This is what I waited to read?

Pretty sure the vast majority of Tumblr has never heard of the Vampire Huntress Legend saga by the late L.A. Banks. But for those that have and liked it, DON’T READ THE GRAPHIC NOVEL. I picked up the only novel of the Neteru Academy arc, but I felt like there were some parts of the story that got lost in the time lapse. Why was I so foolish as to think I’d get more of an explaination from the graphic novels?

They’re short. I used to be an avid manga reader and even read a few graphic novels that accompanied textual novels, so I know the average length I can expect one to be. All four books could have fit into one. There is a tablespoon’s worth of a plot, which probably explains the length. But what plot there is is jerky, uninformative, and nothing like what you’d expect from the series. If you’re going to call it a cliffhanger, at least give enough information to capture your audience’s interest.

My biggest issue, and the one that made me cringe throughout all four books, is the art. The artists change from book to book and it’s apparent that none of them read the character descriptions (or just saw fit to ignore them). Most of the darker characters are whitewashed all to hell, their dreads magically turn into relaxed hair half the time and their expressions could belong to one reading the newspaper. This is a series about spirituality, action, and demon hunting. You’d think the faces of the Neteru team would reflect more than boredom upon hearing the deaths of dozens of children.

My personal opinion? Don’t waste your time.

Oncogenes and tumour suppressors are mutation targets promoting the onset and maintenance of cancer. Oncogenic mutations result in gain-of-function and deregulation of the function of the oncoprotein that they encode. Tumour suppressors act to run quality checking of DNA, keep cell cycle checkpoints, and shut down mitogenic signals; mutations in genes encoding tumour suppressors can lead to absence of these checks and give activated oncoproteins the chance to run riot in a cell. Co-incidence of mutations in oncogenes and tumour suppressor genes potentially leads to cancer.


Ras is a small G protein involved in a whole host of cellular functions. Mutation of Ras at a functional site can lead to a pleiotropic phenotype. Oncogenic Ras causes inappropriate signalling through its three pathways: MAPK, PI3K, and RalGEF. Signalling through the PI3K activates antiapoptotic Akt (PKB), which acts to promote cell survival. Signalling through RalGEF causes cell motility by formation of filopodia (Cdc42) and lamellipodia (Rac), which may be associated with metastasis. Signalling through MAPK actually causes the expression of some Ras signalling inhibitors (Sproutys, SPREDs, GAPs) which shuts down the signal in normal cells.

Myc is a transcription factor with more than 8000 transcription targets. Deregulated Myc leads to cell proliferation, but does not block apoptosis. Thus, it leads to a modest amount of growth before it is eradicated by apoptosis. Inhibition of apoptosis by antiapoptotic Bcl-xL is tumourigenic in cells expressing Myc highly. Additionally, Myc is thought to contribute to the tumour microenvironment, immune evasion, and inhibition of differentiation.

Ras and Myc work together by combining their abilities. Myc promotes cell proliferation and disfavours differentiation, and Ras inhibits apoptosis. The combination of the two means that cells are allowed to proliferate without triggering apoptosis. Ras actually activates Myc in normal cells - but in normal cells, activation is transient. Ras stabilises Myc by phosphorylation on S62 through MEK signalling, but also promotes its degradation by phosphorylation on T58 through PI3K signalling. The result is transient activation of Myc by Ras. Mutations which ultimately block phosphorylation at T58 will switch activation by Ras from a transient to a constitutive response.

Tumour suppressors

p53 is the so-called guardian of the genome. High Myc and oncogenic Ras cause stabilisation and activation of p53. p53 gets two bites at the cherry to combat the inheritance of damaged genomes: at the point of DNA damage, p53 arrests the cell until the DNA is repaired. p53 decides whether the cell enters senescence or apoptosis - its own state of post-translational modifications and the genomic context of its target genes (p53 is also a TF) on the genome in that particular cell both play a role in which way the scale tips. In this way, p53’s second bite of the cherry is the selection of apoptosis in cells whose DNA is damaged beyond repair.

Rb is the keeper of the G1/S checkpoint. Loss of both copies of the Rb gene leads to retinoblastoma. Familial retinoblastoma predisposes heterozygotes with a heightened risk of retinoblastoma by loss of heterozygosity - loss of their only functional copy. This can occur by mutation, but also by mitotic recombination, gene conversion, and nondisjunction. Cells null for Rb can still enter G0 phase, as p107 and p130 share some redundant functions with Rb.

NF1 displays the phenomenon of haploinsufficiency. Nf1-/- Schwann cells can be complemented for the wild-type by Nf1+/+ mast cells, but not Nf1+/- mast cells. The former gives the wild-type; the latter causes neurofibromas.

VHL suppresses the hypoxic response in normoxia by mediating the ubiquitin-associated degradation of HIF-1α in normoxia. Loss of VHL leads to a hypoxic response no matter the oxygen level.

Further reading:

  • Hanahan, D.; Weinberg, R.A. 2011. “Hallmarks of cancer: The next generation.” Cell 144:646-674.
  • Lowe, S.W.; Cepero, E.; Evan, G. 2004. “Intrinsic tumour suppression.” Nature 432:307-315.
  • Pylayeva-Gupta, Y.; Grabocka, E.; Bar-Sagi, D. 2011. “RAS oncogenes: Weaving a tumorigenic web.” Nature Reviews Cancer 11:761-774.
  • Soucek, L.; Evan, G.I. 2010. “The ups and downs of Myc biology.” Current Opinion in Genetics and Development 20:91-95.
  • Vousden, K.H.; Prives, C.; 2009. “Blinded by the light: The growing complexity of p53.” Cell 137:413-431.
  • Burkhart, D.L.; Sage, J. 2008. “Cellular mechanisms of tumour suppression by the retinoblastoma gene.” Nature Reviews Cancer 8:671-682.
Autosomal Dominant Diseases Mnemonic: HAT OF MAN POWER VL
  • H untington’s disease: CAG triplet, chorea, anticipation, delayed age of onset, alteration of gene expression due to hypermethilation of histones
  • H ereditary spherocitosis: membrane defect --> anykrin & spectrin
  • H ereditary Hemorragic Telangectasia (Osler-Weber-Rendu Sd): mucosal telangectasias, recurren epistaxis, skin decoloration, AVM, GI bleeding (hematochesia)
  • H ypertrophic Obstructive Cardiomyopathy: sudden <3 death, MC mutation, beta-myosin heavy chain
  • H ypokalemic Periodic Paralysis: episodes of muscle weakness, severe paralysis, channelopathy, ↓K+ serum (goes into muscle cells)
  • A chondroplasia: Fibroblast Growth Factor Receptor 3 gene (FGFR-3), chromosome 4
  • T uberous Sclerosis: T-S genes; TSC-1(hamartin), TSC-2(tuberin), chromosome 16. Kidney angiolipomas, <3 rhabdomyomas, tubers in brain (non-malignant), astrocytomas, seizures, developmental delay, MR, behavioral problems, hamartomas, skin abnormalities (shagreen patches, ashleaf spots, sebaceous adenomas, facial angiofibromas)
  • .
  • O steogenesis Imperfecta (except type VII): type 1 collagen
  • F amilial hypercholesterolemia: type IIa, LDL receptor deficiency, chromosome 19
  • F amilial Adenomatous Polyposis (FAP) & Peutz Jeghers Sd: APC gene, chromosome 5
  • .
  • M arfan Sd: defective fibrillin, chromosome 15
  • M yotonic Dystrophy: CTG triplet, anticipation. DMPK gene, abnormal expression of Myotonin Protein Kinase. Muscle loss, <3 arrythmia, testicular atrophy, frontal baldness, cataracts.
  • A cute Intermitent Porphyria: porphobillinogen deaminase deficiency, dark, port-wine urine, delayed age of onset.
  • N eurofibromatosis type I: NF1 gene, VonRecklinghausen, chromosome 17, sphenoid dysplasia, congenital pseudoarthrosis, scoliosis, meningiomas, gliomas, pheochromocytoma.
  • .
  • P olydactyly: ulnar, radial, central.
  • P olycystic Kidney Disease (ZD - adults): PCKD1 gene (85%) - chromosome 16; PCKD2 gene (15%) -chromosome 4; large, round cysts. Assoc. w/ cysts in liver, pancreas, berry aneurisms in circle of Willis, colonic diverticula, MVP.
  • O steopetrosis Type II – adult type: thick, dense bones (marble bones), osteoclast disfunction.
  • W aardenburg Sd: deafness, lateral displacement of inner canthi, hypertelorism, white patches of skin in ventral midline.
  • E hlers - Danlos Sd: it can be AR too. Collagen cross linking defect.
  • R etinoblastoma: Rb gene, chromosome 13
  • .
  • V on Hipel Lindau: VHL tumor suppresor gene, chromose 3, benign/malignant tumors (CNS), capillary hemangioblastomas, clear cell ca of kidney, pheocrhomocytomas, pancreactic NE tumors.
  • V on Willebrand Disease: vWF deficiency
  • L i Fraumeni Sd: p53 mutation, young age onset of malignancy, <45yo, family hx, cancer everywhere (breast, brain, leukemias, adrenal cortex)

Локомотив будет жить / Lokomotiv’s first VHL game LIVE on YouTube (by KHLofficialvideo)

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Von Hippel Lindau - USMLE Nuggets (by USMLESuccessAcademy)