Flashcards in Important discoveries Deck (26):
Hill et al (2016)
Certain gut bacteria are necessary for the pancreas to populate itself with a robust number of beta cells during development by releasing a protein called BefA that causes the beta cells to multiply.
Andersson et. al. (2012)
Screening small molecules that act on the adenosine signaling pathway found an adenosine agonist called NECA which is a potent enhancer of β cell regeneration in both zebrafish and mice.
Cohen et al (2001)
Selective deletion of leptin receptor in specific neurons leads to obesity in mice showing that the brain is a direct target for the weight-reducing and neuroendocrine effects of leptin.
Robins et al (2013)
α-tanycytes are self-renewing cells that form the critical component of a hypothalamic stem cell niche. Their proliferation is governed by local fibroblast growth factor signalling.
Nasif et al (2015)
The early expression/coexpression of Islet 1 (ISL1) in the developing hypothalamus is essential for hypothalamic Pomc expression and therefore normal adiposity in mice and zebrafish throughout the entire lifetime.
Scarlett et al (2016)
Administering rat and mice models of T2D with an intracerebroventricular injection of FGF1 initiates sustained diabetes remission, which does not cause weight loss or hypoglycemia.
Nusslein-Volhard and Weischaus (1980)
Mutagenesis screen in Drosophila and discovered patterning genes including Wg.
Clevers and Nusse (2014)
At the bottom of the intestinal crypt, paneth and stromal cells supply Wnt signalling to sustain the self-renewal of stem cells exclusively at the bottom. Cells moving upwards begin to differentiate.
Myant et al (2013)
After APC is lost, RAC1 uses ROS production and NF-κB activation a critical to cause expansion of the LGR5 intestinal stem cell, progenitor hyperproliferation, and transformation to initiate colorectal cancer.
Taipale et al (2000)
Many tumours are caused by mutations that activate the proto-oncogene Smoothened (SMO) or that inactivate the tumour suppressor Patched (PTCH), causing increase Hh signalling. Cyclopamine can block activation of the Hh response pathway and abnormal cell growth associated with both types of oncogenic mutation.
Davies et al (2002)
The RAS–RAF–MEK–ERK–MAP kinase pathway mediates cellular responses to growth signals. BRAF somatic missense mutations in kinase domain present in 66% of malignant melanomas and at lower frequency in a wide range of human cancers causing increased kinase activity.
Yang et al (2010)
PLX4702, a small-molecule inhibitor of BRAF(V600E) kinase activity potently inhibits proliferation and ERK kinase and ERK phosphorylation. In xenograft models of BRAF(V600E)-expressing melanoma, PLX4702 treatment caused partial or complete tumor regressions.
White et al (2011)
Neural crest progenitors from zebrafish transgenic embryos mitfa:BRAF(V600E) lacking p53 fail to terminally differentiate. DHODH-class Leflunomide exerts inhibits the transcriptional elongation of genes that are required for neural crest development and melanoma growth. DHODH inhibition led to a marked decrease in melanoma growth both in vitro and in mouse xenograft studies.
Ceol et al (2011)
Zebrafish melanoma model were used to test for genes on chromosome 1 that associate with BRAFV6003. They found SETDB1, an enzyme that methylates histone H3 on lysine 9 which accelerates melanoma formation by dysregulating HOX genes.
Wichterle et al (2002)
Relevant signaling factors can induce mouse embryonic stem (ES) cells to differentiate into spinal progenitor cells, and subsequently into motor neurons, through a pathway recapitulating that used in vivo.
Miles et al (2004)
MNs can be derived from transgenic mouse ES cell line where GFP is under control of Hb9 promoter. ES cells were exposed to RA and Shh to stimulate differentiation. Resultant motor neurons develop appropriate transmitter receptors, intrinsic properties for appropriate action potential firing and functional synapses with muscle fibers.
Grand Challenges in Mental Health
Aim to bring mental, neurological and substance use disorders to the forefront of global attention and scientific inquiry, identifying research priorities that, if addressed within the next decade, could lead to substantial improvements in the lives of people living with neuropsychiatric illnesses.
Eachus et al (2017)
Adult zebrafish homozygous mutant for disc1 show aberrant behavioural responses to stress. In disc1 mutant embryos neuronal differentiation is compromised in rx3-derived, ff1b+ and crh neurons. Altered crh levels fail to upregulate cortisol levels when under stress and do not modulate normal social behaviour.
Hall, Rosbash and Young (Nobel Prize 2017)
Identified the protein components of the circadian clock machinery, exposing the mechanism governing the self-sustaining clockwork inside the cell mostly determined by an inhibitory feedback loop of the PER protein.
Landgraf et al (2016)
Disrupting suprachiasmatic nucleus circadian rhythms is sufficient to cause helplessness, behavioral despair, and anxiety-like behavior in mice, establishing SCN-Bmal1-KD mice as a new animal model of depression.
Wulff et al (2012)
Significant sleep/circadian disruption occurred in schizophrenic participants. Half showed severe circadian misalignment in sleep-wake and melatonin cycles, and the other half showed patterns from excessive sleep to highly irregular and fragmented sleep epochs but with normally timed melatonin production.
Clancy et al (2001)
Drosophila gene chico encodes an insulin receptor substrate that functions in an insulin/insulin-like growth factor signaling pathway. Mutation of chico extends fruit fly median life-span by up to 48% in homozygotes and 36% in heterozygotes.
Tsuda et al (2010)
Insulin-degrading enzyme antagonizes insulin-dependent tissue growth and Abeta-induced neurotoxicity in Drosophila. IDE is implicated in the pathogenesis of type 2 diabetes mellitus and Alzheimer's disease.
Moore et al. (1998)
Using an inebriometer to measure ethanol-induced loss of control, cheapdate was identified, a mutant with enhanced sensitivity to ethanol which can be reversed by treatment with agents that increase cAMP levels or PKA activity. This shows that cAMP transduction pathway is involved.
Kang et al (2009)
By hitting cancer cells with chemotherapy at a time when their ability to repair themselves is minimal i.e. at night, you should be able to maximize effectiveness and minimize side effects of treatment.