Civil Rights
Movements, leaders, victories and the continuing fight for equality.
q2K BHP
Black History Portal
THE BHP WIRE —
HIDDEN TRUTHS
What's New!
Explore the people, places, events, achievements, struggles and stories that shaped our journey.
Movements, leaders, victories and the continuing fight for equality.
Innovation, patents, science, technology and world-changing contributions.
Pioneers, champions, Negro Leagues, records, activism and excellence.
Meet the people whose lives, choices and achievements shaped the journey.
Black towns, communities, institutions and places where history happened.
Moments that changed communities, movements, institutions and the nation.
Wilmington, North Carolina once had a thriving Black middle class and an elected interracial government. In 1898 white supremacists used violence to overthrow that government, kill Black residents and drive many others from the city.
MORE →Reflects the personal views, recollections, and perspective of the author, Mike Davis.
This is a personal recollection on the Move fire on May 13, 1985
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene.[5] The protein encoded by this gene is a transcription factor.[6]
GLI2 belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis.[7]
There are four isoforms: Gli2 alpha, beta, gamma and delta.[8]
C-terminal activator and N-terminal repressor regions have been identified in both Gli2 and Gli3.[9] However, the N-terminal part of human Gli2 is much smaller than its mouse or frog homologs, suggesting that it may lack repressor function.
Gli2 affects ventroposterior mesodermal development by regulating at least three different genes; Wnt genes involved in morphogenesis, Brachyury genes involved in tissue specification and Xhox3 genes involved in positional information.[10] The anti-apoptotic protein BCL-2 is up regulated by Gli2 and, to a lesser extent, Gli1 – but not Gli3, which may lead to carcinogenesis.[11] Additionally, in the amphibian model organism Xenopus laevis, it has been shown that Gli2 plays a key role in the induction, specification, migration and differentiation of the neural crest.[12] In this context, Gli2 is responding to the Indian Hedgehog signaling pathway.[13]
It has been shown in mouse models that Gli1 can compensate for knocked out Gli2 function when expressed from the Gli2 locus. This suggests that in mouse embryogenesis, Gli1 and Gli2 regulate a similar set of target genes. Mutations do develop later in development suggesting Gli1/Gli2 transcriptional regulation is context dependent.[11] Gli2 and Gli3 are important in the formation and development of lung, trachea and oesophagus tissue during embryo development.[14] Studies have also shown that GLI2 plays a dual role as activator of keratinocyte proliferation and repressor of epidermal differentiation.[15] There is a significant level of crosstalk and functional overlap between the Gli TFs. Gli2 has been shown to compensate for the loss of Gli1 in transgenic Gli1-/- mice which are phenotypically normal.[14] However, loss of Gli3 leads to abnormal patterning and loss of Gli2 affects the development of ventral cell types, most significantly in the floor plate. Gli2 has been shown to compensate for Gli1 ventrally and Gli3 dorsally in transgenic mice.[16] Gli2 null mice embryos develop neural tube defects which, can be rescued by overexpression of Gli1 (Jacob and Briscoe, 2003). Gli1 has been shown to induce the two GLI2 α/β isoforms.
Transgenic double homozygous Gli1-/- and Gli2-/- knockout mice display serious central nervous system and lung defects have small lungs, undescended testes, and a hopping gait as well as an extra postaxial nubbin on the limbs.[17] Gli2-/- and Gli3-/- double homozygous transgenic mice are not viable and do not survive beyond embryonic level.[14][18][19] These studies suggest overlapping roles for Gli1 with Gli2 and Gli2 with Gli3 in embryonic development.
Transgenic Gli1-/- and Gli2-/- mice have a similar phenotype to transgenic Gli1 gain of function mice. This phenotype includes failure to thrive, early death, and a distended gut although no tumors form in transgenic Gli1-/- and Gli2-/- mice. This could suggest that overexpression of human Gli1 in the mouse may have led to a dominant negative rather than a gain-of-function phenotype.[20]
Transgenic mice over-expressing the transcription factor Gli2 under the K5 promoter in cutaneous keratinocytes develop multiple skin tumours on the ears, tail, trunk and dorsal aspect of the paw, resembling those of basal cell carcinoma (BCC). Unlike Gli1 transgenic mice, Gli2 transgenic mice only developed BCC-like tumors. Transgenic mice with N-terminal deletion of Gli2, developed the benign trichoblastomas, cylindromas and hamartomas but rarely developed BCCs.[21] Gli2 is expressed in the interfollicular epidermis and the outer root sheath of hair follicles in normal human skin. This is significant as Shh regulates hair follicle growth and morphogenesis. When inappropriately activated causes hair follicle derived tumors, the most clinically significant being the BCC.[22]
Of the four Gli2 isoforms the expression of Gli2beta mRNA was increased the most in BCCs. Gli2beta is an isoform spliced at the first splicing site which contains a repression domain and consists of an intact activation domain. Overexpression of this Gli2 splice variant may lead to the upregulation of the Shh signalling pathway, thereby inducing BCCs.[8]
Mutations of the GLI2 gene are associated with midline craniofacial anomalies, hypopituitarism, and sometimes holoprosencephaly (https://omim.org/entry/165230, Holoprosencephaly 9, Culler-Jones syndrome)[7]
In human keratinocytes Gli2 activation upregulates a number of genes involved in cell cycle progression including E2F1, CCND1, CDC2 and CDC45L. Gli2 is able to induce G1–S phase progression in contact-inhibited keratinocytes which may drive tumour development.[15]
Although both Gli1 and Gl12 have been implicated it is unclear whether one or both are needed for carcinogenesis. However, due to feed back loops, one may directly or indirectly induce the other.
Minhas et al. 2015 have recently elucidated a subset of cis-regulatory elements controlling GLI2 expression. They have shown that conserved non-coding elements (CNEs) from the intron of GLI2 gene act as tissue-specific enhancers and reporter gene expression induced by these elements correlates with previously reported endogenous gli2 expression in zebrafish. The regulatory activities of these elements are observed in several embryonic domains, including neural tube and pectoral fin.[23]
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
Source: Wikipedia. Article content is retrieved live through the MediaWiki API.
Zinc finger protein GLI2 also known as GLI family zinc finger 2 is a protein that in humans is encoded by the GLI2 gene. The protein encoded by this gene is a transcription factor. GLI2 belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis.
GLI may refer to: Gaming Laboratories International Getty Leadership Institute at Claremont Graduate University Glen Innes Airport, in New South Wales, Australia Global Labour Institute, a British workers rights organization Great Lakes Initiative, a fictional superhero team Great Lakes Invitational, a college ice hockey tournament Greater Louisville Inc., an American business development organization Greyhound Lines, a North-American bus carrier Volkswagen GLI, an automobile GLI1, GLI2, GLI3, glioma-associated family of transcription factors
In a dynamical system, bistability means the system has two stable equilibrium states. A bistable structure can be resting in either of two states. An example of a mechanical device which is bistable is a light switch. The switch lever is designed to rest in the "on" or "off" position, but not between the two. Bistable behavior can occur in mechanical linkages, electronic circuits, nonlinear optical systems, chemical reactions, and physiological and biological systems. In a conservative force field, bistability stems from the fact that the potential energy has two local minima, which are the stable equilibrium points. These rest states need not have equal potential energy. By mathematical arguments, a local maximum, an unstable equilibrium point, must lie between the two minima. At rest, a particle will be in one of the minimum equilibrium positions, because that corresponds to the state of lowest energy. The maximum can be visualized as a barrier between them. A system can transition from one state of minimal energy to the other if it is given enough activation energy to penetrate the barrier (compare activation energy and Arrhenius equation for the chemical case). After the barrier has been reached, assuming the system has damping, it will relax into the other minimum state in a time called the relaxation time. Bistability is widely used in digital electronics devices to store binary data. It is the essential characteristic of the flip-flop, a circuit which is a fundamental building block of computers and some types of semiconductor memory. A bistable device can store one bit of binary data, with one state representing a "0" and the other state a "1". It is also used in relaxation oscillators, multivibrators, and the Schmitt trigger. Optical bistability is an attribute of certain optical devices where two resonant transmissions states are possible and stable, dependent on the input. Bistability can also arise in biochemical systems, where it creates digital, switch-like outputs from the constituent chemical concentrations and activities. It is often associated with hysteresis in such systems.
Cellular differentiation, also known as cellular specification, is the process in which a stem cell changes from one type to a differentiated one. Usually, the cell changes to a more specialized type. Differentiation happens multiple times during the development of a multicellular organism as it changes from a simple zygote to a complex system of tissues and cell types. Differentiation continues in adulthood as adult stem cells divide and create fully differentiated daughter cells during tissue repair and during normal cell turnover. Some differentiation occurs in response to antigen exposure. Differentiation dramatically changes a cell's size, shape, membrane potential, metabolic activity, and responsiveness to signals. These changes are largely due to highly controlled modifications in gene expression and are the study of epigenetics. With a few exceptions, cellular differentiation almost never involves a change in the DNA sequence itself. Metabolic composition, however, gets dramatically altered where stem cells are characterized by abundant metabolites with highly unsaturated structures whose levels decrease upon differentiation. Thus, different cells can have very different physical characteristics despite having the same genome. A specialized type of differentiation, known as terminal differentiation, is of importance in some tissues, including vertebrate nervous system, striated muscle, epidermis and gut. During terminal differentiation, a precursor cell formerly capable of cell division permanently leaves the cell cycle, dismantles the cell cycle machinery and often expresses a range of genes characteristic of the cell's final function (e.g. myosin and actin for a muscle cell). Differentiation may continue to occur after terminal differentiation if the capacity and functions of the cell undergo further changes. Among dividing cells, there are multiple levels of cell potency, which is the cell's ability to differentiate into other cell types. A greater potency indicates a larger number of cell types that can be derived. A cell that can differentiate into all cell types, including the placental tissue, is known as totipotent. In mammals, only the zygote and subsequent blastomeres are totipotent, while in plants, many differentiated cells can become totipotent with simple laboratory techniques. A cell that can differentiate into all cell types of the adult organism is known as pluripotent. Such cells are called meristematic cells in higher plants and embryonic stem cells in animals, though some groups report the presence of adult pluripotent cells. Virally induced expression of four transcription factors Oct4, Sox2, c-Myc, and Klf4 (Yamanaka factors) is sufficient to create pluripotent (iPS) cells from adult fibroblasts. A multipotent cell is one that can differentiate into multiple different, but closely related cell types. Oligopotent cells are more restricted than multipotent, but can still differentiate into a few closely related cell types. Finally, unipotent cells can differentiate into only one cell type, but are capable of self-renewal. In cytopathology, the level of cellular differentiation is used as a measure of cancer progression. "Grade" is a marker of how differentiated a cell in a tumor is.
Before the 1921 destruction of Tulsa’s Greenwood District, Black residents had created a remarkable center of business and community life. The district included stores, professional offices, entertainment venues and homes owned by Black citizens. Understanding Greenwood means learning what was built—not only what was burned.
MORE →Madam C.J. Walker
