Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Nutzung und Qualität von Tagesschulen und Schülerclubs in der Stadt Zürich : erste Ergebnisse aus einer Elternbefragung

TesisLa Ley General de Sociedades plantea cinco formas societarias, dentro de las cuales tenemos a las sociedades anónimas, sociedades colectivas, sociedad comandita, sociedad comercial de responsabilidad limitada y por último las sociedades civiles. Todas ellas están reguladas en el Libro III de la Ley General de Sociedades Nº26887. Pero, no se debe dejar de lado que el derecho es una disciplina cambiante y la cual se adecua al paso del tiempo; razón por la cual nadie podría negar que algunas de las formas societarias propuestas por la ley, en la actualidad se encuentran en desuso. En el presente trabajo expondremos las desventajas de constituir sociedades como la sociedad colectiva, sociedad comandita y sociedad civiles, las cuales en la práctica ya no son competentes; lo que nos lleva a la necesidad de una modificación de la Ley General de Sociedades; todo ello con el fin que las nuevas empresas nazcan con un mayor poder competitivo en el ámbito empresarial. Razón por la cual, se abordará el tema de la falta de utilidad y competitividad en la realidad actual de la sociedad colectiva, comandita y sociedades civiles, ya que como se demostrará a continuación al compararlas con las sociedades anónimas y de responsabilidad limitada, estas últimas ofrecen al público diversas ventajas que no se obtendrían al conformar una sociedad colectiva, comandita o civil. Tal comparación ha sido la raíz para que, en la actualidad no se conformen muchas sociedades bajo estas tres modalidades, a comparación de la cantidad de sociedades anónimas y de responsabilidad limitada que en la actualidad están inscritas en Registros Públicos y las que cada día se conforman en las diferentes Notarias. Por lo que, con el fin de probar lo aseverado en el párrafo anterior, se ha utilizado la técnica de observación documental, mediante la cual se han consultado tanto en las Notarías Publicas de la provincia de Arequipa como en la Zona Registral N°XII – Sede Arequipa, la cantidad de escrituras públicas realizadas en las notarías y la cantidad de escrituras públicas que se han llegado a inscribir en SUNARP. Téngase presente que se está reclutando datos de dos fuentes muy importantes, la primera la Superintendencia Nacional de Registros Públicos, la cual no solo ha proporcionado datos de los años 2014 y 2015 sino, nos ha proporcionado la cantidad de sociedades civiles, comanditas y colectivas inscritas en total, desde que se constituyó el sistema informático de SUNARP. La segunda fuente está dirigida más a la cantidad de Escrituras Públicas de constitución de estos tipos societarios, realizadas en los años 2014 y 2015 en las diferentes notarias de Arequipa, proporcionándonos el dato si en los últimos años aún siguen vigentes o no. Resultados que han demostrado que la hipótesis planteada es correcta; debido a que sí es necesario un cambio en la normatividad en materia societaria, debido a la pérdida de vigencia de las sociedades colectiva, sociedad en comandita y sociedades civiles a razón de su falta de utilidad y competitividad en la realidad actual, tal como se ha demostrado tanto doctrinariamente como en la investigación realizada en campo. Palabras clave: Sociedad civi, colectiva, comandita

Musikalische Bildung im Kontext der Ganztagsbildung

Musisch-kulturelle Bildung als Element der Ganztagsbildung ist nebst dem meist vorhandenen extracurricularen Sportprogramm laut Elternbefragung in Zürich, Schweiz, erwünscht und aus wissenschaftlicher Perspektive wirkungsvoll in Bezug auf das Sozialverhalten der Kinder in der Klasse und die Aspekte der Chancengleichheit und der Teilhabe an Bildung. Bestehende nationale Projekte werden kurz beschrieben und konkrete Angebote zu einer möglichen Profilbildung von Schulen mit musisch-kulturellem Fokus werden skizziert. Die zu erwartenden Konsequenzen auf den Ebenen der Schulqualität und der Akteure werden abschliessend formuliert.According to the opinion of parents from the City of Zurich music and cultural education is lacking in the curriculum of extended education. In contrast, education in sports is well established. In previous German studies investigating music education a positive effect in terms of children’s social behaviour in the classroom and aspects of equality in education was demonstrated. In the present article we describe music education programs and possible additional extracurricular activities aiming to strengthen individual school’s music and cultural profiles. Expected consequences on the school quality level are considered

Role of the Cardiophrenic Lymph Node Status After Neoadjuvant Chemotherapy in Primary Advanced Ovarian Cancer

Background/Aim: This study investigated the cardiophrenic lymph node (CPLN) status before and after neoadjuvant chemotherapy (NACT), as its presence seems to have a rather prognostic significance in patients with advanced ovarian cancer. Patients and Methods: The baseline computed tomography scans of 66 patients with advanced ovarian cancer primary treated with NACT between March 2015 and June 2020 were reviewed. A CPLN enlargement was defined as =5 mm. Results: 44% (n=29) of the patients had enlarged CPLNs; 10.7% (n=3) showed a complete response, 71.4% (n=20) a partial response, and 17.9% ( n=5) a stable disease after NACT. There was no significant difference between the response to NACT measured according to the status of CPLN compared to other biomarkers in the CPLN group. Conclusion: Patients with CPLN enlargement have a tendency to an impaired prognosis. The response of CPLN to NACT was comparable to the response of established biomarkers, adding a monitoring function to the CPLN

The human cytomegalovirus protein UL147A downregulates the most prevalent MICA allele: MICA*008, to evade NK cell-mediated killing.

Natural killer (NK) cells are innate immune lymphocytes capable of killing target cells without prior sensitization. One pivotal activating NK receptor is NKG2D, which binds a family of eight ligands, including the major histocompatibility complex (MHC) class I-related chain A (MICA). Human cytomegalovirus (HCMV) is a ubiquitous betaherpesvirus causing morbidity and mortality in immunosuppressed patients and congenitally infected infants. HCMV encodes multiple antagonists of NK cell activation, including many mechanisms targeting MICA. However, only one of these mechanisms, the HCMV protein US9, counters the most prevalent MICA allele, MICA*008. Here, we discover that a hitherto uncharacterized HCMV protein, UL147A, specifically downregulates MICA*008. UL147A primarily induces MICA*008 maturation arrest, and additionally targets it to proteasomal degradation, acting additively with US9 during HCMV infection. Thus, UL147A hinders NKG2D-mediated elimination of HCMV-infected cells by NK cells. Mechanistic analyses disclose that the non-canonical GPI anchoring pathway of immature MICA*008 constitutes the determinant of UL147A specificity for this MICA allele. These findings advance our understanding of the complex and rapidly evolving HCMV immune evasion mechanisms, which may facilitate the development of antiviral drugs and vaccines

Clinical and Cytogenetic Characterization of Early and Late Relapses in Patients Allografted for Myeloid Neoplasms with a Myelodysplastic Component

An improved understanding of relapse kinetics is required to optimize detection and treatment strategies for the post-transplant relapse of myeloid neoplasms. Therefore, we retrospectively analyzed data from 91 patients allografted for MDS (n = 54), AML-MRC (n = 29) and chronic myelomonocytic leukemia (CMML, n = 8), who relapsed after transplant. Patients with early (n = 56) and late relapse (>12 months, n = 35) were compared regarding patient-, disease- and transplant-related factors, including karyotype analyses at diagnosis and relapse. After a median follow-up of 17.4 months after relapse, late relapses showed improved outcomes compared with early relapses (2-yr OS 67% vs. 32%, p = 0.0048). Comparing frequency of distinct patient-, disease- and transplant-related factors among early and late relapses, complex karyotype (p = 0.0004) and unfavorable disease risk at diagnosis (p = 0.0008) as well as clonal evolution at relapse (p = 0.03) were more common in early than in late relapses. Furthermore, patients receiving transplant without prior cytoreduction or in complete remission were more frequently present in the group of late relapses. These data suggest that cytogenetics rather than disease burden at diagnosis and transplant-related factors determine the timepoint of post-transplant relapse and that upfront transplantation may be favored in order to delay relapse

The importance of the Peritoneal Cancer Index (PCI) to predict surgical outcome after neoadjuvant chemotherapy in advanced ovarian cancer

Purpose Achieving complete cytoreduction (CCR) is crucial for a patient's prognosis with advanced epithelial ovarian cancer (EOC). So far, prognostic predictors have failed to predict surgical outcome after neoadjuvant chemotherapy (NACT). In clinical trials, scores were used to predict operability in recurrent ovarian cancer (Harter et al. in N Engl J Med 385(23):2123-2131, 2021) but there is no known prediction score for CCR after NACT. The Peritoneal Cancer Index (PCI) is an established tool to predict surgical outcome in primary setting (Lampe et al. in 25:135-144, 2015). We now examined the predictive power of the PCI to achieve CCR after NACT. Methods In this single-center study, the data of patients with advanced stage EOC (FIGO > IIIb) treated between 01/2015 and 12/2020 were analyzed retrospectively. Inclusion criteria were a mandatory staging laparoscopy, a PCI score > 25, and NACT. CT scans were analyzed in blinded fashion according to RECIST criteria (Borgani et al. in 237; 93-99, 2019) Reaction of PCI after NACT was compared with the analysis of radiologic imaging and CA-125 levels. Results Three hundred and sixteen patients were screened, 62 were treated with NACT, and 23 were included in our analysis. 87% of cases presented with an FIGO IIIc stadium. The reduction of PCI itself after NACT showed to be the most powerful predictor for achieving CCR. The reduction of the initial PCI score by minimum of 8.5 points was a better predictor for CCR than reaching a PCI < 25. In contrast to data deriving from patients undergoing primary debulking surgery (PDS), we found a PCI of 17, rather than 25, to be a more valuable cut-off for CCR in neoadjuvant-treated patients. Conclusion The extend of PCI reduction after NACT is a better predictor for achieving CCR compared with CA125 levels and radiologic imaging. The PCI must be assessed differently in neoadjuvant setting than in a primary situation. CCR was most likely for a post-NACT PCI < 17