degrees; P = .034) more horizontally positioned, and greater mean QTc (418.1 +/- 18.4 x 408.5 +/- 19.4 milliseconds; P = .0110). All the electrocardiogram variables were within the reference range for the age group including those with significant differences. Conclusion: Children with CP showed increased HR and other abnormal ECG findings in the setting of this investigation. Further studies are needed to explain our findings and to correlate the increased HR with situations such as dehydration, stress, and autonomic nervous disorders. (C) 2011 Elsevier Inc. All rights reserved

Avaliação do efeito do extrato hidroalcoólico de Schinus terebinthifolius Raddi (Aroeira) no processo de cicatrização da linea alba de ratos Evaluation of the hydro-alcoholic Schinus terebinthifolius Raddi (Aroeira) extract in the healing process of the alba linea in rats

OBJETIVO: Avaliar o processo de cicatrização da parede abdominal de ratos após a injeção intraperitoneal do extrato hidroalcóolico de Schinus terebinthifolius Raddi. MÉTODOS: Utilizaram-se 40 ratos da linhagem Wistar, distribuídos em dois grupos de 20 animais, cada um subdividido em dois subgrupos. Estes ratos foram mortos no 3º e 7º dias após a aplicação intraperitoneal do extrato. No grupo experimento, injetou-se uma única dose de extrato hidroalcoólico de Aroeira (100 mg por quilo de peso do animal) e no grupo controle uma única dose de solução salina isotônica a 0.9%. Após a morte dos animais, realizou-se o inventário da cavidade peritoneal à procura de aderências, seguido da ressecção da parede abdominal anterior englobando a ferida operatória para análise. As aderências foram classificadas pelos critérios de adesão de Nair. Realizou-se avaliação tensiométrica da parede abdominal através da medida da carga máxima suportada e da deformação máxima, medidos em máquina universal de ensaios do tipo Tiratest. Por fim, a avaliação histológica foi realizada através da coloração hematoxilina-eosina, com análise dos parâmetros: inflamação aguda, inflamação crônica, necrose isquêmica, reação gigantocelular do tipo corpo estranho, proliferação fibroblástica, fibrose, reepitelização e coaptação das bordas da sutura. RESULTADOS: A avaliacão macroscópica não revelou presença de aderências significativas entre a linha alba e as vísceras intra-abdominais nos grupos de estudo. A tensiometria demonstrou aumento significativo das variáveis carga máxima e deformação máxima (p=0,006 e p=0,000 respectivamente) entre os grupos controle e experimento de sete dias. A avaliação histológica intergrupos (controle e experimento) de três e sete dias não demonstrou alteração significativa para os parâmetros neoformação vascular, necrose, fibrose, reepitelização e coaptação das bordas da sutura. Notou-se diferença significativa para proliferação fibroblástica (p=0,014) na avaliação intergrupo de três dias, e para inflamação crônica (p=0,023) e reação gigantocelular do tipo corpo estranho (p=0,008) na avaliação intergrupo de sete dias. Na análise intragrupo controle, houve diferença significativa para inflamação crônica no subgrupo três dias, e, finalmente, na análise intragrupo experimento, observou-se diferença significativa para inflamação aguda e proliferação de fibroblastos (p=0,001 e p=0,020) no subgrupo de três dias em relação ao subgrupo de sete. CONCLUSÃO: A injeção intraperitoneal do extrato hidroalcoólico de Schinus terebinthifolius Raddi em laparotomias medianas de ratos não alterou a cicatrização na análise macroscópica e induziu a aumento da carga máxima de ruptura e deformação máxima da linha alba na análise tensiométrica. Na análise histológica, determinou efeito cicatrizante no subgrupo de animais experimento de três dias.<br>PURPOSE: To evaluate the healing process in the abdominal wall of rats after the intra-peritoneal injection of the hydro-alcoholic Schinus terebinthifolius Raddi extract. METHODS: Forty Wistar rats were used, distributed in two groups of 20 animals, divided into two subgroups, according to the death day, three or seven, after the intra-peritoneal injection of the extract. The experimental group was injected with only one dose of the hydro-alcoholic Aroeira extract (100mg per animal kilogram); the control group was injected with only one dose of isotonic saline solution at 0.9%. After the animal death, an inventory of the peritoneal cavity was carried out in a careful search for any adhesion, followed by the resection of the anterior abdominal wall encompassing the operating incision in order to examine it for evidence of infection. The adhesions were classified according to the Nair criteria. The tensiometric assessment was performed by means of the measurement of the maximum charge and maximum deformity tolerated, measured in a universal Tiratest type testing machine and, finally, the histological evaluation was performed by means of the hematoxylin-eosine staining in following parameters: severe inflammation, chronic inflammation, ischemic necrosis, gigantocellular reaction of the foreign body type, fibroblastic proliferation, fibrosis, re-epithelization and co-optation of the suture borders. RESULTS: The macroscopic evaluation didn't have any evidence of significant adherence between the alba linea and the intra-abdominal viscera in the study groups. The tensiometry showed significant effect for the Maximum Charge and Maximum Deformity (p=0.006 and p=0.000, respectively) between the 7-day control and experimental groups. The histological 3-day and 7-day control and experimental intergroup evaluation did not show significant alteration for the parameters vascular neoformation, necrosis, fibrosis, re-epithelization and co-aptation. A significant difference was perceived for fibroblastic proliferation (p=0.014) in the 3-day intergroup evaluation and for chronic inflammation (p=0.023) and gigantocellular reaction of the foreign body type (p=0.008) in the 7-day intergroup evaluation. The control intragroup analysis, had a significant difference for chronic inflammation in the 3-day group and, finally, in the experimental intragroup analysis, a significant difference was observed for acute inflammation and fibroblastic proliferation (p=0.001 and p=0.020) in the 3-day regarding the 7-day group. CONCLUSION: The intraperitoneal injection of the Schinus terebinthifolius Raddi hydro-alcoholic extract in median laparotomies in rats has not determined any significant alteration in the macroscopic analysis, but it induced an increase of maximum charge of rupture and maximum deformity of the alba linea in the tensiometric analysis. In the histological point of view, the Aroeira group had a positive healing effect on the 3-day