Mapping and Functional Role of Phosphorylation Sites in the Thyroid Transcription Factor-1 (TTF-1)

The phosphorylation of thyroid transcription factor-1 (TTF-1), a homeodomain-containing transcription factor that is required for thyroid-specific expression of the thyroglobulin and thyroperoxidase gene promoters, has been studied. Phosphorylation occurs on a maximum of seven serine residues that are distributed in three tryptic peptides. Mutant derivatives of TTF-1, with alanine residues replacing the serines in the phosphorylation sites, have been constructed and used to assess the functional relevance of TTF-1 phosphorylation. The DNA binding activity of TTF-1 appears to be phosphorylation-independent, as indicated also by the performance of TTF-1 purified from an overexpressing Escherichia coli strain. Transcriptional activation by TTF-1 could require phosphorylation only in specific cell types since in a co-transfection assay in heterologous cells both wild-type and mutant proteins show a similar transcriptional activity

Inorganically coated colloidal quantum dots in polar solvents using a microemulsion-assisted method

The dielectric nature of organic ligands capping semiconductor colloidal nanocrystals (NCs) makes them incompatible with optoelectronic applications. For this reason, these ligands are regularly substituted through ligand-exchange processes by shorter (even atomic) or inorganic ones. In this work, an alternative path is proposed to obtain inorganically coated NCs. Differently to regular ligand exchange processes, the method reported here produces core-shell NCs and the removal of the original organic shell in a single step. This procedure leads to the formation of connected NCs resembling 1D worm-like networks with improved optical properties and polar solubility, in comparison with the initial CdSe NCs. The nature of the inorganic shell has been elucidated by X-ray Absorption Near Edge Structure (XANES), Extended X-ray Absorption Fine Structure (EXAFS) and X-ray Photoelectron Spectroscopy (XPS). The 1D morphology along with the lack of long insulating organic ligands and the higher solubility in polar media turns these structures very attractive for their further integration into optoelectronic devices

Non-canonical Wnt signalling regulates scarring in biliary disease via the planar cell polarity receptors

The number of patients diagnosed with chronic bile duct disease is increasing and in most cases these diseases result in chronic ductular scarring, necessitating liver transplantation. The formation of ductular scaring affects liver function; however, scar-generating portal fibroblasts also provide important instructive signals to promote the proliferation and differentiation of biliary epithelial cells. Therefore, understanding whether we can reduce scar formation while maintaining a pro-regenerative microenvironment will be essential in developing treatments for biliary disease. Here, we describe how regenerating biliary epithelial cells express Wnt-Planar Cell Polarity signalling components following bile duct injury and promote the formation of ductular scars by upregulating pro-fibrogenic cytokines and positively regulating collagen-deposition. Inhibiting the production of Wnt-ligands reduces the amount of scar formed around the bile duct, without reducing the development of the pro-regenerative microenvironment required for ductular regeneration, demonstrating that scarring and regeneration can be uncoupled in adult biliary disease and regeneration

The MITF family of transcription factors: Role in endolysosomal biogenesis, Wnt signaling, and oncogenesis

Canonical Wnt signaling influences cellular fate and proliferation through inhibition of Glycogen Synthase Kinase (GSK3) and the subsequent stabilization of its many substrates, most notably β-Catenin, a transcriptional co-activator. MITF, a melanoma oncogene member of the microphthalmia family of transcription factors (MiT), was recently found to contain novel GSK3 phosphorylation sites and to be stabilized by Wnt. Other MiT members, TFEB and TFE3, are known to play important roles in cellular clearance pathways by transcriptionally regulating the biogenesis of lysosomes and autophagosomes via activation of CLEAR elements in gene promoters of target genes. Recent studies suggest that MITF can also upregulate many lysosomal genes. MiT family members are dysregulated in cancer and are considered oncogenes, but the underlying oncogenic mechanisms remain unclear. Here we review the role of MiT members, including MITF, in lysosomal biogenesis, and how cancers overexpressing MITF, TFEB or TFE3 could rewire the lysosomal pathway, inhibit cellular senescence, and activate Wnt signaling by increasing sequestration of negative regulators of Wnt signaling in multivesicular bodies (MVBs). Microarray studies suggest that MITF expression inhibits macroautophagy. In melanoma the MITF-driven increase in MVBs generates a positive feedback loop between MITF, Wnt, and MVBs

HyScreen: A Ground-Based Imaging System for High-Resolution Red and Far-Red Solar-Induced Chlorophyll Fluorescence

Solar-induced chlorophyll fluorescence (SIF) is used as a proxy of photosynthetic efficiency. However, interpreting top-of-canopy (TOC) SIF in relation to photosynthesis remains challenging due to the distortion introduced by the canopy’s structural effects (i.e., fluorescence re-absorption, sunlit-shaded leaves, etc.) and sun–canopy–sensor geometry (i.e., direct radiation infilling). Therefore, ground-based, high-spatial-resolution data sets are needed to characterize the described effects and to be able to downscale TOC SIF to the leafs where the photosynthetic processes are taking place. We herein introduce HyScreen, a ground-based push-broom hyperspectral imaging system designed to measure red ([Formula: see text]) and far-red ([Formula: see text]) SIF and vegetation indices from TOC with single-leaf spatial resolution. This paper presents measurement protocols, the data processing chain and a case study of SIF retrieval. Raw data from two imaging sensors were processed to top-of-canopy radiance by dark-current correction, radiometric calibration, and empirical line correction. In the next step, the improved Fraunhofer line descrimination (iFLD) and spectral-fitting method (SFM) were used for SIF retrieval, and vegetation indices were calculated. With the developed protocol and data processing chain, we estimated a signal-to-noise ratio (SNR) between 50 and 200 from reference panels with reflectance from 5% to 95% and noise equivalent radiance (NER) of 0.04 (5%) to 0.18 (95%) mW m [Formula: see text] sr [Formula: see text] nm [Formula: see text]. The results from the case study showed that non-vegetation targets had SIF values close to 0 mW m [Formula: see text] sr [Formula: see text] nm [Formula: see text] , whereas vegetation targets had a mean [Formula: see text] of 1.13 and [Formula: see text] of 1.96 mW m [Formula: see text] sr [Formula: see text] nm [Formula: see text] from the SFM method. HyScreen showed good performance for SIF retrievals at both [Formula: see text] and [Formula: see text]; nevertheless, we recommend further adaptations to correct for the effects of noise, varying illumination and sensor optics. In conclusion, due to its high spatial resolution, Hyscreen is a promising tool for investigating the relationship between leafs and TOC SIF as well as their relationship with plants’ photosynthetic capacity

Photodetecting Heterostructures from Graphene and Encapsulated Colloidal Quantum Dot Films

Heterostructure devices consisting of graphene and colloidal quantum dots (QDs) have been remarkably successful as photodetectors and have opened the door to technological applications based on the combination of these low-dimensional materials. This work explores the photodetection properties of a heterostructure consisting of a graphene field effect transistor covered by a film of silica-encapsulated colloidal QDs. Defects at the surface of the silica shell trap optically excited charge carriers, which simultaneously enables photodetection via two mechanisms: photogating, resulting in a net p-doping of the device, and Coulombic scattering of charge carriers in the graphene, producing an overall decrease in the current magnitude

Large-Area 2D-0D Heterostructures via Langmuir-Blodgett Film Deposition

The integration of various low dimensional materials into large area, scalable, heterostructures is highly desirable. For example, 0D semiconducting nanocrystals (NCs) exhibit attractive optical emission and absorption properties, while single layer 2D graphene is ideally suited to act as a transparent electrode due to its superior electrical and mechanical properties. The integration of silica encapsulated1, 0D semiconducting NCs with 2D graphene grown by chemical vapor deposition (CVD) is presented in this work. Large area NC films were deposited onto graphene using the Langmuir-Blodgett (LB) method, a technique which allows for the deposition of nanomaterials on a liquid surface. The surface properties of the silica coated NCs necessitated the use of a novel electrospray method (Figure 1a) to successfully spread the NCs2. Large area graphene/NC/graphene (Gr/NC/Gr) heterostructures, seen in Figure 1b, were assembled after film deposition. Topographic, mechanical and electrical properties were investigated using scanning probe techniques and scanning electron microscopy. Photoluminescence (PL) and Raman measurements provided complementary optical and spectroscopic information. The liquid employed in the LB trough was found to be critical for successful film transfer. By using dimethyl sulfoxide instead of water, continuous, homogenous films were obtained which maintained the optical properties of the NCs (Figure 1c). Raman measurements revealed a significant intensity enhancement of the top graphene sheets, along with additional characteristics attributed to the rippling and straining of the graphene on the NC film

Hybrid 2D Membrane-Nanoparticle Heterostructures via Langmuir-Blodgett Deposition

Hybrid graphene-nanocrystal materials have been proposed as promising candidates for a variety of applications, such as energy harvesting and light-emitting devices, due to the electrical properties of graphene and the superb optical properties of semiconducting nanocrystals. In this work, we use hybrid structures of graphene and silica-capped semiconducting nanocrystals as resonant tunnelling devices for unique electrical identification. It has been demonstrated that atomic scale defects in resonant tunnelling diodes lead to measurable shifts in the negative differential resistance peaks in the I-V characteristics. These defects cannot be controlled nor characterised during fabrication and thus act as unique signatures of each individual device. We propose the use of resonant tunnelling, through arrays of quantum dots, to further increase the quantum confinement and uniqueness of such devices. In order to achieve this goal, we prepared silica-capped CdSe/ZnS colloidal nanocrystal thin films via Langmuir-Blodgett deposition on top of a CVD-grown graphene sheet. A second graphene membrane was then transferred on top of the structure to act as the top contact. The silica shell acts as a double tunnelling barrier sandwiching the nanocrystal, the electrons being able to tunnel through the whole structure only when the resonant tunnelling condition is met. To characterise the devices, we performed Raman and photoluminescence spectroscopy in the different stages of the fabrication process, as well as different scanning probe techniques to characterise the topography and the electrical properties of the hybrid structures

Hybrid 2D Membrane-Nanoparticle Heterostructures via Langmuir-Blodgett Deposition

Hybrid graphene-nanocrystal materials have been proposed as promising candidates for a variety of applications, such as energy harvesting and light-emitting devices, due to the electrical properties of graphene and the superb optical properties of semiconducting nanocrystals. In this work, we use hybrid structures of graphene and silica-capped semiconducting nanocrystals as resonant tunnelling devices for unique electrical identification. It has been demonstrated that atomic scale defects in resonant tunnelling diodes lead to measurable shifts in the negative differential resistance peaks in the I-V characteristics. These defects cannot be controlled nor characterised during fabrication and thus act as unique signatures of each individual device. We propose the use of resonant tunnelling, through arrays of quantum dots, to further increase the quantum confinement and uniqueness of such devices. In order to achieve this goal, we prepared silica-capped CdSe/ZnS colloidal nanocrystal thin films via Langmuir-Blodgett deposition on top of a CVD-grown graphene sheet. A second graphene membrane was then transferred on top of the structure to act as the top contact. The silica shell acts as a double tunnelling barrier sandwiching the nanocrystal, the electrons being able to tunnel through the whole structure only when the resonant tunnelling condition is met. To characterise the devices, we performed Raman and photoluminescence spectroscopy in the different stages of the fabrication process, as well as different scanning probe techniques to characterise the topography and the electrical properties of the hybrid structures

The GLASS-JWST Early Release Science Program. I. Survey Design and Release Plans

The GLASS-JWST Early Release Science (hereafter GLASS-JWST-ERS) Program will obtain and make publicly available the deepest extragalactic data of the ERS campaign. It is primarily designed to address two key science questions, namely, "what sources ionized the universe and when?"and "how do baryons cycle through galaxies?", while also enabling a broad variety of first look scientific investigations. In primary mode, it will obtain NIRISS and NIRSpec spectroscopy of galaxies lensed by the foreground Hubble Frontier Field cluster, Abell 2744. In parallel, it will use NIRCam to observe two fields that are offset from the cluster center, where lensing magnification is negligible, and which can thus be effectively considered blank fields. In order to prepare the community for access to this unprecedented data, we describe the scientific rationale, the survey design (including target selection and observational setups), and present pre-commissioning estimates of the expected sensitivity. In addition, we describe the planned public releases of high-level data products, for use by the wider astronomical community