Spatial coherence of light inside three dimensional media

Speckle is maybe the most fundamental interference effect of light in disordered media, giving rise to fascinating physical phenomena and enabling applications in imaging, spectroscopy or cryptography, to name a few. While speckle formed outside a sample is easily measured and analysed, true bulk speckle, as formed inside random media, is difficult to investigate directly due to the obvious issue of physical access. Furthermore, its proper theoretical description poses enormous challenges. Here we report on the first direct measurements of intensity correlations of light inside a disordered medium, using embedded DNA strings decorated with emitters separated by a controlled nanometric distance. Our method provides in situ access to fundamental properties of bulk speckles as their size and polarization degrees of freedom, both of which are found to deviate significantly from theoretical predictions. The deviations are explained, by comparison with rigorous numerical calculations, in terms of correlations among polarization components and non-universal near-field contributions at the nanoscale

Retinoic acid-induced differentiation sensitizes myeloid progenitors cells to ER stress

The clonal expansion of hematopoietic myeloid precursors blocked at different stages of differentiation characterizes the acute myeloid leukemia (AML) phenotype. A subtype of AML, acute promyelocytic leukemia (APL), characterized by the chimeric protein PML-RARα is considered a paradigm of differentiation therapy. In this leukemia subtype the all-trans-retinoic acid (RA)-based treatments are able to induce PML-RARα degradation and leukemic blast terminal differentiation [1-2]. Granulocytic differentiation of APL cells driven by RA triggers a physiological Unfolded Protein Response (UPR), a series of pathways emanating from the ER in case of ER stress, which ensues when higher protein folding activity is required as during differentiation. We show here that, although mild, the ER stress induced by RA is sufficient to render human APL cell lines and primary blasts very sensitive to low doses of Tunicamycin (Tm), an ER stress inducing drug, at doses that are not toxic in the absence of RA. Importantly only human progenitors cells derived from APL patients resulted sensitive to the combined treatment with RA and Tm whereas those obtained from healthy donors were not affected. We also show that the UPR pathway downstream of PERK plays a major protective role against ER stress in differentiating cells and, by using a specific PERK inhibitor, we potentiated the toxic effect of the combination of RA and Tm. In conclusion, our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML

The hydrogen-bond collective dynamics in liquid methanol

The relatively simple molecular structure of hydrogen-bonded (HB) systems is often belied by their exceptionally complex thermodynamic and microscopic behaviour. For this reason, after a thorough experimental, computational and theoretical scrutiny, the dynamics of molecules in HB systems still eludes a comprehensive understanding. Aiming at shedding some insight into this topic, we jointly used neutron Brillouin scattering and molecular dynamics simulations to probe the dynamics of a prototypical hydrogen-bonded alcohol, liquid methanol. The comparison with the most thoroughly investigated HB system, liquid water, pinpoints common behaviours of their THz microscopic dynamics, thereby providing additional information on the role of HB dynamics in these two systems. This study demonstrates that the dynamic behaviour of methanol is much richer than what so far known, and prompts us to establish striking analogies with the features of liquid and supercooled water. In particular, based on the strong differences between the structural properties of the two systems, our results suggest that the assignment of some dynamical properties to the tetrahedral character of water structure should be questioned. We finally highlight the similarities between the characteristic decay times of the time correlation function, as obtained from our data and the mean lifetime of hydrogen bond known in literature

Switching off hydrogen-bond-driven excitation modes in liquid methanol

Abstract Hydrogen bonding plays an essential role on intermolecular forces, and consequently on the thermodynamics of materials defined by this elusive bonding character. It determines the property of a vital liquid as water as well as many processes crucial for life. The longstanding controversy on the nature of the hydrogen bond (HB) can be settled by looking at the effect of a vanishing HB interaction on the microscopic properties of a given hydrogen-bonded fluid. This task suits the capabilities of computer simulations techniques, which allow to easily switch off HB interactions. We then use molecular dynamics to study the microscopic properties of methanol, a prototypical HB liquid. Fundamental aspects of the dynamics of methanol at room temperature were contextualised only very recently and its rich dynamics was found to have striking analogies with that of water. The lower temperature (200 K) considered in the present study led us to observe that the molecular centre-of-mass dynamics is dominated by four modes. Most importantly, the computational ability to switch on and off hydrogen bonds permitted us to identify which, among these modes, have a pure HB-origin. This clarifies the role of hydrogen bonds in liquid dynamics, disclosing new research opportunities and unexplored interpretation schemes

Pressure-induced amorphization and existence of molecular and polymeric amorphous forms in dense SO2

We report here a study of reversible pressure-induced structural transformation between two amorphous forms of SO$_2$: molecular at pressures below 26 GPa and polymeric above this pressure, at temperatures of 77 - 300 K. The transformation was observed by Raman spectroscopy and x-ray diffraction in a diamond anvil cell. The same phenomenon was also observed in ab initio molecular dynamics simulations where both forward and reverse transitions were detected, allowing to analyze in detail the atomic structure of both phases. The high-pressure polymeric amorphous form was found to consist mainly of disordered polymeric chains made of 3-coordinated sulfur atoms connected via oxygen atoms, and few residual intact molecules. The simulation results are in good agreement with experimental data. Our observations suggest a possible existence of molecular liquid - polymeric liquid transition in SO$_2$ and show a case example of polyamorphism in system consisting of simple molecules with multiple bonds.Comment: 8 pages, 4 figures, supplementary materia

The mutant p53-ID4 complex controls VEGFA isoforms by recruiting lncRNA MALAT1

The abundant, nuclear-retained, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) has been associated with a poorly differentiated and aggressive phenotype of mammary carcinomas. This long non-coding RNA (lncRNA) localizes to nuclear speckles, where it interacts with a subset of splicing factors and modulates their activity. In this study, we demonstrate that oncogenic splicing factor SRSF1 bridges MALAT1 to mutant p53 and ID4 proteins in breast cancer cells. Mutant p53 and ID4 delocalize MALAT1 from nuclear speckles and favor its association with chromatin. This enables aberrant recruitment of MALAT1 on VEGFA pre-mRNA and modulation of VEGFA isoforms expression. Interestingly, VEGFA-dependent expression signatures associate with ID4 expression specifically in basal-like breast cancers carrying TP53 mutations. Our results highlight the key role for MALAT1 in control of VEGFA isoforms expression in breast cancer cells expressing gain-of-function mutant p53 and ID4 proteins

Study protocol on advance care planning in multiple sclerosis (ConCure-SM): intervention construction and multicentre feasibility trial

Multiple sclerosis (MS) is the most common cause of progressive neurological disability in young adults. The use of advance care planning (ACP) for people with progressive MS (pwPMS) remains limited. The ConCure-SM project aims to assess the effectiveness of a structured ACP intervention for pwPMS. The intervention consists of a training programme on ACP for healthcare professionals caring for pwPMS, and a booklet to be used during the ACP conversation. Herein, we describe the first two project phases

Retinoic Acid-induced differentiation sensitizes myeloid progenitors cells to ER stress

The clonal expansion of hematopoietic myeloid precursors blocked at different stages of differentiation characterizes the acute myeloid leukemia (AML) phenotype. A subtype of AML, acute promyelocytic leukemia (APL), characterized by the chimeric protein PML-RARα is considered a paradigm of differentiation therapy. In this leukemia subtype the all-trans-retinoic acid (RA)-based treatments are able to induce PML-RARα degradation and leukemic blast terminal differentiation [1-2]. Granulocytic differentiation of APL cells driven by RA triggers a physiological Unfolded Protein Response (UPR), a series of pathways emanating from the ER in case of ER stress, which ensues when higher protein folding activity is required as during differentiation. We show here that, although mild, the ER stress induced by RA is sufficient to render human APL cell lines and primary blasts very sensitive to low doses of Tunicamycin (Tm), an ER stress inducing drug, at doses that are not toxic in the absence of RA. Importantly only human progenitors cells derived from APL patients resulted sensitive to the combined treatment with RA and Tm whereas those obtained from healthy donors were not affected. We also show that the UPR pathway downstream of PERK plays a major protective role against ER stress in differentiating cells and, by using a specific PERK inhibitor, we potentiated the toxic effect of the combination of RA and Tm. In conclusion, our findings identify the ER stress-related pathways as potential targets in the search for novel therapeutic strategies in AML