Mie-resonances, infrared emission and band gap of InN

Mie resonances due to scattering/absorption of light in InN containing clusters of metallic In may have been erroneously interpreted as the infrared band gap absorption in tens of papers. Here we show by direct thermally detected optical absorption measurements that the true band gap of InN is markedly wider than currently accepted 0.7 eV. Micro-cathodoluminescence studies complemented by imaging of metallic In have shown that bright infrared emission at 0.7-0.8 eV arises from In aggregates, and is likely associated with surface states at the metal/InN interfaces.Comment: 4 pages, 5 figures, submitted to PR

Free carrier effects in gallium nitride epilayers: the valence band dispersion

The dispersion of the A-valence-band in GaN has been deduced from the observation of high-index magneto-excitonic states in polarised interband magneto-reflectivity and is found to be strongly non-parabolic with a mass in the range 1.2-1.8 m_{e}. It matches the theory of Kim et al. [Phys. Rev. B 56, 7363 (1997)] extremely well, which also gives a strong k-dependent A-valence-band mass. A strong phonon coupling leads to quenching of the observed transitions at an LO-phonon energy above the band gap and a strong non-parabolicity. The valence band was deduced from subtracting from the reduced dispersion the electron contribution with a model that includes a full treatment of the electron-phonon interaction.Comment: Revtex, 4 pages, 5 figure

Strain-free bulk-like GaN grown by hydride-vapor-phase-epitaxy on two-step epitaxial lateral overgrown GaN template

Crack-free bulk-like GaN with high crystalline quality has been obtained by hydride-vapor-phase-epitaxy (HVPE)growth on a two-step epitaxial lateral overgrown GaN template on sapphire. During the cooling down stage, the as-grown 270-μm-thick GaN layer was self-separated from the sapphire substrate. Plan-view transmission electron microscopyimages show the dislocation density of the free-standing HVPE-GaN to be ∼2.5×10 exp 7  cm exp −2 on the Ga-polar face. A low Ga vacancy related defect concentration of about 8×10 exp 15 cm exp−3 is extracted from positron annihilation spectroscopy data. The residual stress and the crystalline quality of the material are studied by two complementary techniques. Low-temperature photoluminescence spectra show the main neutral donor bound exciton line to be composed of a doublet structure at 3.4715 (3.4712) eV and 3.4721 (3.4718) eV for the Ga- (N-) polar face with the higher-energy component dominating. These line positions suggest virtually strain-free material on both surfaces with high crystalline quality as indicated by the small full width at half maximum values of the donor bound exciton lines. The E1(TO) phonon mode position measured at 558.52 cm exp −1 (Ga face) by infrared spectroscopic ellipsometry confirms the small residual stress in the material, which is hence well suited to act as a lattice-constant and thermal-expansion-coefficient matched substrate for further homoepitaxy, as needed for high-quality III-nitride device applications.Peer reviewe

Genetic regulation of pituitary gland development in human and mouse

Normal hypothalamopituitary development is closely related to that of the forebrain and is dependent upon a complex genetic cascade of transcription factors and signaling molecules that may be either intrinsic or extrinsic to the developing Rathke’s pouch. These factors dictate organ commitment, cell differentiation, and cell proliferation within the anterior pituitary. Abnormalities in these processes are associated with congenital hypopituitarism, a spectrum of disorders that includes syndromic disorders such as septo-optic dysplasia, combined pituitary hormone deficiencies, and isolated hormone deficiencies, of which the commonest is GH deficiency. The highly variable clinical phenotypes can now in part be explained due to research performed over the last 20 yr, based mainly on naturally occurring and transgenic animal models. Mutations in genes encoding both signaling molecules and transcription factors have been implicated in the etiology of hypopituitarism, with or without other syndromic features, in mice and humans. To date, mutations in known genes account for a small proportion of cases of hypopituitarism in humans. However, these mutations have led to a greater understanding of the genetic interactions that lead to normal pituitary development. This review attempts to describe the complexity of pituitary development in the rodent, with particular emphasis on those factors that, when mutated, are associated with hypopituitarism in humans

Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations

© The Author(s), 2021. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Priscu, J. C., Kalin, J., Winans, J., Campbell, T., Siegfried, M. R., Skidmore, M., Dore, J. E., Leventer, A., Harwood, D. M., Duling, D., Zook, R., Burnett, J., Gibson, D., Krula, E., Mironov, A., McManis, J., Roberts, G., Rosenheim, B. E., Christner, B. C., Kasic, K., Fricker, H. A., Lyons, W. B., Barker, J., Bowling, M., Collins, B., Davis, C., Gagnon, A., Gardner, C., Gustafson, C., Kim, O-S., Li, W., Michaud, A., Patterson, M. O., Tranter, M., Ryan Venturelli, R., Trista Vick-Majors, T., & Elsworth, C. Scientific access into Mercer Subglacial Lake: scientific objectives, drilling operations and initial observations. Annals of Glaciology, 62(85–86), (2021): 340–352, https://doi.org/10.1017/aog.2021.10.The Subglacial Antarctic Lakes Scientific Access (SALSA) Project accessed Mercer Subglacial Lake using environmentally clean hot-water drilling to examine interactions among ice, water, sediment, rock, microbes and carbon reservoirs within the lake water column and underlying sediments. A ~0.4 m diameter borehole was melted through 1087 m of ice and maintained over ~10 days, allowing observation of ice properties and collection of water and sediment with various tools. Over this period, SALSA collected: 60 L of lake water and 10 L of deep borehole water; microbes >0.2 μm in diameter from in situ filtration of ~100 L of lake water; 10 multicores 0.32–0.49 m long; 1.0 and 1.76 m long gravity cores; three conductivity–temperature–depth profiles of borehole and lake water; five discrete depth current meter measurements in the lake and images of ice, the lake water–ice interface and lake sediments. Temperature and conductivity data showed the hydrodynamic character of water mixing between the borehole and lake after entry. Models simulating melting of the ~6 m thick basal accreted ice layer imply that debris fall-out through the ~15 m water column to the lake sediments from borehole melting had little effect on the stratigraphy of surficial sediment cores.This material is based upon work supported by the US National Science Foundation, Section for Antarctic Sciences, Antarctic Integrated System Science program as part of the interdisciplinary (Subglacial Antarctic Lakes Scientific Access (SALSA): Integrated study of carbon cycling in hydrologically-active subglacial environments) project (NSF-OPP 1543537, 1543396, 1543405, 1543453 and 1543441). Ok-Sun Kim was funded by the Korean Polar Research Institute. We are particularly thankful to the SALSA traverse personnel for crucial technical and logistical support. The United States Antarctic Program enabled our fieldwork; the New York Air National Guard and Kenn Borek Air provided air support; UNAVCO provided geodetic instrument support. Hot water drilling activities, including repair and upgrade modifications of the WISSARD hot water drill system, for the SALSA project were supported by a subaward from the Ice Drilling Program of Dartmouth College (NSF-PLR 1327315) to the University of Nebraska-Lincoln. J. Lawrence assisted with manuscript preparation. Finally, we are grateful to C. Dean, the SALSA Project Manager, and R. Ricards, SALSA Project Coordinator at McMurdo Station, for their organizational skills, and B. Huber of Lamont-Doherty Earth Observatory for providing the SBE39 PT sensors and the Nortek Aquadopp current meter and assisting with interpretation of the data. B. Huber also provided helpful input on programing and calibrating the SBE19PlusV2 6112 CTD

A GRFa2/Prop1/Stem (GPS) Cell Niche in the Pituitary

BACKGROUND: The adult endocrine pituitary is known to host several hormone-producing cells regulating major physiological processes during life. Some candidates to progenitor/stem cells have been proposed. However, not much is known about pituitary cell renewal throughout life and its homeostatic regulation during specific physiological changes, such as puberty or pregnancy, or in pathological conditions such as tumor development. PRINCIPAL FINDINGS: We have identified in rodents and humans a niche of non-endocrine cells characterized by the expression of GFRa2, a Ret co-receptor for Neurturin. These cells also express b-Catenin and E-cadherin in an oriented manner suggesting a planar polarity organization for the niche. In addition, cells in the niche uniquely express the pituitary-specific transcription factor Prop1, as well as known progenitor/stem markers such as Sox2, Sox9 and Oct4. Half of these GPS (GFRa2/Prop1/Stem) cells express S-100 whereas surrounding elongated cells in contact with GPS cells express Vimentin. GFRa2+-cells form non-endocrine spheroids in culture. These spheroids can be differentiated to hormone-producing cells or neurons outlining the neuroectoderm potential of these progenitors. In vivo, GPSs cells display slow proliferation after birth, retain BrdU label and show long telomeres in its nuclei, indicating progenitor/stem cell properties in vivo. SIGNIFICANCE: Our results suggest the presence in the adult pituitary of a specific niche of cells characterized by the expression of GFRa2, the pituitary-specific protein Prop1 and stem cell markers. These GPS cells are able to produce different hormone-producing and neuron-like cells and they may therefore contribute to postnatal pituitary homeostasis. Indeed, the relative abundance of GPS numbers is altered in Cdk4-deficient mice, a model of hypopituitarism induced by the lack of this cyclin-dependent kinase. Thus, GPS cells may display functional relevance in the physiological expansion of the pituitary gland throughout life as well as protection from pituitary disease

Detecting intratumoral heterogeneity of EGFR activity by liposome-based in vivo transfection of a fluorescent biosensor

Despite decades of research in the epidermal growth factor receptor (EGFR) signalling field, and many targeted anti-cancer drugs that have been tested clinically, the success rate for these agents in the clinic is low, particularly in terms of the improvement of overall survival. Intratumoral heterogeneity is proposed as a major mechanism underlying treatment failure of these molecule-targeted agents. Here we highlight the application of fluorescence lifetime microscopy (FLIM)-based biosensing to demonstrate intratumoral heterogeneity of EGFR activity. For sensing EGFR activity in cells, we used a genetically encoded CrkII-based biosensor which undergoes conformational changes upon tyrosine-221 phosphorylation by EGFR. We transfected this biosensor into EGFR-positive tumour cells using targeted lipopolyplexes bearing EGFR-binding peptides at their surfaces. In a murine model of basal-like breast cancer, we demonstrated a significant degree of intratumoral heterogeneity in EGFR activity, as well as the pharmacodynamic effect of a radionuclide-labeled EGFR inhibitor in situ. Furthermore, a significant correlation between high EGFR activity in tumour cells and macrophage-tumour cell proximity was found to in part account for the intratumoral heterogeneity in EGFR activity observed. The same effect of macrophage infiltrate on EGFR activation was also seen in a colorectal cancer xenograft. In contrast, a non-small cell lung cancer xenograft expressing a constitutively active EGFR conformational mutant exhibited macrophage proximity-independent EGFR activity. Our study validates the use of this methodology to monitor therapeutic response in terms of EGFR activity. In addition, we found iNOS gene induction in macrophages that are cultured in tumour cell-conditioned media as well as an iNOS activity-dependent increase in EGFR activity in tumour cells. These findings point towards an immune microenvironment-mediated regulation that gives rise to the observed intratumoral heterogeneity of EGFR signalling activity in tumour cells in vivo

Mutations in the nuclear localization sequence of the Aristaless related homeobox; sequestration of mutant ARX with IPO13 disrupts normal subcellular distribution of the transcription factor and retards cell division

The electronic version of this article is the complete one and can be found online at: http://www.pathogeneticsjournal.com/content/3/1/1Background: Aristaless related homeobox (ARX) is a paired-type homeobox gene. ARX function is frequently affected by naturally occurring mutations. Nonsense mutations, polyalanine tract expansions and missense mutations in ARX cause a range of intellectual disability and epilepsy phenotypes with or without additional features including hand dystonia, lissencephaly, autism or dysarthria. Severe malformation phenotypes, such as X-linked lissencephaly with ambiguous genitalia (XLAG), are frequently observed in individuals with protein truncating or missense mutations clustered in the highly conserved paired-type homeodomain. Results: We have identified two novel point mutations in the R379 residue of the ARX homeodomain; c.1135C>A, p.R379S in a patient with infantile spasms and intellectual disability and c.1136G>T, p.R379L in a patient with XLAG. We investigated these and other missense mutations (R332P, R332H, R332C, T333N: associated with XLAG and Proud syndrome) predicted to affect the nuclear localisation sequences (NLS) flanking either end of the ARX homeodomain. The NLS regions are required for correct nuclear import facilitated by Importin 13 (IPO13). We demonstrate that missense mutations in either the N- or C-terminal NLS regions of the homeodomain cause significant disruption to nuclear localisation of the ARX protein in vitro. Surprisingly, none of these mutations abolished the binding of ARX to IPO13. This was confirmed by co-immunoprecipitation and immmuno fluorescence studies. Instead, tagged and endogenous IPO13 remained bound to the mutant ARX proteins, even in the RanGTP rich nuclear environment. We also identify the microtubule protein TUBA1A as a novel interacting protein for ARX and show cells expressing mutant ARX protein accumulate in mitosis, indicating normal cell division may be disrupted. Conclusions: We show that the most likely, common pathogenic mechanism of the missense mutations in NLS regions of the ARX homeodomain is inadequate accumulation and distribution of the ARX transcription factor within the nucleus due to sequestration of ARX with IPO13.Cheryl Shoubridge, May Huey Tan, Tod Fullston, Desiree Cloosterman, David Coman, George McGillivray, Grazia M Mancini, Tjitske Kleefstra and Jozef Géc