149 research outputs found
Polycomb group ring finger protein 6 suppresses Myc-induced lymphomagenesis
No full textMax is an obligate dimerization partner for the Myc transcription factors and for several repressors, such as Mnt, Mxd1-4, and Mga, collectively thought to antagonize Myc function in transcription and oncogenesis. Mga, in particular, is part of the variant Polycomb group repressive complex PRC1.6. Here, we show that ablation of the distinct PRC1.6 subunit Pcgf6-but not Mga- accelerates Myc-induced lymphomagenesis in Eμ-myc transgenic mice. Unexpectedly, however, Pcgf6 loss shows no significant impact on transcriptional profiles, in neither pre-tumoral B-cells, nor lymphomas. Altogether, these data unravel an unforeseen, Mga- and PRC1.6-independent tumor suppressor activity of Pcgf6
The good Pope : British reactions to the Papacy of Pius IX, 1846-52
No full textFrom the time of the Reformation in England Anglo-vatican
relations have typically been seen as a long history of
unending antagonism. It is not common knowledge that in
the period between 1846 and 1851 there was a notable, if
temporary, lull in this animosity and even talk of
establishing full diplomatic relations. This thesis aims
to account for this thaw in tensions and to analyse the
British response to the early 'liberal' years of Pope
Pius IX, not only looking at government policy but also
the attitude of the British public towards the new Pope.
In addition, this study sets out not only to look at
individual issues, such as the Risorgimento, the history
of the Roman Catholic Church in England and the Irish
question, but seeks to explain the interplay between them
in order to come to a fuller understanding of British
policy.
This thesis reveals that British policy was based on the
need to achieve a number of goals, such as a peaceful
solution to the political crisis in the Italian peninsula
and the curbing of the Irish agitation, and that it was
held that an enlightened Pope could help in the
fulfilment of these aims. The effort to improve relations
in the end failed as it was undermined by an overoptimistic
assessment of the Pope's liberalism and
failure of the British government to appreciate the depth
of anti-Catholic opinion among the British public and
their representatives in Parliament. The result was that
this short thaw in relations came to an abrupt end
Integrated requirement of non-specific and sequence-specific DNA binding in Myc-driven transcription
No full textEukaryotic transcription factors recognize specific DNA sequence motifs, but are also endowed with generic, non-specific DNA-binding activity. How these binding modes are integrated to determine select transcriptional outputs remains unresolved. We addressed this question by site-directed mutagenesis of the Myc transcription factor. Impairment of non-specific DNA backbone contacts caused pervasive loss of genome interactions and gene regulation, associated with increased intra-nuclear mobility of the Myc protein in murine cells. In contrast, a mutant lacking base-specific contacts retained DNA-binding and mobility profiles comparable to those of the wild-type protein, but failed to recognize its consensus binding motif (E-box) and could not activate Myc-target genes. Incidentally, this mutant gained weak affinity for an alternative motif, driving aberrant activation of different genes. Altogether, our data show that non-specific DNA binding is required to engage onto genomic regulatory regions; sequence recognition in turn contributes to transcriptional activation, acting at distinct levels: stabilization and positioning of Myc onto DNA, and—unexpectedly—promotion of its transcriptional activity. Hence, seemingly pervasive genome interaction profiles, as detected by ChIP-seq, actually encompass diverse DNA-binding modalities, driving defined, sequence-dependent transcriptional responses
Pedaleando memoria
No full textDesde 2014 UADER desarrolla la Agenda M (Mujer, Memoria, Malvinas), buscando entrelazar el sentido de estas tres conmemoraciones con impronta en los derechos humanos, convocando a la comunidad universitaria a debatir y reflexionar sobre esas fechas.
En marzo de 2021 empezamos a preguntarnos en Facultad de Ciencia y Tecnología, qué hacer para recordar el 24 de marzo, pues seguíamos en pandemia. Así comienza esta idea de recorrer lugares de Memoria, en bicicleta, pues era lo posible, una forma de poder juntarnos, al aire libre, en un escenario todavía de aulas virtuales, barbijos, saludos con el puño.
Desde esta realidad de pandemia y este marco teórico fue pensada “Pedaleando Memoria” que se concretó en 2022, como una actividad social de sensibilización que se propone realizar un recorrido grupal en bicicleta por algunos de los ex centros clandestinos de detención que funcionaron en la ciudad de Paraná, donde se produjeron violaciones sistemáticas de los derechos humanos.
El propósito es construir colectivamente una jornada de reflexión, a través del movimiento y la circulación por las calles, haciendo paradas en estos sitios de memoria para “reactualizar” el sentido de la marca territorial resignificándola, favoreciendo el ejercicio de la memoria colectiva.Universidad Nacional de La Plat
Cooperation between MYC and β-catenin in liver tumorigenesis requires Yap/Taz
No full textActivation of MYC and CTNNB1 (encoding β-catenin) can co-occur in liver cancer, but how these oncogenes cooperate in tumorigenesis remains unclear. Approach & Results We generated a mouse model allowing conditional activation of MYC and WNT/β-catenin signaling (through either β-catenin activation or Apc loss) upon expression of CRE recombinase in the liver, and monitored their effects on hepatocyte proliferation, apoptosis, gene expression profiles and tumorigenesis. Activation of WNT/β-catenin signaling strongly accelerated MYC-driven carcinogenesis in the liver. Both pathways also cooperated in promoting cellular transformation in vitro, demonstrating their cell-autonomous action. Short-term induction of MYC and β-catenin in hepatocytes followed by RNA-seq profiling allowed the identification of a "Myc/β-catenin signature", composed of a discrete set of Myc-activated genes whose expression increased in the presence of active β-catenin. Notably this signature enriched for targets of Yap and Taz, two transcriptional co-activators known to be activated by WNT/β-catenin signaling, and to cooperate with MYC in mitogenic activation and liver transformation. Consistent with these regulatory connections, Yap/Taz accumulated upon Myc/β-catenin activation and were required not only for the ensuing proliferative response, but also for tumor cell growth and survival. Finally, the Myc/β-catenin signature was enriched in a subset of human hepatocellular carcinomas characterized by comparatively poor prognosis
Search for excited electrons and muons in √s=8 TeV proton–proton collisions with the ATLAS detector
No full textThe ATLAS detector at the Large Hadron Collider is used to search for excited electrons and excited muons in the channel pp → ℓℓ* → ℓℓγ, assuming that excited leptons are produced via contact interactions. The analysis is based on 13 fb[superscript −1] of pp collisions at a centre-of-mass energy of 8 TeV. No evidence for excited leptons is found, and a limit is set at the 95% credibility level on the cross section times branching ratio as a function of the excited-lepton mass m[subscript ℓ*]. For m[subscript ℓ*] ≥ 0.8 TeV, the respective upper limits on σB(ℓ* → ℓγ) are 0.75 and 0.90 fb for the e* and μ* searches. Limits on σB are converted into lower bounds on the compositeness scale Λ. In the special case where Λ = m[subscript ℓ*], excited-electron and excited-muon masses below 2.2 TeV are excluded.United States. Dept. of EnergyNational Science Foundation (U.S.)Brookhaven National Laborator
SU‐E‐T‐299: Small Fields Profiles Correction Through Detectors Spatial Response Functions and Field Size Dependence Analysis
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