The Dynamical State fo the Starless Dense Core FeSt 1-457: A Pulsating Globule?

High resolution molecular line observations of CS, HCO+, C18O and N2H+ were obtained toward the starless globule FeSt 1-457 in order to investigate its kinematics and chemistry. The HCO+ and CS spectra show clear self-reversed and asymmetric profiles across the face of the globule. The sense of the observed asymmetry is indicative of the global presence of expansion motions in the outer layers of the globule. These motions appear to be subsonic and significantly below the escape velocity of the globule. Comparison of our observations with near-infrared extinction data indicate that the globule is gravitationally bound. Taken together these considerations lead us to suggest that the observed expansion has its origin in an oscillatory motion of the outer layers of the globule which itself is likely in a quasi-stable state near hydrostatic equilibrium. Analysis of the observed linewidths of CO and N2H+ confirm that thermal pressure is the dominant component of the cloud's internal support. A simple calculation suggests that the dominant mode of pulsation would be an l = 2 mode with a period of 0.3 Myr. Deformation of the globule due to the large amplitude l = 2 oscillation may be responsible for the double-peaked structure of the core detected in high resolution extinction maps. Detailed comparison of the molecular-line observations and extinction data provides evidence for significant depletion of C18O and perhaps HCO+ while N2H+ may be undepleted to a cloud depth of about 40 magnitudes of visual extinction.Comment: to appear in ApJ vol 665 20 August 2007

I conflitti religiosi nella scena pubblica. Vol. 2: Pace nella \uabCivitas\ubb

Il volume \ue8 in continuit\ue0 con un volume precedente (I conflitti religiosi nella scena pubblica. I. Agostino a confronto con manichei e donatisti, a cura di L. Alici, Citt\ue0 Nuova, Roma 2015). Tema centrale \ue8 la vocazione universale del cristianesimo, che in Agostino assume il carattere di un riconoscimento sempre pi\uf9 esplicito e articolato, fino a trasformarsi, in particolare nel De civitate Dei, in uno sguardo capace di proiettare l\u2019annuncio evangelico non solo oltre le barriere dello spazio, che delimitavano i confini delle razze, delle lingue e delle culture, facendole coincidere anche con i particolarismi dei culti religiosi, ma addirittura oltre le barriere del tempo; al punto tale, che il cristiano riesce a scorgere nella crisi della forma politica romana solo la fine di un epoca, e non certo la fine della storia. I saggi che compongono il volume esplorano la questione da due diverse angolature, in qualche modo complementari: nella prima parte, la conflittualit\ue0 viene riportata all\u2019interno del confronto tra politeismo e monoteismo; nella seconda, viene tematizzata la risposta di Agostino, incentrata sul ripensamento della nozione di civitas nella prospettiva della pac

A recurrent COL6A1 pseudoexon insertion causes muscular dystrophy and is effectively targeted by splice-correction therapies

The clinical application of advanced next-generation sequencing technologies is increasingly uncovering novel classes of mutations that may serve as potential targets for precision medicine therapeutics. Here, we show that a deep intronic splice defect in the COL6A1 gene, originally discovered by applying muscle RNA sequencing in patients with clinical findings of collagen VI–related dystrophy (COL6-RD), inserts an in-frame pseudoexon into COL6A1 mRNA, encodes a mutant collagen α1(VI) protein that exerts a dominant-negative effect on collagen VI matrix assembly, and provides a unique opportunity for splice-correction approaches aimed at restoring normal gene expression. Using splice-modulating antisense oligomers, we efficiently skipped the pseudoexon in patient-derived fibroblast cultures and restored a wild-type matrix. Similarly, we used CRISPR/Cas9 to precisely delete an intronic sequence containing the pseudoexon and efficiently abolish its inclusion while preserving wild-type splicing. Considering that this splice defect is emerging as one of the single most frequent mutations in COL6-RD, the design of specific and effective splice-correction therapies offers a promising path for clinical translation