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MY'STORY

The MOVE Fire

This is a personal recollection on the Move fire on May 13, 1985 Philadelphia police fired thousands of rounds at the MOVE house, city officials approved dropping an explosive device on the roof, the resulting fire was allowed to burn, 11 people—including five children—died, and 61 homes were destroyed. Philadelphia City Council later called it a “brutal attack carried out by the City of Philadelphia on its own citizens” and acknowledged that no individual faced criminal consequences for the bombing. One timeline correction worth preserving for the BHP record: the major previous MOVE-police confrontation was August 8, 1978, about seven years before the bombing, not a year or two earlier. Officer James Ramp was killed, other police and firefighters were wounded, nine MOVE members were later convicted, and television cameras recorded police beating Delbert Africa during his arrest. The 1985 MOVE Commission later specifically criticized city planners for failing to adequately use lessons from that 1978 confrontation. And that actually strengthens the point you’re making: 1985 did not happen without precedent or institutional memory. There had already been a deadly confrontation with MOVE, years of conflict, negotiations and police involvement before Osage Avenue.

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BLACK FACTS
The Truths They Never Taught You...

Ruler of the Mali Empire in the 14th century

Mansa Musa was the ruler of the Mali Empire in West Africa. Details recorded here should be sourced; unknown information is left blank.

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BHP gathered finds from its connected research sources. Showing the 4 strongest Black History matches.
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Wikipedia

Deoxygedunin

Deoxygedunin
Clinical data
Other names14,15-Deoxygedunin
ATC code
  • None
Identifiers
  • (1R,6R,7R,10R,11R,16R,18R)‐6‐(Furan‐3‐yl)‐1,7,11,15,15‐pentamethyl‐4,14‐dioxo‐5‐oxatetracyclo[8.8.0.02,7.011,16]octadeca‐2,12‐dien‐18‐yl acetate
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC28H34O6
Molar mass466.574 g·mol−1
3D model (JSmol)
  • CC(=O)OC1CC2C(C(=O)C=CC2(C3C1(C4=CC(=O)OC(C4(CC3)C)C5=COC=C5)C)C)(C)C
  • InChI=1S/C28H34O6/c1-16(29)33-22-13-19-25(2,3)21(30)8-11-26(19,4)18-7-10-27(5)20(28(18,22)6)14-23(31)34-24(27)17-9-12-32-15-17/h8-9,11-12,14-15,18-19,22,24H,7,10,13H2,1-6H3
  • Key:VOUDTVRGPAGHGA-UHFFFAOYSA-N

Deoxygedunin, or 14,15-deoxygedunin, is a tetranortriterpenoid isolated from the Indian neem tree[1][2] a plant that has been in traditional Indian medicine since ancient times as a remedy for various ailments.[3]

Pharmacology

[edit]

Deoxygedunin has been found to act as a potent, selective, small-molecule agonist of TrkB, the main receptor of brain-derived neurotrophic factor (BDNF).[1][2] It produces TrkB-dependent neurotrophic and neuroprotective effects in mice and enhances learning processes.[1][4] In addition, deoxygedunin evokes rapid TrkB-dependent antidepressant-like effects in the forced swim test, an animal model of depression, similarly to 7,8-dihydroxyflavone (7,8-DHF) and ketamine, and notably with a greater potency than 7,8-DHF.[1][2][5] The compound was discovered by the same group that identified 7,8-DHF and N-acetylserotonin as TrkB agonists.[1]

Research

[edit]

With intraperitoneal injection to mice, deoxygedunin crosses the blood-brain-barrier into the central nervous system and possesses a long duration of action, with onset of action at 2 hours post-administration and peaking between 4–8 hours.[1] Relative to 7,8-DHF, deoxygedunin has weaker binding affinity for TrkB (Kd = 1.4 μM).[1][2] However, it is more potent than 7,8-DHF in vivo with intraperitoneal injection in multiple assays.[1] Deoxygedunin has also been found to be orally and topically active.[1][4] The compound, in contrast to 7,8-DHF, has poor water solubility,[1] and hence its bioavailability, especially oral, may be suboptimal.[6] The researchers who discovered deoxygedunin expressed that they were attempting to find analogues with improved water solubility that retained the biological activity of deoxygedunin, but, as of 2016, there appear to have been no subsequent reports on this effort since the original paper (2010) was published.[1] They also stated in the paper that 7,8-DHF has a simpler chemical structure and that the flavonoids were easier to modify for improved biological effects than the gedunins.[1]

Similarly to gedunin, a closely structurally related compound also found in Azadirachta indica, deoxygedunin has additionally been found to activate HSF1 and induce Hsp70, and was observed to possess neuroprotective effects in a model of Huntington's disease.[7]

See also

[edit]

References

[edit]
  1. ^ a b c d e f g h i j k l Jang SW, Liu X, Chan CB, France SA, Sayeed I, Tang W, et al. (July 2010). "Deoxygedunin, a natural product with potent neurotrophic activity in mice". PLOS ONE. 5 (7) e11528. Bibcode:2010PLoSO...511528J. doi:10.1371/journal.pone.0011528. PMC 2903477. PMID 20644624.
  2. ^ a b c d Nordvall G, Forsell P (24 September 2014). "Stimulating neurotrophin receptors in the treatment of neurodegenerative disorders.". In Robichaud AJ (ed.). Annual Reports in Medicinal Chemistry. Elsevier Science. pp. 69–. ISBN 978-0-12-800372-5.
  3. ^ Vaibhav K, Shrivastava P, Khan A, Javed H, Tabassum R, Ahmed ME, et al. (August 2013). "Azadirachta indica mitigates behavioral impairments, oxidative damage, histological alterations and apoptosis in focal cerebral ischemia-reperfusion model of rats". Neurological Sciences. 34 (8): 1321–1330. doi:10.1007/s10072-012-1238-z. PMID 23187787. S2CID 2022138.
  4. ^ a b English AW, Liu K, Nicolini JM, Mulligan AM, Ye K (October 2013). "Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves". Proceedings of the National Academy of Sciences of the United States of America. 110 (40): 16217–16222. Bibcode:2013PNAS..11016217E. doi:10.1073/pnas.1303646110. PMC 3791704. PMID 24043773.
  5. ^ Zhang JC, Yao W, Dong C, Yang C, Ren Q, Ma M, et al. (December 2015). "Comparison of ketamine, 7,8-dihydroxyflavone, and ANA-12 antidepressant effects in the social defeat stress model of depression". Psychopharmacology. 232 (23): 4325–4335. doi:10.1007/s00213-015-4062-3. PMID 26337614. S2CID 15076700.
  6. ^ Kakran M, Li L, Müller RH (July–August 2012). "Overcoming the Challenge of Poor Drug Solubility" (PDF). Pharmaceutical Engineering. Vol. 32, no. 4. International Society for Pharmaceutical Engineering.[dead link]
  7. ^ Dinkova-Kostova AT, Zhang Y, Naidu SD, Kostov RV, Pheely A, Calabrese V (3 December 2013). "Sulfhydryl-reactive phytochemicals as dual activators of transcription factors NRF2 and HSF1.". In Gang D (ed.). 50 Years of Phytochemistry Research. Vol. 43. Springer Science & Business Media. pp. 103–. ISBN 978-3-319-00581-2.

Source: Wikipedia. Article content is retrieved live through the MediaWiki API.

Wikipedia

Deoxygedunin

Deoxygedunin, or 14,15-deoxygedunin, is a tetranortriterpenoid isolated from the Indian neem tree a plant that has been in traditional Indian medicine since ancient times as a remedy for various ailments.

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Wikipedia

Insulin

Insulin ( ; from Latin insula 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the insulin (INS) gene. It is the main anabolic hormone of the body. It regulates the metabolism of carbohydrates, fats, and protein by promoting the absorption of glucose from the blood into cells of the liver, fat, and skeletal muscles. In these tissues the absorbed glucose is converted into either glycogen, via glycogenesis, or fats (triglycerides), via lipogenesis; in the liver, glucose is converted into both. Glucose production and secretion by the liver are strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is thus an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules in the cells. Low insulin in the blood has the opposite effect, promoting widespread catabolism, especially of reserve body fat. Beta cells are sensitive to blood sugar levels so that they secrete insulin into the blood in response to high level of glucose, and inhibit secretion of insulin when glucose levels are low. Insulin enhances glucose uptake and metabolism in the cells, thereby reducing blood sugar. Neighboring alpha cells, taking their cue from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon increases blood glucose by stimulating glycogenolysis and gluconeogenesis in the liver. The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism of glucose homeostasis. Decreased or absent insulin activity results in diabetes, a condition of high blood sugar level (hyperglycaemia). There are two types of the disease. In type 1 diabetes, the beta cells are destroyed by an autoimmune reaction so that insulin can no longer be synthesized or be secreted into the blood. In type 2 diabetes, the destruction of beta cells is less pronounced than in type 1, and is not due to an autoimmune process. Instead, there is an accumulation of amyloid in the pancreatic islets, which likely disrupts their anatomy and physiology. The pathogenesis of type 2 diabetes is not well understood but reduced population of islet beta-cells, reduced secretory function of islet beta-cells that survive, and peripheral tissue insulin resistance are known to be involved. Type 2 diabetes is characterized by increased glucagon secretion which is unaffected by, and unresponsive to the concentration of blood glucose. However, insulin is still secreted into the blood in response to the blood glucose. As a result, glucose accumulates in the blood. The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a heterodimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin's structure varies slightly between species of animals. Insulin from non-human animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies. Insulin was the first peptide hormone discovered. Frederick Banting and Charles Best, working in the laboratory of John Macleod at the University of Toronto, were the first to isolate insulin from dog pancreas in 1921. Frederick Sanger sequenced the amino acid structure in 1951, which made insulin the first protein to be fully sequenced. The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin in 1969. Insulin is also the first protein to be chemically synthesised and produced by DNA recombinant technology. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

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Wikipedia

Testosterone

Testosterone is the primary male sex hormone and androgen in males. In humans, testosterone drives the development of male reproductive tissues such as testicles and prostate, as well as promoting secondary sexual characteristics such as increased muscle and bone mass, and the growth of body hair. It is associated with increased aggression, sex drive, dominance, courtship display, and a wide range of behavioral characteristics. In addition, testosterone in both sexes is involved in health and well-being, where it has a significant effect on overall mood, cognition, social and sexual behavior, metabolism and energy output, the cardiovascular system, and in the prevention of osteoporosis. Insufficient levels of testosterone in men may lead to abnormalities including frailty, accumulation of adipose fat tissue within the body, anxiety and depression, sexual performance deficits, and bone loss. Excessive levels of testosterone in men may be associated with hyperandrogenism, higher risk of heart failure, increased mortality in men with prostate cancer, and male pattern baldness. Testosterone is a steroid hormone from the androstane class containing a ketone and a hydroxyl group at positions three and seventeen respectively. It is biosynthesized in several steps from cholesterol and is converted in the liver to inactive metabolites. It exerts its action through binding to and activation of the androgen receptor. In humans and most other vertebrates, testosterone is secreted primarily by the testicles of males and, to a lesser extent, the ovaries of females. On average, in adult males, levels of testosterone are about seven to eight times as great as in adult females. As the metabolism of testosterone in males is more pronounced, the daily production is about 20 times greater in men. Females are also more sensitive to the hormone. In addition to its role as a natural hormone, testosterone is used as a medication to treat hypogonadism and breast cancer. Since testosterone levels decrease as men age, testosterone is sometimes used in older men to counteract this deficiency. It is also used illicitly to enhance physique and performance, for instance in athletes. The World Anti-Doping Agency lists it as S1 Anabolic agent substance "prohibited at all times".

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Wikipedia

Erythropoietin

Erythropoietin (; EPO), also known as erythropoetin, haematopoietin, or haemopoietin, is a glycoprotein cytokine secreted mainly by the kidneys in response to cellular hypoxia; it stimulates red blood cell production (erythropoiesis) in the bone marrow. Low levels of EPO (around 10 mU/mL) are constantly secreted in sufficient quantities to compensate for normal red blood cell turnover. Common causes of cellular hypoxia resulting in elevated levels of EPO (up to 10 000 mU/mL) include any anemia, and hypoxemia due to chronic lung disease. Erythropoietin is largely synthesized in the deep renal cortex by peritubular interstitial fibroblast-like cells, namely located primarily in close association with the peritubular capillaries and proximal convoluted tubule; it is also produced in perisinusoidal cells in the liver. Liver production predominates in the fetal and perinatal period; renal production predominates in adulthood. It is homologous with thrombopoietin. Exogenous erythropoietin, recombinant human erythropoietin (rhEPO), is produced by recombinant DNA technology in cell culture and are collectively called erythropoiesis-stimulating agents (ESA): two examples are epoetin alfa and epoetin beta. ESAs are used in the treatment of anemia in chronic kidney disease, anemia in myelodysplasia, and in anemia from cancer chemotherapy. Risks of therapy include death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence. Risk increases when EPO treatment raises hemoglobin levels over 11 g/dL to 12 g/dL: this is to be avoided. rhEPO has been used illicitly as a performance-enhancing drug. It can often be detected in blood, due to slight differences from the endogenous protein; for example, in features of posttranslational modification.

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TOPIC OF THE DAY

Greenwood / Black Wall Street

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.

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TRIVIA QUESTION OF THE DAY

Which Supreme Court case ruled state-sponsored public-school segregation unconstitutional?

Brown v. Board of Education in 1954.