BIOL 265 Lecture Notes - Lecture 2: Large Hadron Collider

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coralcrow517

14 Jan 2018

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Related Questions

- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 1.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 2.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 3.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 4.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 5.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 6.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 7.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 8.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 9.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 10.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 11.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 12.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 13.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 14.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 15.
- A. B. C. D. E. F. G. H. I. J. K. L. M. N. O. P.	Step 16.

A.	Don appropriate personal protective equipment (PPE).
B.	Aseptically transfer 1 mL from dilution tube 2 to dilution tube 3 and mix well. This is a 10^-5 cumulative dilution.
C.	Aseptically transfer 1.0 mL from dilution tube 4 to dilution tube 5 and mix well. This is a 10^-7 cumulative dilution.
D.	Aseptically transfer 0.1 mL from dilution tube 1 to dilution tube 2 and mix well. The cumulative dilution of the culture is 10^-4.
E.	Allow the inocula to soak into the plates before proceeding.
F.	Aseptically transfer 0.1 mL from dilution tube 2 to plate A₁. Using the spread plate technique, disperse the sample evenly over the entire surface of the agar.
G.	Aseptically transfer 1 mL from dilution tube 3 to dilution tube 4 and mix well. This is a 10^-6 cumulative dilution.
H.	Obtain eight plates, organize them int four pairs and label them A₁, A₂, B₁, B₂, etc.
I.	Keep accurate records in your lab notebook. Clean up the lab benches, doff PPE, and wash hands.
J.	Repeate the procedure with plate A₂ and label both plates "10^-5mL of original sample," or simply "10^-5" Notice that transferring 0.1 mL counts as a dilution!! The tube was a 10^-4 dilution, but the plate is a 10^-5 dilution!!
K.	Invert the plates so they are "agar up" to prevent condensation from ruining the plates.
L.	Repeat the aseptic transfer, spread plate technique, and label schematic for dilutions tubes 3, 4, and 5, and plates B, C, and D.
M.	Incubate the plates at 35â for 24 to 48 hours.
N.	Obtain five dilution tubes and label them 1â5, respectively. Make sure they remain covered until needed.
O.	Aseptically add 9.9 mL sterile water to dilution tubes 1 & 2. Cover when finished. Aseptically add 9.0 mL sterile water to dilution tubes 3, 4, and 5. Cover when finished.
P.	Mix the broth culture an aseptically transfer 0.1 mL to dilution tube 1. Mix dilution tube 1 well. This is a 10^-2 dilution

Compute the Person-Years of smoking exposure using the tablebelow. (Hint: add the years at risk of throat cancer (TC) â seeexamples).
Once they develop TC they are no longer at risk and their yearsin the study canât be counted.
Add each personâs years of exposure in the right column andenter the value in the box next to âTotal P-Y at Risk of ThroatCancerâ.
Then count the P-Y at risk for the Current/Former Smokers(exposed) and the P-Y at risk for the Never-Smokers (notexposed)
Using the Person-Years for each exposure group as thedenominator and the number of TC recorded for each exposure group;compute the Incidence Density for TC risk in current/former smokers(exposed) (ID_E) & compute the incidence density forTC risk in never smokers (not exposed) (ID_NE).
The compute the Incidence Density Ratio (also call RR), dividethe ID_Eby the ID_NE. This value is interpretedthe same as the Relative Risk.

		Years in the Study at Risk of Developing ThroatCancer								Years at Risk
Person	Smoker	1	2	3	4	5	6	7	8	Years at Risk
A	Yes	at risk	at risk	TC	No longer at risk of throat cancer					2
B	No	at risk	at risk	at risk	at risk	at risk	at risk	at risk	at risk	8
C	No
D	Yes						TC
E	Yes				TC
F	No
G	No					TC
H	No								TC
I	Yes		TC
J	Yes							TC
	Total P-Y at Risk of Throat Cancer

Sum the Person-Years of Exposure for each exposure group? (1point)

Former/Current Smoker (1/2 point)

Never Smoker(1/2 point)

How many of the exposed & not exposed participantsdeveloped throat cancer (1 point)?

Former/Current Smoker (1/2point):

Never Smoker(1/2point):

What is the Incidence Density for the exposed (ID_E)and non-exposed (ID_NE) groups? (1 point)

Former/Current Smoker (1/2point):

Never Smoker (1/2 point):

Compute the Incidence Density Ratio (IDR). Is the IDRprotective or hazardous? (1 point).

10. Using the interpretation for Relative Risk onpage 120 of your text, interpret the meaning of the IncidenceDensity Ratio (1 pt):

rubyjellyfish692

Enzyme Dysfunction in Disease (30 pts)

Protein kinases are key regulators of cellular physiology and, consequently, their dysfunction is associated with many diseases. Conversely, mutations and other defects sometimes help to illuminate gene function. Continuing with the exploration of the PI3K/AKT pathway, this exercise will seek to illuminate the role of certain residues and motifs in molecular functioning of AKT.

(1) Diseases associated with AKT1 mutations were identified in the first exercise. Following the same procedure and PUBMED searches, identify diseases associated mutations of AKT2 and AKT3 (some relevant papers are provided below).

(2) Through literature search or the references below, generate a table of disease-associated mutations of the above genes.

(4) Generate a hypothesis on the role of the PI3K/Akt in cancer or any other disease.

(5) Make predictions based on experiments that can be conducted in cell lines.

(4) Conduct sequence alignments of these proteins by selecting homologues from divergent species and identify the most highly conserved residues and motifs.

(5) Download the structure of AKT with and without ligands from the PDB and propose the consequences of the above mutations in protein function.

(6) Propose some experiments to test the predictions.

(7) Highlight three of the most highly conserved motifs on the protein structure and comment on their possible role in AKT function.

1. Revival of the abandoned therapeutic wortmannin by nanoparticle drug delivery.

Karve S, Werner ME, Sukumar R, Cummings ND, Copp JA, Wang EC, Li C, Sethi M, Chen RC, Pacold ME, Wang AZ. Proc Natl Acad Sci U S A. 2012 May 22;109(21):8230-5. doi: 10.1073/pnas.1120508109. Epub 2012 Apr 30. PMID: 22547809 Free PMC Article

2. Phase I clinical, pharmacokinetic, and pharmacodynamic study of the Akt-inhibitor triciribine phosphate monohydrate in patients with advanced hematologic malignancies.

Sampath D, Malik A, Plunkett W, Nowak B, Williams B, Burton M, Verstovsek S, Faderl S, Garcia-Manero G, List AF, Sebti S, Kantarjian HM, Ravandi F, Lancet JE. Leuk Res. 2013 Nov;37(11):1461-7. doi: 10.1016/j.leukres.2013.07.034. Epub 2013 Aug 6.PMID: 23993427

The Mechanism of ATP-Dependent Allosteric Protection of Akt Kinase Phosphorylation.

Lu S, Deng R, Jiang H, Song H, Li S, Shen Q, Huang W, Nussinov R, Yu J, Zhang J.

Structure. 2015 Sep 1;23(9):1725-34. doi: 10.1016/j.str.2015.06.027. Epub 2015 Aug 6.

PMID:26256536

Similar articlesRemove from clipboard

Select item 262867482.

Alternative activation mechanisms of Protein Kinase B trigger distinct downstream signaling responses.

Balzano D, Fawal MA, Velazquez JV, Santiveri CM, Yang J, Pastor J, Campos-Olivas R, Djouder N, Lietha D.

J Biol Chem. 2015 Aug 18. pii: jbc.M115.651570. [Epub ahead of print]

PMID:26286748

Free Article

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Select item 260530933.

Mutant AKT1-E17K is oncogenic in lung epithelial cells.

De Marco C, Malanga D, Rinaldo N, De Vita F, Scrima M, Lovisa S, Fabris L, Carriero MV, Franco R, Rizzuto A, Baldassarre G, Viglietto G.

Oncotarget. 2015 May 25. [Epub ahead of print]

PMID:

26053093

Free Article

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Select item 242856834.

Activating AKT2 mutation: hypoinsulinemichypoketotic hypoglycemia.

Arya VB, Flanagan SE, Schober E, Rami-Merhar B, Ellard S, Hussain K.

J ClinEndocrinolMetab. 2014 Feb;99(2):391-4. doi: 10.1210/jc.2013-3228. Epub 2013 Nov 27.

PMID:

24285683

Similar articlesRemove from clipboard

Select item 235242935.

AGC protein kinases: from structural mechanism of regulation to allosteric drug development for the treatment of human diseases.

Arencibia JM, Pastor-Flores D, Bauer AF, Schulze JO, Biondi RM.

BiochimBiophysActa. 2013 Jul;1834(7):1302-21. doi: 10.1016/j.bbapap.2013.03.010. Epub 2013 Mar 21. Review.

PMID:

23524293

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Select item 220316986.

Resistance of Akt kinases to dephosphorylation through ATP-dependent conformational plasticity.

Chan TO, Zhang J, Rodeck U, Pascal JM, Armen RS, Spring M, Dumitru CD, Myers V, Li X, Cheung JY, Feldman AM.

Proc Natl AcadSci U S A. 2011 Nov 15;108(46):E1120-7. doi: 10.1073/pnas.1109879108. Epub 2011 Oct 26. PMID: 22031698

The nuts and bolts of AGC protein kinases. Pearce LR, Komander D, Alessi DR. Nat Rev Mol Cell Biol. 2010 Jan;11(1):9-22. doi: 10.1038/nrm2822. Review.

PMID: 20027184

Somatic mutations affect key pathways in lung adenocarcinoma.

Ding L, Getz G, Wheeler DA, Mardis ER, McLellan MD, Cibulskis K, Sougnez C, Greulich H, Muzny DM, Morgan MB, Fulton L, Fulton RS, Zhang Q, Wendl MC, Lawrence MS, Larson DE, Chen K, Dooling DJ, Sabo A, Hawes AC, Shen H, Jhangiani SN, Lewis LR, Hall O, Zhu Y, Mathew T, Ren Y, Yao J, Scherer SE, Clerc K, Metcalf GA, Ng B, Milosavljevic A, Gonzalez-Garay ML, Osborne JR, Meyer R, Shi X, Tang Y, Koboldt DC, Lin L, Abbott R, Miner TL, Pohl C, Fewell G, Haipek C, Schmidt H, Dunford-Shore BH, Kraja A, Crosby SD, Sawyer CS, Vickery T, Sander S, Robinson J, Winckler W, Baldwin J, Chirieac LR, Dutt A, Fennell T, Hanna M, Johnson BE, Onofrio RC, Thomas RK, Tonon G, Weir BA, Zhao X, Ziaugra L, Zody MC, Giordano T, Orringer MB, Roth JA, Spitz MR, Wistuba II, Ozenberger B, Good PJ, Chang AC, Beer DG, Watson MA, Ladanyi M, Broderick S, Yoshizawa A, Travis WD, Pao W, Province MA, Weinstock GM, Varmus HE, Gabriel SB, Lander ES, Gibbs RA, Meyerson M, Wilson RK.

Nature. 2008 Oct 23;455(7216):1069-75. doi: 10.1038/nature07423. PMID: 18948947

Mechanism for activation of the growth factor-activated AGC kinases by turn motif phosphorylation. Hauge C, Antal TL, Hirschberg D, Doehn U, Thorup K, Idrissova L, Hansen K, Jensen ON, JÃ¸rgensen TJ, Biondi RM, FrÃ¶din M. EMBO J. 2007 May 2;26(9):2251-61. Epub 2007 Apr 19. PMID: 17446865

Structure, regulation and function of PKB/AKT--a major therapeutic target.

Hanada M, Feng J, Hemmings BA.

BiochimBiophysActa. 2004 Mar 11;1697(1-2):3-16. Review.

PMID: 15023346

AKT/PKB and other D3 phosphoinositide-regulated kinases: kinase activation by phosphoinositide-dependent phosphorylation.

Chan TO, Rittenhouse SE, Tsichlis PN Annu Rev Biochem. 1999; 68():965-1014.

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BIOL 265 Lecture Notes - Lecture 2: Large Hadron Collider

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