Differentiation-Defective Human Induced Pluripotent Stem Cells Reveal Strengths and Limitations of the Teratoma Assay and In Vitro Pluripotency Assays

Stem cells & developmental biolog

Gender and outcome in adult congenital heart disease.

Contains fulltext : 70221.pdf (publisher's version ) (Open Access)BACKGROUND: Gender differences in prognosis have frequently been reported in cardiovascular disease but less so in congenital heart disease. We investigated whether gender is associated with outcome in adult patients with congenital heart disease. METHODS AND RESULTS: From the CONgenital CORvitia (CONCOR) national registry for adults with congenital heart disease, 7414 patients were identified. All outcomes before entry into the registry and during subsequent follow-up were recorded, and differences between men and women were analyzed with the underlying congenital heart defect taken into account. Median age at the end of follow-up was 35 years (range, 17 to 91 years); 49.8% were female. No gender difference in mortality was found. Women had a 33% higher risk of pulmonary hypertension (odds ratio [OR]=1.33; 95% CI, 1.07 to 1.65; P=0.01), a 33% lower risk of aortic outcomes (OR=0.67; 95% CI, 0.50 to 0.90; P=0.007), a 47% lower risk of endocarditis (OR=0.53; 95% CI, 0.40 to 0.70; P<0.001), and a 55% lower risk of an implantable cardioverter-defibrillator (OR=0.45; 95% CI, 0.26 to 0.80; P=0.006). Furthermore, the risk of arrhythmias appeared to be lower in women (OR=0.88; 95% CI, 0.77 to 1.02; P=0.08). CONCLUSIONS: The risk of several major cardiac outcomes in adult patients with congenital heart disease appears to vary by gender

Generation and genetic repair of 2 iPSC clones from a patient bearing a heterozygous c.1120del18 mutation in the ACVRL1 gene leading to Hereditary Hemorrhagic Telangiectasia (HHT) type 2

Fibroblasts from a patient carrying a heterozygous 18bp deletion in exon 8 of the ACVRL1 gene (c.1120del18) were reprogrammed using episomal vectors. The inframe deletion in ACVRL1 causes the loss of 6 amino acids of the protein, which is associated with Hereditary Hemorrhagic Telangiectasia (HHT) type 2 ). (Letteboer et al., 2005). CRISPR-Cas9 editing was used to genetically correct the mutation in the induced pluripotent stem cells (iPSCs). The top5-predicted off-target sites were not altered. Patient and isogenic iPSCs showed high pluripotent marker expression, in vitro differentiation capacity into all three germ layers and displayed a normal karyotype. The obtained isogenic pairs will enable proper in vitro disease modelling of HHT (Roman and Hinck, 2017)

Mapping of Apoptin interaction with BCR-ABL1, and development of apoptin-based targeted therapy

Majority of chronic myeloid leukemia patients experience an adequate therapeutic effect from imatinib however, 26-37% of patients discontinue imatinib therapy due to a suboptimal response or intolerance. Here we investigated derivatives of apoptin, a chicken anemia viral protein with selective toxicity towards cancer cells, which can be directed towards inhibiting multiple hyperactive kinases including BCR-ABL1. Our earlier studies revealed that a proline-rich segment of apoptin interacts with the SH3 domain of fusion protein BCR-ABL1 (p210) and acts as a negative regulator of BCR-ABL1 kinase and its downstream targets. In this study we show for the first time, the therapeutic potential of apoptin-derived decapeptide for the treatment of CML by establishing the minimal region of apoptin interaction domain with BCR-ABL1. We further show that the apoptin decapeptide is able to inhibit BCR-ABL1 down stream target c-Myc with a comparable efficacy to full-length apoptin and Imatinib. The synthetic apoptin is able to inhibit cell proliferation in murine (32Dp210), human cell line (K562), and ex vivo in both imatinib-resistant and imatinib sensitive CML patient samples. The apoptin based single or combination therapy may be an additional option in CML treatment and eventually be feasible as curative therapy

Genetic diversity of oral Fusobacterium nucleatum isolated from patients with different clinical conditions Diversidade genética de Fusobacterium nucleatum orais isolados de pacientes com diferentes condições clínicas

The genetic diversity of 23 oral Fusobacterium nucleatum isolated from 15 periodontal patients, eight from seven healthy subjects, nine from nine AIDS patients and two from two Cebus apella monkeys were analyzed. EcoRI restricted the bacterial DNA and 28 ribotypes grouped from A to J groups were obtained. Isolates formed 24 ribotypes which were contained into A, B, C, D, E and F groups, and three reference strains and two clinical isolates of A. actinomycetemcomitans, and E. coli CDC formed four different ribotypes into the G, H, I and J groups. Moreover, from nine F. nucleatum from AIDS patients, six were ribotyped as group C and three as group D. By using ribotyping we distinguished F. nucleatum recovered from different sources. It is possible that isolates from AIDS patients may contain some phenotypic or genotypic factor did not observed in this study.<br>Neste estudo foi avaliada a diversidade genética de 23 amostras de Fusobacterium nucleatum isoladas da cavidade bucal de 15 pacientes com doença periodontal, de oito cepas isoladas de sete indivíduos sadios, de nove isoladas de nove pacientes com AIDS e de duas isoladas de dois macacos Cebus apella. Pela ação da enzima EcoRI sobre o DNA bacteriano foram reconhecidos 28 ribotipos agrupados de A a J. Os isolados testados formaram 24 ribotipos os quais foram contidos nos grupos A, B, C, D, E e F, e as três cepas de referência e dois isolados clínicos de A. actinomycetemcomitans e E. coli CDC formaram quatro diferentes ribotipos contidos nos grupos G, H, I e J. Em adição, as nove cepas de F. nucleatum isoladas de pacientes com AIDS, seis pertenciam ao grupo C e três ao grupo D. Usando-se a ribotipagem foi possível distinguir F. nucleatum isolados de diferentes origens