The role of histidine in the mechanism of iron release from human serum transferrin

The role of non-coordinated histidines in the iron release mechanism of human serum transferrin has been investigated by chemical modification of the protein with ethoxyformic anhydride and aquopentaamine ruthenium(II), reagents specific for histidines under mild conditions. Kinetic studies of the iron release reaction at pH 5 under the action of different mediators e.g., PPi, Pi, Cit, ATP, GTP, and DPG, show that ethoxyformic anhydride imparts increased stability to the protein with rate constants for the C-terminal site decreased by factors from 2 to 10. The largest effects were seen with intracellular iron chelators GTP and DPG. A protonated imidazole group near the metal perhaps serves as a binding site for the triphosphate chelators. The binding of such chelators to a nearby histidine may assist in the formation of a quaternary intermediate of the type Chel-Fe-Transferrin-HCO\sb3 prior to release of iron. Modification using aquopentaamine ruthenium(II) a reagent for surface accessible histidine residues, enhances the rate of release from the N-terminal site but has no effect the C-terminal site. The Tsou Chen-Lu statistical method used to analyze the rate data suggests the involvement of two histidines in the N-terminal lobe not conserved in the C-terminal lobe. These results may explain the kinetic liability of the N-terminal site relative to the C-terminal site in acidic solutions. The distance between the metal site and nearby histidines was calculated from fluorescence energy transfer measurements using Tb(III) in the iron(III) binding site as the donor and pentaamine ruthenium(III) modified histidines as the acceptor chromophore. The fluorescence measurements imply two histidines in each lobe are responsible for quenching of the Tb(III) emission. Using upper and lower limits for the index of refraction and quantum yield and assuming the energy transfer follows parallel first order kinetics, a donor-acceptor distance between 1.32 nm and 1.42 nm was obtained

Irreducible subgroups of algebraic groups

A closed subgroup of a semisimple algebraic group G is said to be G‐irreducible if it lies in no proper parabolic subgroup of G. We prove a number of results concerning such subgroups. Firstly they have only finitely many overgroups in G; secondly, with some specified exceptions, there exist G‐irreducible subgroups of type A1; and thirdly, we prove an embedding theorem for G‐irreducible subgroup

Reversibility of Serum Removal Effects on IGF-II mRNA in Human Neuroblastoma Cells

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73527/1/j.1749-6632.1993.tb26227.x.pd

Axial level‐specific regulation of neuronal development: Lessons from PITX2

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/109833/1/jnr23471.pd

Multiplicity-free representations of algebraic groups II

We continue our work (started in ``Multiplicity-free representations of algebraic groups", arXiv:2101.04476), on the program of classifying triples $(X,Y,V)$, where $X,Y$ are simple algebraic groups over an algebraically closed field of characteristic zero with $X<Y$, and $V$ is an irreducible module for $Y$ such that the restriction $V\downarrow X$ is multiplicity-free. In this paper we handle the case where $X$ is of type $A$, and is irreducibly embedded in $Y$ of type $B,C$ or $D$. It turns out that there are relatively few triples for $X$ of arbitrary rank, but a number of interesting exceptional examples arise for small ranks.Comment: 60 page

Chromodomain proteins in development: lessons from CHARGE syndrome

Layman WS, Hurd EA, Martin DM. Chromodomain proteins in development: lessons from CHARGE syndrome.In humans, heterozygous mutations in the adenosine triphosphate-dependent chromatin remodeling gene CHD7 cause CHARGE syndrome, a common cause of deaf–blindness, balance disorders, congenital heart malformations, and olfactory dysfunction with an estimated incidence of approximately 1 in 10,000 newborns. The clinical features of CHARGE in humans and mice are highly variable and incompletely penetrant, and most mutations appear to result in haploinsufficiency of functional CHD7 protein. Mice with heterozygous loss of function mutations in Chd7 are a good model for CHARGE syndrome, and analyses of mouse mutant phenotypes have begun to clarify a role for CHD7 during development and into adulthood. Chd7 heterozygous mutant mice have postnatal delayed growth, inner ear malformations, anosmia/hyposmia, and craniofacial defects, and Chd7 homozygous mutants are embryonic lethal. A central question in developmental biology is how chromodomain proteins like CHD7 regulate important developmental processes, and whether they directly activate or repress downstream gene transcription or act more globally to alter chromatin structure and/or function. CHD7 is expressed in a wide variety of tissues during development, suggesting that it has tissue-specific and developmental stage-specific roles. Here, we review recent and ongoing analyses of CHD7 function in mouse models and cell-based systems. These studies explore tissue-specific effects of CHD7 deficiency, known CHD7 interacting proteins, and downstream target sites for CHD7 binding. CHD7 is emerging as a critical regulator of important developmental processes in organs affected by human CHARGE syndrome.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79089/1/j.1399-0004.2010.01446.x.pd

Chromodomain Helicase DNA-Binding Proteins in Stem Cells and Human Developmental Diseases

Dynamic regulation of gene expression is vital for proper cellular development and maintenance of differentiated states. Over the past 20 years, chromatin remodeling and epigenetic modifications of histones have emerged as key controllers of rapid reversible changes in gene expression. Mutations in genes encoding enzymes that modify chromatin have also been identified in a variety of human neurodevelopmental disorders, ranging from isolated intellectual disability and autism spectrum disorder to multiple congenital anomaly conditions that affect major organ systems and cause severe morbidity and mortality. In this study, we review recent evidence that chromodomain helicase DNA-binding (CHD) proteins regulate stem cell proliferation, fate, and differentiation in a wide variety of tissues and organs. We also highlight known roles of CHD proteins in human developmental diseases and present current unanswered questions about the pleiotropic effects of CHD protein complexes, their genetic targets, nucleosome sliding functions, and enzymatic effects in cells and tissues.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140206/1/scd.2014.0544.pd

Interferon-Γ inhibits DNA synthesis and insulin-like growth factor-II expression in human neuroblastoma cells

Interferon-Γ (IFN-Γ) is known to be an antiproliferative, differentiation agent in many cell types, including neuroblastoma. In this study, we determined the effects of IFN-Γ on cellular growth and expression of insulin-like growth factor II (IGF-II) and IGF receptors in the human neuroblastoma cell line SH-SY5Y. Incubation of SH-SY5Y cells in IFN-Γ (20–100 U/ml) induced the formation of long neuritic processes. IFN-Γ treatment also induced decreases in [ 3 H]TdR incorporation, as well as serum-dependent changes in cell number. Treatment with IFN-Γ reduced cell number 33% in the presence of serum but had no effect on cell number in the absence of serum. IGF-II mRNA content was 60% inhibited by IFN-Γ, and was not serum dependent. The concentration of immunoreactive IGF-II in SH-SY5Y conditioned medium was also reduced in the presence of IFN-Γ, to less than half of control levels. In contrast, type I IGF receptor mRNA content was increased more than three-fold after treatment with IFN-Γ and serum. Co-incubation in IFN-Γ (20–100 U/ml) and IGF-II on (3–10 nM) prevented the inhibitory effects of IFN-Γ on [ 3 H]TdR ncorporation in serum-free media. Our results suggest that IFN-Γ may inhibit DNA synthesis and cell growth by interfering with an IGF-II/type I IGF receptor autocrine growth or survival mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/50226/1/490340502_ftp.pd

PEMBENTUKAN DAN PEMILIHAN PEMIMPIN GEREJA YANG BERKUALITAS

This article discusses the qualities of Christian leaders and leadership in the era of globalization. Globalization is marked by advances in knowledge, technology and advances in social media. To find out how the quality of Christian leaders and leadership is in the Globalization Era, the author conducted research using a qualitative research approach, namely by using materials and information as well as document research related to Christian leaders and leadership. From the results of the research conducted, it is known that the quality of Christian leaders and leadership has been degraded due to manipulation in the selection of leaders, the lack of sensitivity of the church in preparing church leaders, and the low spirituality of Christian leaders so that it has an influence on the quality of Christian leaders and leadership. From the results of this study, the authors provide solutions for the formation of quality Christian leaders and solutions to the selection of Christian leadership because formation without proper leadership selection will not produce quality leaders and leadership