H2_2 ortho-to-para conversion on grains: A route to fast deuterium fractionation in dense cloud cores?

Deuterium fractionation, i.e. the enhancement of deuterated species with respect to the non-deuterated ones, is considered to be a reliable chemical clock of star-forming regions. This process is strongly affected by the ortho-to-para (o-p) H$_2$ ratio. In this letter we explore the effect of the o-p H$_2$ conversion on grains on the deuteration timescale in fully depleted dense cores, including the most relevant uncertainties that affect this complex process. We show that (i) the o-p H$_2$ conversion on grains is not strongly influenced by the uncertainties on the conversion time and the sticking coefficient and (ii) that the process is controlled by the temperature and the residence time of ortho-H$_2$ on the surface, i.e. by the binding energy. We find that for binding energies in between 330-550 K, depending on the temperature, the o-p H$_2$ conversion on grains can shorten the deuterium fractionation timescale by orders of magnitude, opening a new route to explain the large observed deuteration fraction $D_\mathrm{frac}$ in dense molecular cloud cores. Our results suggest that the star formation timescale, when estimated through the timescale to reach the observed deuteration fractions, might be shorter than previously proposed. However, more accurate measurements of the binding energy are needed to better assess the overall role of this process.Comment: Accepted for publication in ApJ Letter

A complex of α6 integrin and E-cadherin drives the liver metastasis of colorectal cancer cells by a physical and functional interaction with hepatic angiopoietin-like 6

Homing of colorectal cancer (CRC) cells to the liver is a non-random process driven by a crosstalk between tumour cells and components of the host tissue. Here we report the isolation of a liver metastasis-specific peptide ligand (CGIYRLRSC) that binds a complex of E-cadherin and α(6) integrin on the surface of CRC cells. We identify angiopoietin-like 6 protein as a peptide-mimicked natural ligand enriched in hepatic blood vessels of CRC patients. We demonstrate that an interaction between hepatic angiopoietin-like 6 and tumoural α(6) integrin/E-cadherin drives liver homing and colonization by CRC cells, and that CGIYRLRSC inhibits liver metastasis through interference with this ligand/receptor system. Our results indicate a mechanism for metastasis whereby a soluble factor accumulated in normal vessels functions as a specific ligand for circulating cancer cells. Consistently, we show that high amounts of coexpressed α(6) integrin and E-cadherin in primary tumours represent a poor prognostic factor for patients with advanced CRC

The CD157-Integrin Partnership Controls Transendothelial Migration and Adhesion of Human Monocytes*

CD157, a member of the CD38 gene family, is an NAD-metabolizing ectoenzyme and a signaling molecule whose role in polarization, migration, and diapedesis of human granulocytes has been documented; however, the molecular events underpinning this role remain to be elucidated. This study focused on the role exerted by CD157 in monocyte migration across the endothelial lining and adhesion to extracellular matrix proteins. The results demonstrated that anti-CD157 antibodies block monocyte transmigration and adhesion to fibronectin and fibrinogen but that CD157 cross-linking is sufficient to overcome the block, suggesting an active signaling role for the molecule. Consistent with this is the observation that CD157 is prevalently located within the detergent-resistant membrane microdomains to which, upon clustering, it promotes the recruitment of β1 and β2 integrin, which, in turn, leads to the formation of a multimolecular complex favoring signal transduction. This functional cross-talk with integrins allows CD157 to act as a receptor despite its intrinsic structural inability to do so on its own. Intracellular signals mediated by CD157 rely on the integrin/Src/FAK (focal adhesion kinase) pathway, resulting in increased activity of the MAPK/ERK1/2 and the PI3K/Akt downstream signaling pathways, which are crucial in the control of monocyte transendothelial migration. Collectively, these findings indicate that CD157 acts as a molecular organizer of signaling-competent membrane microdomains and that it forms part of a larger molecular machine ruled by integrins. The CD157-integrin partnership provides optimal adhesion and transmigration of human monocytes