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Movements, leaders, victories and the continuing fight for equality.
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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.
In 1968 Shirley Chisholm became the first Black woman elected to the United States Congress. In 1972 she launched a campaign for the Democratic presidential nomination, breaking another political barrier.
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
Hes Family BHLH Transcription Factor 4 (HES4) is a protein encoded by a gene of the same name located on chromosome 1 in humans.[3] It does not currently have a known mouse ortholog.
HES4 plays a major role in key developmental processes, particularly in the immune system and bone formation. As a member of the basic helix-loop-helix (bHLH) family of transcription factors, HES4 plays a crucial role in T-cell development by responding to Notch1 signaling, which is vital for guiding hematopoietic progenitor cells toward becoming T-cells.[4]
Additionally, HES4 has emerged as a significant factor in the context of osteosarcoma (OS), a type of bone cancer, where its expression correlates with aggressive tumor behavior and poor patient prognosis.[5]
HES4 is a polypeptide chain consisting of 221 amino acids with a molecular weight of 23,523 Da.[6]
The secondary structure of the completed HES4 protein features a structural motif known as the basic helix-loop-helix (bHLH).[7] This motif is characterized by two alpha helices connected by a loop, which allows for a compact and flexible structure.[8]
The bHLH domain plays a critical role in DNA binding and protein–protein interactions, making it significant in various biological processes, particularly in the regulation of gene expression.[8] In HES4, the basic region of the motif typically contains positively charged amino acids that facilitate binding to specific DNA sequences, often in the context of transcriptional regulation.
HES4 plays an important role in the development of T-cells, which are a type of white blood cell that are a crucial part of the mammalian immune system. The process of T-cell development starts when a signaling pathway called Notch1 is activated in certain blood precursor cells, known as hematopoietic progenitor cells.
Notch1 activation is crucial for initiating T-cell development while suppressing differentiation into other lineages. While the functions of these genes are well understood in mice, the absence of a mouse ortholog for HES4 has made its role in humans less clear.
When Notch1 is activated, it acts like a switch that encourages these cells to become T-cells instead of other types of blood cells, such as those involved in the immune response or red blood cell formation. HES4 is one of the genes that responds to this activation, helping to guide the cells along the T-cell development path.
Research has shown that HES4 works alongside another gene called HES1. While both genes help suppress the development of other cell types, they do so in different ways. HES1 primarily keeps the cells in a resting state, allowing them to maintain their potential to become T-cells. In contrast, HES4 also supports the early stages of T-cell development but does not prevent the formation of B-cells, another important type of immune cell.[4]
Together, HES4 and HES1 ensure that as blood precursor cells receive the Notch1 signal, so that they successfully start their journey to becoming T-cells.
Because T-cells play an important role in constantly scrutinizing and destroying tumor cells,[9] and HES4 is important for the development of T-cells in humans, it has been hypothesised to be an oncogene and has been investigated using human cell lines and mice.
The clinical significance of HES4 in osteosarcoma (OS) is highlighted by its potential as a prognostic biomarker.
Studies using human OS cell lines both in vitro and injecting them into live mice in vivo have confirmed that overexpressing HES4 leads to larger and more aggressive tumors, with a greater tendency to spread to other parts of the body.[5]
Interestingly, while overexpressing HES4 promotes aggressive tumor behavior by inhibiting the normal bone cell differentiation process, another Notch1 target gene, HES1, has opposing effects, where overexpression has a preventative effect on tumor growth.[5]
Source: Wikipedia. Article content is retrieved live through the MediaWiki API.
Hes Family BHLH Transcription Factor 4 (HES4) is a protein encoded by a gene of the same name located on chromosome 1 in humans. It does not currently have a known mouse ortholog. HES4 plays a major role in key developmental processes, particularly in the immune system and bone formation. As a member of the basic helix-loop-helix (bHLH) family of transcription factors, HES4 plays a crucial role in T-cell development by responding to Notch1 signaling, which is vital for guiding hematopoietic progenitor cells toward becoming T-cells. Additionally, HES4 has emerged as a significant factor in the context of osteosarcoma (OS), a type of bone cancer, where its expression correlates with aggressive tumor behavior and poor patient prognosis.
A basic helix–loop–helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. "Basic" refers to the basic amino acid residues in the motif, which enable the protein to bind DNA. bHLH transcription factors are often important in development or cell activity. For one, BMAL1-Clock (also called ARNTL) is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism.
Leucine-rich repeats and IQ motif containing 1 is a protein that in humans is encoded by the LRRIQ1 gene. The protein is likely a nuclear encoding mitochondrial protein and is found in all Metazoans.
Nirogacestat, sold under the brand name Ogsiveo, is an anti-cancer medication used for the treatment of desmoid tumors. It is a selective gamma secretase inhibitor that is taken by mouth. Nirogacestat was approved for medical use in the United States in November 2023. It is the first medication approved by the US Food and Drug Administration (FDA) for the treatment of desmoid tumors. The FDA considers it to be a first-in-class medication.
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 →Shirley Chisholm, elected in 1968.
