On the relation between boundary proposals and hidden symmetries of the extended pre-big bang quantum cosmology

A framework associating quantum cosmological boundary conditions to minisuperspace hidden symmetries has been introduced in \cite{7}. The scope of the application was, notwithstanding the novelty, restrictive because it lacked a discussion involving realistic matter fields. Therefore, in the herein letter, we extend the framework scope to encompass elements from a scalar-tensor theory in the presence of a cosmological constant. More precisely, it is shown that hidden minisuperspace symmetries present in a pre-big bang model suggest a process from which boundary conditions can be selected.Comment: 15 pages, no figures, to appear in European Physical Journal

PITX1, a specificity determinant in the HIF-1α-mediated transcriptional response to hypoxia

Hypoxia is an important developmental cue for multicellular organisms but it is also a contributing factor for several human pathologies, such as stroke, cardiovascular diseases and cancer. In cells, hypoxia activates a major transcriptional program coordinated by the Hypoxia Inducible Factor (HIF) family. HIF can activate more than one hundred targets but not all of them are activated at the same time, and there is considerable cell type variability. In this report we identified the paired-like homeodomain pituitary transcription factor (PITX1), as a transcription factor that helps promote specificity in HIF-1α dependent target gene activation. Mechanistically, PITX1 associates with HIF-1β and it is important for the induction of certain HIF-1 dependent genes but not all. In particular, PITX1 controls the HIF-1α-dependent expression of the histone demethylases; JMJD2B, JMJD2A, JMJD2C and JMJD1B. Functionally, PITX1 is required for the survival and proliferation responses in hypoxia, as PITX1 depleted cells have higher levels of apoptotic markers and reduced proliferation. Overall, our study identified PITX1 as a key specificity factor in HIF-1α dependent responses, suggesting PITX1 as a protein to target in hypoxic cancers