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From Proteopedia
The DNA-binding domain of the tumor suppressor p53 is inactivated by mutation in approximately 50% of human cancers. We have solved high-resolution crystal structures of several oncogenic mutants to investigate the structural basis of inactivation and provide information for designing drugs that may rescue inactivated mutants. We found a variety of structural consequences upon mutation: (i) the removal of an essential contact with DNA, (ii) creation of large, water-accessible crevices or hydrophobic internal cavities with no other structural changes but with a large loss of thermodynamic stability, (iii) distortion of the DNA-binding surface, and (iv) alterations to surfaces not directly involved in DNA binding but involved in domain-domain interactions on binding as a tetramer. These findings explain differences in functional properties and associated phenotypes (e.g., temperature sensitivity). Some mutants have the potential of being rescued by a generic stabilizing drug. In addition, a mutation-induced crevice is a potential target site for a mutant-selective stabilizing drug.
Structural basis for understanding oncogenic p53 mutations and designing rescue drugs., Joerger AC, Ang HC, Fersht AR, Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:17015838
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
[P53_HUMAN] Note=TP53 is found in increased amounts in a wide variety of transformed cells. TP53 is frequently mutated or inactivated in about 60% of cancers. TP53 defects are found in Barrett metaplasia a condition in which the normally stratified squamous epithelium of the lower esophagus is replaced by a metaplastic columnar epithelium. The condition develops as a complication in approximately 10% of patients with chronic gastroesophageal reflux disease and predisposes to the development of esophageal adenocarcinoma. Defects in TP53 are a cause of esophageal cancer (ESCR) [MIM:133239]. Defects in TP53 are a cause of Li-Fraumeni syndrome (LFS) [MIM:151623]. LFS is an autosomal dominant familial cancer syndrome that in its classic form is defined by the existence of a proband affected by a sarcoma before 45 years with a first degree relative affected by any tumor before 45 years and another first degree relative with any tumor before 45 years or a sarcoma at any age. Other clinical definitions for LFS have been proposed (PubMed:8118819 and PubMed:8718514) and called Li-Fraumeni like syndrome (LFL). In these families affected relatives develop a diverse set of malignancies at unusually early ages. Four types of cancers account for 80% of tumors occurring in TP53 germline mutation carriers: breast cancers, soft tissue and bone sarcomas, brain tumors (astrocytomas) and adrenocortical carcinomas. Less frequent tumors include choroid plexus carcinoma or papilloma before the age of 15, rhabdomyosarcoma before the age of 5, leukemia, Wilms tumor, malignant phyllodes tumor, colorectal and gastric cancers.[1][2][3][4][5][6][7][8][9][10] Defects in TP53 are involved in head and neck squamous cell carcinomas (HNSCC) [MIM:275355]; also known as squamous cell carcinoma of the head and neck. Defects in TP53 are a cause of lung cancer (LNCR) [MIM:211980]. LNCR is a common malignancy affecting tissues of the lung. The most common form of lung cancer is non-small cell lung cancer (NSCLC) that can be divided into 3 major histologic subtypes: squamous cell carcinoma, adenocarcinoma, and large cell lung cancer. NSCLC is often diagnosed at an advanced stage and has a poor prognosis. Defects in TP53 are a cause of choroid plexus papilloma (CPLPA) [MIM:260500]. Choroid plexus papilloma is a slow-growing benign tumor of the choroid plexus that often invades the leptomeninges. In children it is usually in a lateral ventricle but in adults it is more often in the fourth ventricle. Hydrocephalus is common, either from obstruction or from tumor secretion of cerebrospinal fluid. If it undergoes malignant transformation it is called a choroid plexus carcinoma. Primary choroid plexus tumors are rare and usually occur in early childhood.[11] Defects in TP53 are a cause of adrenocortical carcinoma (ADCC) [MIM:202300]. ADCC is a rare childhood tumor of the adrenal cortex. It occurs with increased frequency in patients with the Beckwith-Wiedemann syndrome and is a component tumor in Li-Fraumeni syndrome.[12] Defects in TP53 are the cause of susceptibility to basal cell carcinoma 7 (BCC7) [MIM:614740]. A common malignant skin neoplasm that typically appears on hair-bearing skin, most commonly on sun-exposed areas. It is slow growing and rarely metastasizes, but has potentialities for local invasion and destruction. It usually develops as a flat, firm, pale area that is small, raised, pink or red, translucent, shiny, and waxy, and the area may bleed following minor injury. Tumor size can vary from a few millimeters to several centimeters in diameter.[13]
[P53_HUMAN] Acts as a tumor suppressor in many tumor types; induces growth arrest or apoptosis depending on the physiological circumstances and cell type. Involved in cell cycle regulation as a trans-activator that acts to negatively regulate cell division by controlling a set of genes required for this process. One of the activated genes is an inhibitor of cyclin-dependent kinases. Apoptosis induction seems to be mediated either by stimulation of BAX and FAS antigen expression, or by repression of Bcl-2 expression. In cooperation with mitochondrial PPIF is involved in activating oxidative stress-induced necrosis; te function is largely independent of transcription. Induces the transcription of long intergenic non-coding RNA p21 (lincRNA-p21) and lincRNA-Mkln1. LincRNA-p21 participates in TP53-dependent transcriptional repression leading to apoptosis and seem to have to effect on cell-cycle regulation. Implicated in Notch signaling cross-over. Prevents CDK7 kinase activity when associated to CAK complex in response to DNA damage, thus stopping cell cycle progression. Isoform 2 enhances the transactivation activity of isoform 1 from some but not all TP53-inducible promoters. Isoform 4 suppresses transactivation activity and impairs growth suppression mediated by isoform 1. Isoform 7 inhibits isoform 1-mediated apoptosis.[14][15][16][17][18][19][20][21][22][23][24]
About this Structure
2j20 is a 2 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA.
See Also
- Joerger AC, Ang HC, Fersht AR. Structural basis for understanding oncogenic p53 mutations and designing rescue drugs. Proc Natl Acad Sci U S A. 2006 Oct 10;103(41):15056-61. Epub 2006 Oct 2. PMID:17015838
- Joerger AC, Allen MD, Fersht AR. Crystal structure of a superstable mutant of human p53 core domain. Insights into the mechanism of rescuing oncogenic mutations. J Biol Chem. 2004 Jan 9;279(2):1291-6. Epub 2003 Oct 8. PMID:14534297 doi:10.1074/jbc.M309732200
- Joerger AC, Ang HC, Veprintsev DB, Blair CM, Fersht AR. Structures of p53 cancer mutants and mechanism of rescue by second-site suppressor mutations. J Biol Chem. 2005 Apr 22;280(16):16030-7. Epub 2005 Feb 9. PMID:15703170 doi:http://dx.doi.org/10.1074/jbc.M500179200
- ↑ Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD. Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A. 1999 Nov 23;96(24):13777-82. PMID:10570149
- ↑ Law JC, Strong LC, Chidambaram A, Ferrell RE. A germ line mutation in exon 5 of the p53 gene in an extended cancer family. Cancer Res. 1991 Dec 1;51(23 Pt 1):6385-7. PMID:1933902
- ↑ Malkin D, Li FP, Strong LC, Fraumeni JF Jr, Nelson CE, Kim DH, Kassel J, Gryka MA, Bischoff FZ, Tainsky MA, et al.. Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms. Science. 1990 Nov 30;250(4985):1233-8. PMID:1978757
- ↑ Srivastava S, Zou ZQ, Pirollo K, Blattner W, Chang EH. Germ-line transmission of a mutated p53 gene in a cancer-prone family with Li-Fraumeni syndrome. Nature. 1990 Dec 20-27;348(6303):747-9. PMID:2259385 doi:http://dx.doi.org/10.1038/348747a0
- ↑ Felix CA, Nau MM, Takahashi T, Mitsudomi T, Chiba I, Poplack DG, Reaman GH, Cole DE, Letterio JJ, Whang-Peng J, et al.. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia. J Clin Invest. 1992 Feb;89(2):640-7. PMID:1737852 doi:http://dx.doi.org/10.1172/JCI115630
- ↑ Malkin D, Jolly KW, Barbier N, Look AT, Friend SH, Gebhardt MC, Andersen TI, Borresen AL, Li FP, Garber J, et al.. Germline mutations of the p53 tumor-suppressor gene in children and young adults with second malignant neoplasms. N Engl J Med. 1992 May 14;326(20):1309-15. PMID:1565144 doi:http://dx.doi.org/10.1056/NEJM199205143262002
- ↑ Frebourg T, Barbier N, Yan YX, Garber JE, Dreyfus M, Fraumeni J Jr, Li FP, Friend SH. Germ-line p53 mutations in 15 families with Li-Fraumeni syndrome. Am J Hum Genet. 1995 Mar;56(3):608-15. PMID:7887414
- ↑ Varley JM, McGown G, Thorncroft M, Tricker KJ, Teare MD, Santibanez-Koref MF, Martin J, Birch JM, Evans DG. An extended Li-Fraumeni kindred with gastric carcinoma and a codon 175 mutation in TP53. J Med Genet. 1995 Dec;32(12):942-5. PMID:8825920
- ↑ Luca JW, Strong LC, Hansen MF. A germline missense mutation R337C in exon 10 of the human p53 gene. Hum Mutat. 1998;Suppl 1:S58-61. PMID:9452042
- ↑ Guran S, Tunca Y, Imirzalioglu N. Hereditary TP53 codon 292 and somatic P16INK4A codon 94 mutations in a Li-Fraumeni syndrome family. Cancer Genet Cytogenet. 1999 Sep;113(2):145-51. PMID:10484981
- ↑ Rutherford J, Chu CE, Duddy PM, Charlton RS, Chumas P, Taylor GR, Lu X, Barnes DM, Camplejohn RS. Investigations on a clinically and functionally unusual and novel germline p53 mutation. Br J Cancer. 2002 May 20;86(10):1592-6. PMID:12085209 doi:10.1038/sj.bjc.6600269
- ↑ Ribeiro RC, Sandrini F, Figueiredo B, Zambetti GP, Michalkiewicz E, Lafferty AR, DeLacerda L, Rabin M, Cadwell C, Sampaio G, Cat I, Stratakis CA, Sandrini R. An inherited p53 mutation that contributes in a tissue-specific manner to pediatric adrenal cortical carcinoma. Proc Natl Acad Sci U S A. 2001 Jul 31;98(16):9330-5. PMID:11481490 doi:10.1073/pnas.161479898
- ↑ Stacey SN, Sulem P, Jonasdottir A, Masson G, Gudmundsson J, Gudbjartsson DF, Magnusson OT, Gudjonsson SA, Sigurgeirsson B, Thorisdottir K, Ragnarsson R, Benediktsdottir KR, Nexo BA, Tjonneland A, Overvad K, Rudnai P, Gurzau E, Koppova K, Hemminki K, Corredera C, Fuentelsaz V, Grasa P, Navarrete S, Fuertes F, Garcia-Prats MD, Sanambrosio E, Panadero A, De Juan A, Garcia A, Rivera F, Planelles D, Soriano V, Requena C, Aben KK, van Rossum MM, Cremers RG, van Oort IM, van Spronsen DJ, Schalken JA, Peters WH, Helfand BT, Donovan JL, Hamdy FC, Badescu D, Codreanu O, Jinga M, Csiki IE, Constantinescu V, Badea P, Mates IN, Dinu DE, Constantin A, Mates D, Kristjansdottir S, Agnarsson BA, Jonsson E, Barkardottir RB, Einarsson GV, Sigurdsson F, Moller PH, Stefansson T, Valdimarsson T, Johannsson OT, Sigurdsson H, Jonsson T, Jonasson JG, Tryggvadottir L, Rice T, Hansen HM, Xiao Y, Lachance DH, O Neill BP, Kosel ML, Decker PA, Thorleifsson G, Johannsdottir H, Helgadottir HT, Sigurdsson A, Steinthorsdottir V, Lindblom A, Sandler RS, Keku TO, Banasik K, Jorgensen T, Witte DR, Hansen T, Pedersen O, Jinga V, Neal DE, Catalona WJ, Wrensch M, Wiencke J, Jenkins RB, Nagore E, Vogel U, Kiemeney LA, Kumar R, Mayordomo JI, Olafsson JH, Kong A, Thorsteinsdottir U, Rafnar T, Stefansson K. A germline variant in the TP53 polyadenylation signal confers cancer susceptibility. Nat Genet. 2011 Sep 25;43(11):1098-103. doi: 10.1038/ng.926. PMID:21946351 doi:10.1038/ng.926
- ↑ Schneider E, Montenarh M, Wagner P. Regulation of CAK kinase activity by p53. Oncogene. 1998 Nov 26;17(21):2733-41. PMID:9840937 doi:10.1038/sj.onc.1202504
- ↑ Guo A, Salomoni P, Luo J, Shih A, Zhong S, Gu W, Pandolfi PP. The function of PML in p53-dependent apoptosis. Nat Cell Biol. 2000 Oct;2(10):730-6. PMID:11025664 doi:10.1038/35036365
- ↑ Louria-Hayon I, Grossman T, Sionov RV, Alsheich O, Pandolfi PP, Haupt Y. The promyelocytic leukemia protein protects p53 from Mdm2-mediated inhibition and degradation. J Biol Chem. 2003 Aug 29;278(35):33134-41. Epub 2003 Jun 16. PMID:12810724 doi:10.1074/jbc.M301264200
- ↑ An W, Kim J, Roeder RG. Ordered cooperative functions of PRMT1, p300, and CARM1 in transcriptional activation by p53. Cell. 2004 Jun 11;117(6):735-48. PMID:15186775 doi:10.1016/j.cell.2004.05.009
- ↑ Ghosh A, Stewart D, Matlashewski G. Regulation of human p53 activity and cell localization by alternative splicing. Mol Cell Biol. 2004 Sep;24(18):7987-97. PMID:15340061 doi:10.1128/MCB.24.18.7987-7997.2004
- ↑ Zhao Y, Katzman RB, Delmolino LM, Bhat I, Zhang Y, Gurumurthy CB, Germaniuk-Kurowska A, Reddi HV, Solomon A, Zeng MS, Kung A, Ma H, Gao Q, Dimri G, Stanculescu A, Miele L, Wu L, Griffin JD, Wazer DE, Band H, Band V. The notch regulator MAML1 interacts with p53 and functions as a coactivator. J Biol Chem. 2007 Apr 20;282(16):11969-81. Epub 2007 Feb 22. PMID:17317671 doi:M608974200
- ↑ Taira N, Nihira K, Yamaguchi T, Miki Y, Yoshida K. DYRK2 is targeted to the nucleus and controls p53 via Ser46 phosphorylation in the apoptotic response to DNA damage. Mol Cell. 2007 Mar 9;25(5):725-38. PMID:17349958 doi:10.1016/j.molcel.2007.02.007
- ↑ Allton K, Jain AK, Herz HM, Tsai WW, Jung SY, Qin J, Bergmann A, Johnson RL, Barton MC. Trim24 targets endogenous p53 for degradation. Proc Natl Acad Sci U S A. 2009 Jul 14;106(28):11612-6. doi:, 10.1073/pnas.0813177106. Epub 2009 Jun 25. PMID:19556538 doi:10.1073/pnas.0813177106
- ↑ Huarte M, Guttman M, Feldser D, Garber M, Koziol MJ, Kenzelmann-Broz D, Khalil AM, Zuk O, Amit I, Rabani M, Attardi LD, Regev A, Lander ES, Jacks T, Rinn JL. A large intergenic noncoding RNA induced by p53 mediates global gene repression in the p53 response. Cell. 2010 Aug 6;142(3):409-19. doi: 10.1016/j.cell.2010.06.040. PMID:20673990 doi:10.1016/j.cell.2010.06.040
- ↑ Wu L, Ma CA, Zhao Y, Jain A. Aurora B interacts with NIR-p53, leading to p53 phosphorylation in its DNA-binding domain and subsequent functional suppression. J Biol Chem. 2011 Jan 21;286(3):2236-44. doi: 10.1074/jbc.M110.174755. Epub 2010 , Oct 19. PMID:20959462 doi:10.1074/jbc.M110.174755
- ↑ Vaseva AV, Marchenko ND, Ji K, Tsirka SE, Holzmann S, Moll UM. p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell. 2012 Jun 22;149(7):1536-48. doi: 10.1016/j.cell.2012.05.014. PMID:22726440 doi:10.1016/j.cell.2012.05.014
Proteopedia Page Contributors and Editors (what is this?)
Categories: Homo sapiens | Ang, H C. | Fersht, A R. | Joerger, A C. | Activator | Anti-oncogene | Apoptosis | Cell cycle | Disease mutation | Dna-binding | Dna-binding protein | Glycoprotein | Host-virus interaction | Li- fraumeni syndrome | Li-fraumeni syndrome | Metal-binding | Nuclear protein | P53 dna-binding domain | Phosphorylation | Second-site suppressor mutation | Superstable mutant | Transcription | Transcription regulation | Transferase | Tumor suppressor


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What do critical and strategic thinking, effective communication, working with modern technologies, and financial management have in common? They are all skills that are obtained as a result of completing NCC's Business Management program, which is accredited by the Association of Collegiate Business Schools and Programs (ACBSP) and is designed to send graduates directly into the business world.
The Business Management curriculum provides students with an inclusive background of methods and techniques that can be applied in many different types of business environments. These include marketing, finance, operations, human resources and law. Students learn through a combination of management principles, concepts and organizational operations. This, along with chosen electives throughout the program, helps students easily configure their degree to fit their personal goals.
The program culminates in a capstone experience called the International Business Practice Firm, where simulated company situations allow students to utilize the managerial techniques that they've acquired over four semesters.

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2002-05-15 / Opinion
A review of the issues shows where prior ASD board failed in its role Dear Editor,
For many months now I have been reading the ongoing debate over who were the villains and who were the saviors of the Park Avenues School construction project. Sam Williams
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(WJBK) -- Check out Taranza McKelvin's moves as he leads the Glades Central High School marching band in Belle Galde, Fla.The five-year-old went to band camp with the group over the summer and, as you can see, he caught on pretty quick. This on-field performance from Saturday was Taranza's debut. The band's director says we can expect to see him on the field in future performances as well.
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Terrence Jones was charged with a misdemeanor of harassment, alleged to have occurred in Portland, Oregon in the early morning of July 31, 2013. He is charged with intentionally harassing Daniel Kellerher by subjecting Mr. Kellerher to offensive physical contact. Neither the information from the District Attorney, which is the charging document, nor the Oregon Revised Statutes use the inflammatory term "stomp." Mr. Kellerher apparently was sleeping in a doorway next to a police precinct and was, in part, extended onto the sidewalk. The arresting officer did not determine whether Mr. Kellerher needed any medical attention. In fact, Mr. Kellerher received no medical attention and apparently needed none.
Terrence Jones denies the charge and, in fact, appeared in Multnomah County Circuit Court on July 31, 2013 where he entered a plea of not guilty. We believe that the case will be resolved favorably. We look forward to the next court appearance, scheduled for September 6, 2013.
Terrence Jones is a gentleman with not a mean bone in his body. He was raised by his mother and grandmother, two very strong and competent women, who taught him to treat people, no matter who they are, with respect and kindness. While acknowledging that Terrence may not have been looking where he was walking, with a crowd that had spilled out into the street and were being herded by the police back onto the sidewalk, Terrence tripped over Mr. Kellerher. He did yell at him to "wake up" and may have nudged him. He certainly would not, and did not, intend to cause Mr. Kellerher any harm. He is confident that those who know him understand that the charge and accusation that Terrence intentially committed a crime cannot be true. It is inconsistent with his character. Terrence is thankful for all who continue to support him and understand the great sadness he is suffering as the result of this incident.
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Guy Sebastian debuted the artwork for new single "Like A Drum" earlier this week. The 31-year-old looked pretty glum on the cover, so I expected something serious and hard-hitting. As it turns out, the track — out today in his native Australia — is an infectious soul-meets-dance gem in the tradition of Avicii's "Wake Me Up". Go figure!
No doubt, the inaugural Australian Idol winner is hoping to capitalize on the success of Lupe Fiasco-assisted breakthrough hit "Battle Scars" and he should find a lot of love from radio programmers with this. "Like A Drum" expertly taps into the electro-house craze but still serves up an easily digestible chorus and showcases Guy's soulful pipes. Listen to the future hit after the jump.
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|By Jennifer Hutchison
Article Rating:
|February 11, 2013 08:00 AM EST
Professionals who work in the service field often have to juggle several tasks at once. Service techs have to make sales presentations and deal with customer service and still fix the problem they were hired for. They're basically a one-man show that travels from site to site, the ultimate multi-tasker, with so many projects and phone calls to handle that a person can't help but wonder how most even survive each day. But there's something out there to help these guys out with their busy life. By working in the cloud, contractors and techs can gain an extra pair of arms to make each day count.
When your techs show up to a job they bring their toolbox and a bulky laptop. Their hands are extremely full. Everything they need to know is on that computer but it takes minutes to load, and they have to be on the phone at the same time talking to the office. If a problem should arise, they may have to leave the site and only return after obtaining the information or ordering the parts that they need. Then what happens if there are errors in that information? They have to head back again to the office. The tech wastes gas and the client wastes time. No one's a winner here.
With your current setup, your service techs might not have access to immediate information because it's all manual. The situation could be improved with instant access to what is needed: information. With the cloud, your techs would be able to pull out their phones to access job, client, and other information instantly, not to mention replacing that bulky laptop with a slim smartphone that'll fit in any pocket.
When working in the cloud, there are no risks or compromises, only faster, better, and more accessible tools for communication. The smartphone becomes just as important as the wrench in a plumber's toolbox.
It'll Always Be There
What happens now when a loyal long-term client calls for a tech to solve a problem? The job is scheduled for the next day and files have to be sorted through at lightening speeds to obtain the right info. Sometimes a different worker is assigned to a job and hasn't talked to the previous tech. What if the files were lost or thrown away? If your tech is working in the cloud, going back to visit an old job or obtaining a new job from a loyal client isn't a big deal. They can have previous notes and billing statements available on-demand. All they need to do is open the app on their phone to see every note anyone in the company ever made. The same thing goes for a different tech visiting the same job. Every worker has access to a large amount of data that is available at the click of a button. Managers will also be able to see what projects techs are working on. Never again will your techs say "I wasn't the technician on that job", everyone will be able to work together with the same access to information. Best of all, the information is safe, secure, and always within reach.
Even years later the information will still be there, ready to be used when fixing another sink or repairing more ducts. With cloud providers keeping your information safe, wouldn't it be a safer, better idea to be working in the cloud?
When Hammer Meets Nail
The cloud is growing, and using it to manage your business means simplifying a complex and slow process. Managers can see directly what projects are being worked on and can participate in helping those projects move smoothly.
Say for instance, your company receives a service call from a new client. You make a few notes: "Customer says sink is backed up" or "AC unit won't turn on". You then send a truck to visit the client. With the cloud, the tech snaps pictures and enters notes into his mobile device, and you can read everything he does from your own office computer. You instantly notice that it's a different problem and not the one he seems to suspect. You send him an alert, and together devise a new proposal to hand to your client. You're able to instantly accept the proposal and email or print it out to put into your client's hands. You show the client that you're on the top of your game and secure the job. After they accept, you send out invoices and orders for parts needed for the job. Your consultant puts on his tech hat and gets to work. At every step, you and your tech can stay in touch with each other and the client, just in case more problems arise. There are no nasty surprise additions to the estimate because you have access to all of the information needed to fix the problem.
You are able to communicate with your on-site consultant/tech and together you both achieved your goal: to satisfy the customer with fast high-quality service. There's no doubt that the customer will refer you to friends and family, and will probably call you back in the future if some other problem comes up.
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Hi, has anyone ever tried to google this? /wp-content/uploads/album
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I'm using this wonderful plugin for my site but I need to avoid this problem. I need that people of my commnity who create albums will be able to keep them private.
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Join us for an all-day field trip experience. Guide your students to various stations throughout Minnetrista's campus for a fun and educational exploration of thematic topics. Students can participate in school tours in addition to the Field Days to gain further hands-on experiences.
Field Days are 4-hour experiences.
$6/student (unless otherwise noted)
Field Days
Johnny Appleseed
Friday, September 30 & Friday, October 7
9:30 a.m.–1:30 p.m.
Grades K–2
There are two opportunities for your students to enjoy a whole day of learning the science and history of apples. Students will engage in hands-on experiences that will give them valuable understanding of life cycles, plants and, of course, Johnny Appleseed.
What will my students do?
- Meet Johnny Appleseed
- Get a behind-the-scenes look at Minnetrista's apple pressing machines at work
- Stroll through our orchard while the fruit is harvested by gardeners
- Make cider with a hand-crank press
- Create an educational apple craft
- Take an apple home with them
- And much more!
What will my students learn?
- Understand that Johnny Appleseed (actually John Chapman) was a real figure in history
- Use their five senses to determine differences in both trees and apples
- Examine and understand how machines have changed over time and have impacted how we get the goods we need and want
- Understand that a tree and the fruit that grows on it is a living thing with a specific process
- Learn the roles of people who help us to obtain our food
- Identify the anatomy of an apple
State Standards
|Language Arts
|Social Studies
|1st Grade
|7.1, 1.7.2, 1.7.5, 1.7.10
|1.1.1, 1.4.2, 1.4.3, 1.4.4, 1.5.3, 1.6.2
|1.1.1, 1.1.2, 1.1.4
|2nd Grade
|2.7.1, 2.7.2, 2.7.7, 2.7.14
|2.1.1, 2.1.2, 2.1.6, 2.3.1, 2.3.4, 2.4.1, 2.4.3, 2.4.4,
|2.1.1, 2.4.2, 2.4.4


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411's WWE Smackdown Report 2.1.13
Posted by
Michael Benjamin
on 02.01.2013
Alberto Del Rio wrestled Dolph Ziggler, Team Hell No fought Sin Cara and Rey Mysterio, Damien Sandow battled Sheamus, Jack Swagger made his return and more! Check out 411's full WWE Smackdown report for all of the details!
Michael Benjamin here! We're officially on the Road to Wrestlemania now and the quality of this week's Raw was indicative of that. Let's see if Smackdown can follow suit! Can I get a logo?
Championship Roll Call:
WWE Champion:
The Rock
World Champion:
Alberto Del Rio
US Champion:
Antonio Cesaro
IC Champion:
Wade Barrett
Unified Diva's Champion:
WWE World Tag Team Champions:
Kane & Daniel Bryan
WWE Smackdown Report 2.01.13
- Alberto's backstage in street clothes holding a lead pipe. We're told that he's awaiting Big Show's arrival. Big Show must have left his lead pipe at Alberto's house.
- Booker T and Teddy Long are standing in the ring with Khali, Sheamus, Daniel Bryan, Kane, and Randy Orton. Dolph Ziggler is standing outside of the ring with AJ and Langston. Six men in February!? What are you about to do, Book? Booker T says that we're here to decide who will challenge for the World Heavyweight Championship in this year's Elimination Chamber. JACK F'N SWAGGER interrupts to a chorus of (canned) boos. He has great interrupting music. Swagger says that he's been living the life of a real American. He says that he's been at home watching everything and that he's disappointed with the direction WWE is heading in. Swagger says that he wants in the Elimination Chamber match! When Booker T mentions that all of the spots are filled, Ziggler is quick to bow out of the match. People read the spoilers and bitched about the logic behind Ziggler's decision to not partake but he explained it well enough. Why would he want to participate in one of the most brutal and barbaric matches in the WWE? He can sit back and do nothing (while avoiding possible injury) and still have his title shot. "Babe, E, we're out of here!". Booker T says that he knew Ziggler would chicken out of the Chamber match. Book says that he can't chicken out of his match with Alberto tonight though. He says that all six men in the ring will be in action tonight and as long as they impress him, they're in the chamber match. Booker T gets very excited as he announces a TAG TEAM MATCH, Team Hell No vs Cara and Rey is booked. AND IT'S NEXT!
Commercial Break
Team Hell No vs. Rey Mysterio & Sin Cara
Mysterio and Kane start us off. Rey's on fire right out of the gate. Kane ends up on the outside and gets hit with a sitting senton. Rey tags in Sin Cara and Kane quickly takes control. He stomps Cara in the corner and makes the tag in to Bryan. Bryan gives Cara an Irish whip into the corner but gets hit with a flipping back elbow. Mysterio and Kane are back in quick. Kane delivers a stiff right to Mysterio and tags in Bryan. He Irish whips Bryan into a cornered Mysterio and Bryan hits the running missile drop kick. Mysterio reverses an Irish whip and sets Bryan up for the 619 but Bryan rolls to the outside. It's probably a good time to head to...
Commercial Break
We're back as Daniel Bryan lets loose of an ARM BAR on Sin Cara. Daniel Bryan hits a ridiculous missile drop kick on Sin Cara. I'd like to see Bryan go one on one with both of these guys for an extended length of time. Bryan locks the surfboard submission on Sin Cara! He gets one of his hands free to tag in Kane. Kane delivers a dropkick to a trapped Cara. Kane follows up with a nice sideslam for TWO. He puts Sin Cara up top for a superplex but Cara fights off and attempts a crossbody! Kane catches him but Sin Cara reverses that into a wicked DDT! Both men down! Hot tag time! Mysterio hits a flash rana on Bryan and hits a fourth seated senton on Bryan. Bryan rolls through a pinfall predicament but gets caught with a dropkick for his efforts. Rey goes for a 619 but Kane gets the interception! He goes for a chokeslam but Mysterio gives him the rana to the outside! Rey turns around and gets caught in the Lebell lock! Cara back in to break up the hold. Sin Cara sees Kane getting up outside and hits a 1, 2 Moonsault over the top! Mysterio finally hits Bryan with the 619 and drops the splash off the top rope for three! Wow! That was a great opener. The first half met my expectations and then they kicked it all the way up after the commercial break, blowing my expectations out of the water with a hot closing sequence. I can't wait for the rematch.
: Sin Cara and Rey Mysterio @ 9:00 aired via pinfall
-Commercial Break-
- Matt Striker tries to get a word with Alberto in the parking lot. Alberto says that he's trying to get some fresh air and to leave him alone. I'm 100% on face Alberto's bandwagon at this point.
The Great Khali (w/ Natalya and Hornswoggle) vs. Jinder Mahal (w/3MB)
Khali hits a chop and smashes Jinder's head in the corner. CHA-CHOP. Drew McIntyre tries getting involved and the ref calls him out on it. "I'm done referee, I'm done!" Drew can work both sides very well. That will give his career some longevity. Khali hits like four more chops and then sets up for another chop. I assume this chop over the head will hurt more than the others because he signaled for it beforehand. Slater gets on the apron for the distraction and Khali knocks him off. Khali turns around and finishes off Jinder. I'm generally a VERY positive guy when it comes to wrestling but can we just stop with Khali already? At the very least, book him SPARINGLY. I don't need to see this shit every time I watch current product.
: The Great Khali @ around 1:30ish via pinfall
- Booker T and Teddy Long are watching Smackdown on their TV backstage. Booker says that he was surprised about Swagger's return. Teddy reveals that it was his doing. Before Booker can react to that, Cody and Damien interrupt and say that they're pursuing singles competition starting now. They hug it out and say that they're still best friends. Booker T says that he's happy about this decision. It gives Damien a chance to wrestle Sheamus in a Raw rematch tonight. I think these guys still had some mileage. Hopefully they have plans for both men moving forward. Sandow's booked and Cody's not so there is that.
-Commercial Break-
: We get a personal performance review recap. Like i said in the Main Event recap, Heyman was pure gold here. Both in the ring and in the pretape. The two sides of his personality being presented in two different fashions back to back really showed the depth of his character and what Paul Heyman, the man, is capable of. I thought the whole thing was very well executed.
-Commercial Break-
- Alberto's still in the parking lot waiting for Big Show.
- We get a recap package of Cena winning the Rumble match and his segment on Raw. Are they going to do The Shield vs Sheamus, Ryback, and Cena in the chamber? I hope so.
Damien Sandow vs. Sheamus
They exchange flurries of offense before Sandow roles to the outside. Sheamus follows him out and then back in, getting met with some boots from Sandow upon re-entry. Oh, faces. You'll never learn. Sandow dominates now. An Elbow of Disdain gets a two count. Sheamus tries fighting back but Sandow maintains control. Sandow hits a couple of clotheslines and goes for white noise. Sandow rolls off on to the apron and Sheamus delivers the CLUBBERING BLOWS. By clubbering blow number 4, Shield's music hits! Sheamus is standing his ground just like Cena did. He hits a Brogue on Rollins. Reigns and Ambrose take care of Sheamus and the crowd is chanting "feed me more" VERY loudly. Good for Ryback! They get Sheamus with the powerbomb and bounce shortly thereafter. Jeez, nobody wanted to help him out?
: Sheamus @ 4:30 via DQ
-Commercial Break-
Randy Orton vs. Wade Barrett
Orton corners Barrett quickly and Irish whips him into the adjacent corner. He follows up with a dropkick and Barrett roles to the outside. Barrett takes a quick breather before stepping in at five. He delivers a knee to the abdomen and works Orton into the corner now. Orton quickly fights out with a collection of rights. Barrett bounces off the ropes though and hits a big boot to get in control. TWO COUNT. Barrett catches Orton up in the ropes and hits a big boot. He pulls Orton through the ropes and Barrett gets a near fall. He locks in a headlock that Orton is quick to fight out of. Orton snapmares out of it. He hits his powerslam and "goes to that place". He goes for the rope assisted DDT but that's a no go as Wade rolls out. He follows Barrett to the outside and pushes Orton into the ring post. He charges with a Bull Hammer but Orton ducks! Bull Hammer into the ring post. Orton hits that rope assisted DDT and an RKO for the win. It was a quick sprint but it was fun while it lasted. I would have liked to see Barrett look like more of a threat but the format of tonight's show doesn't really lend well to that.
: Orton @ 4:10 via pinfall
-Commercial Break-
Jack Swagger vs. Kofi Kingston
So it looks like Kofi is the JTTS on the Road to Wrestlemania. Swagger just dominates right out of the gate, tossing Kofi around like a rag doll. He hits a Vader Bomb for two. Swagger looking very good in here. He chokes Kofi on the bottom rope for a moment before backing off. Kofi tries to mount some offense and hits a springboard crossbody for two. Swagger gets up and turns him inside out with a clothesline. Kofi fights out of an ARM BAR. A very brutal looking ARM BAR at that. Swagger doesn't let him take control and backs him into a corner. Kofi monkey flips his way out of that. Swagger charges and here comes Kofi! Running open palm strike followed by a boom drop! Kofi signals for Trouble in Paradise but Swagger catches him, throws him into the corner, and that THAT gets reversed into a pendulum kick by Kofi. Swagger to the outside! Kofi goes for a sliding dropkick under the bottom rope and misses! Swagger whips him into the stairs but Kofi jumps over them! He hits catches Swagger with a clothesline! Kofi goes for a huge Trouble in Paradise but SWAGGER DUCKS! Kofi's foot lands right on the announce table in a sick looking crash! Swagger rolls him in and boots him in the face. Ankle Lock. It's over! These guys packed a lot of action into the time they were allotted and Swagger looks great in his return.
: Jack Swagger @ 6:12 via submission
- Security is with Alberto in the parking lot and they tell him to put the pipe down. Big Show's RV arrives on the scene and Alberto ducks for cover behind an SUV. How nice of Show to get to the arena before Smackdown ends. Apparently Big Show drives his own RV as well. Alberto runs out from the shadows and attacks Big Show with the pipe. Big Show is on top of a car trying to avoid pipe shots. Alberto nails him in the leg with the pipe and Show falls on to the top of the car. Alberto is talking smack in Spanish the whole time and Big Show is all "come on man!" Big Show finally gets in a car and escapes. It's pretty refreshing to see a face that isn't so ridiculously cookie cutter. Pretty good segment. Both guys have a really good handle on their character.
-Commercial Break-
Raw Rebound Part 2
: We get a recap of the Punk/Rock altercation on Raw.
-Commercial Break-
- Backstage, Alberto tells Ricardo to stay in the locker room. That's a great idea because Big Show is gone, you know?
Dolph Ziggler (w/ AJ and Big E) vs. Alberto Del Rio
I'M HERE TO SHOW THE WORLD. We get a nice arm lock exchange to start off the match. Alberto wins that exchange and works Ziggy into the corner. Ziggler down. Alberto goes for a moonsault and Dolph moves. Alberto lands on his feet! Dolph charges Alberto but gets belly flopped. Del Rio charges at Ziggler in the corner but Ziggler dodges it and Del Rio goes into the post. Ziggler hits a huge DDT for two. He hits an elbow drop for another two. Dolph locks in a side headlock to maintain control. Alberto makes it to his feet and shoots him off. Alberto hits a German suplex! He goes to the second rope and goes for the moonsault again but Big E trips him up and he lands on his left shoulder! AJ was distracting the ref. Same landing he took through the table at the Rumble. Ziggler picks him and goes for an Irish Whip. Alberto dropkicks Big E instead of hitting the ropes! The ref sends Big E to the back! Dolph is shocked like this is the first time Big E has been sent to the back.
-Commercial Break-
Alberto and Ziggler exchange punches as we return from commercial break. Ziggler goes upstairs and Alberto catches him and crotches him. He follows up with a chop and a superplex off the top! If I had a dollar for every time Matthews called AJ a mastermind... Both men down. They make it to their feet by 4 and Ziggy gets the first punch. He gets Alberto in the corner and punches away. Alberto gives him the Snake Eyes and here we go! He hits two clotheslines, ducks a clothesline, and delivers a tilt-a-whirl back breaker! Ziggler gets to his knees and there's a boot the jaw. Dolph reverses a cross arm breaker into a fameasser for two! Alberto gets Dolph caught up in the top rope! He hits two kidney punches and a back breaker for two! Alberto still utilizes the five count like a heel which doesn't go over JBL's head. Alberto comes off the top for an ax handle and gets caught with a huge dropkick for two! Del Rio ducks a punch and locks in the cross arm breaker for the win! These two put in a very good match that built up to a very nice ending.
: Alberto Del Rio @ 10:00 via submission
- Post-match Big Show is on the tron and he has Ricardo. He says that if Alberto ever attacks him like that again, Show will hurt him. Big Show makes Ricardo beg to be let go. Big Show says he's going to let him go but not before a KO punch. Alberto runs to the back and Big Show is already gone.
: Tonight's Smackdown was a pretty solid episode. The wrestling was all good and everybody on the card seems to have some direction (Besides Khali). I'm really digging Big Show and Alberto's feud too, They're doing a great job getting the audience invested their rivalry. That's something that the blue brand doesn't always excel at. Thumbs up.
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ZOMG YOU GUYS! KATE MIDDLETON WANTS A KID! More
ZOMG YOU GUYS! KATE MIDDLETON WANTS A KID! More
During her current trip to Canada, Kate Middleton has showcased her style as a newly minted royal wife. Here are some photos of what she's worn so far. More
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Okay, think about how much the most expensive vacation you've ever taken has cost. Now double that… More
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Today is June 30th, which means that tomorrow is July 1st. Oh, and it's also Canada Day. As the French say, "bon fête du Canada!" Translation: good party of Canada. Not only is wearing un- patriotic attire on a national … More


text:
The Faces Of New York's Subway Commute
What did 2012 look like on New York City's subways? From video journalist Rebecca Davis's perspective, it was a mix of loneliness, intimacy, exhaustion, and, of course, smart phone-gazing. Davis's video Commuters 2012 is a voyeuristic glimpse of life in New York's connective tissue, the subway—hundreds of snapshots of regular people living their lives underground, selected from more than 3,000 photos she took last year.
"So often on the train we bury ourselves in something we're reading or music we're listening to and forget to look around and take in some great human drama that is constantly being played out in New York," Davis says. The best moments in her video are of children and of couples—kissing, laughing, or just sitting there. "I hope it makes people stop and look more deeply into all the different faces and human moments we encounter each day in a city like New York where privacy is hard to come by."
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The Faces Of New York's Subway Commute By fastcompany What did 2012 look like on New York City's subways? From video...
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Aggghhhh, makes me miss home…. I love taking public transport in the city. #strangers #peoplewatching
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text: Duluth, MN (KDAL) - Classes have resumed at Lincoln Park Middle School after the facility was locked down this morning. The Duluth School District says the incident grew from of an incident at the home of a student in which they told their parent that they'd have to pick them up at the jail because they were going to bring a gun to school. The parent alerted authorities, who placed the school in lockdown. A short time later the student in question was located by officers and taken into custody. No specific threats were made. The lockdown lasted about a half hour.


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Need a part-time (29.5 hours per week) reference librarian. ALA accredited master's degree in library science required. Some weekend work (in rotation with other reference staff). Looking for a go getter who embraces digital trends:) MUST apply online through the City of Kingsport's website – they will have the posting up for about 2 weeks.
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For close to eight years I have watched George Bush piss away a comfortable surplus and plunge us into a huge deficit; fritter away decades of goodwill overseas; use outright lies to launch an endless war; display callous disregard to fellow Americans during natural disasters; play cowboy while our economy sank into the mud; and […]
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Targeting a Common Characteristic of Advanced Tumors
Name of the Trial
Principal Investigators
Why This Trial Is Important
The FDA-approved chemotherapy drug topotecan is one of only a few agents that have shown the ability to inhibit HIF-1a in laboratory studies. Animal studies conducted by Dr. Melillo and his colleagues suggest that giving topotecan at lower doses over a longer period of time can reduce the level of HIF-1a in tumors and inhibit angiogenesis.
In this trial, doctors are testing the ability of topotecan to inhibit HIF-1a production and prevent tumors from growing and spreading further.
"HIF-1a gives tumors a selective growth advantage," said Dr. Kummar. "We're hoping to exploit a novel characteristic of an FDA-approved drug to take away this selective advantage and cause tumors to stop growing."
Who Can Join This Trial
Study Sites and Contact Information
An archive of "Featured Clinical Trial" columns is available at http://cancer.gov/clinicaltrials/ft-all-featured-trials.


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Making Old Lungs Look Young Again, With IbuprofenOct. 2, 2014 The lungs become more inflammatory with age, researchers say, and add that ibuprofen can lower that inflammation. Immune cells from old mouse lungs fought tuberculosis bacteria as effectively as ... full story
New Molecule Fights Oxidative Stress; May Lead to Therapies for Cancer and Alzheimer'sOct. 1, 2014 Breathing oxygen helps the body create energy for its cells. As a result of the breathing process, reactive molecules called 'free radicals' are produced that often cause damage to proteins ... full story
Decreased Ability to Identify Odors Can Predict Death: Olfactory Dysfunction Is a Harbinger of MortalityOct. 1, 2014 The inability of older adults to identify scents is a strong predictor of death within five years. Almost 40% of those who failed a smelling test died during that period, compared to 10% of those ... full story
Memory Loss Associated With Alzheimer's Reversed: Small Trial Succeeds Using Systems Approach to Memory DisordersSep. 30, 2014 In the first, small study of a novel, personalized and comprehensive program to reverse memory loss, nine of 10 participants displayed subjective or objective improvement in their memories beginning ... full story
Longitudinal Report Shows Challenging Reality of Aging With an Intellectual DisabilitySep. 30, 2014 The serious, complex and unique health and social challenges facing Ireland's intellectual disability population are outlined in a new report. The study is the first study of its kind in Europe ... full story
Protein That Causes Frontotemporal Dementia Also Implicated in Alzheimer's DiseaseSep. 29, 2014 Low levels of the naturally occurring protein progranulin exacerbate cellular and cognitive dysfunction, while raising levels can prevent abnormalities in an Alzheimer's ... full story
Signature of Aging in Brain: Researchers Suggest That the Brain's 'Immunological Age' Is What CountsSep. 29, 2014 Evidence of a unique 'signature' that may be the 'missing link' between cognitive decline and aging has been found by researchers. The scientists believe that this discovery may ... full story
Remote Healthcare for an Aging PopulationSep. 29, 2014 An aging population and an increased incidence of debilitating illnesses such as Parkinson's and Alzheimer's disease means there is pressure on technology to offer assistance with ... full story
Glaucoma Drug, Weight Loss Combo Tested to Restore VisionSep. 26, 2014 A blinding disorder, idiopathic intracranial hypertension (IIH), affects overweight young women. It is a condition, of unknown origin, causing raised intracranial pressure primarily in obese women. ... full story
Think You Have Alzheimer's? You Just Might Be Right, Study SaysSep. 24, 2014 New research suggests that people who notice their memory is slipping may be on to something. The research appears to confirm that self-reported memory complaints are strong predictors of clinical ... full story
The Plus Side of Population AgingSep. 24, 2014 An aging society will have numerous benefits, according to new research. Investigators say that population aging and the compositional changes that go along with it -- such as increasing education ... full story
Alzheimer's Patients Can Still Feel Emotion Long After Memories Have VanishedSep. 24, 2014 A new study further supports an inescapable message: caregivers have a profound influence -- good or bad -- on the emotional state of individuals with Alzheimer's disease. Patients may not ... full story
Multi-Function Protein Is Key to Stopping Genomic Parasites from 'Jumping'Sep. 23, 2014 Most organisms, including humans, have parasitic DNA fragments called 'jumping genes' that insert themselves into DNA molecules, disrupting genetic instructions in the process. And that ... full story
Putting Dementia Carers in ControlSep. 22, 2014 Experts will explore how improved support and powers for people caring for loved-ones with dementia can improve quality of life for both patients and carers around the UK as part of a new ... full story
On/off Switch for Aging Cells Discovered by ScientistsSep. 20, 2014 An on-and-off "switch" has been discovered in cells that may hold the key to healthy aging. This switch points to a way to encourage healthy cells to keep dividing and generating, for example, ... full story
Pathway That Contributes to Alzheimer's Disease Revealed by ResearchSep. 19, 2014 A defect in a key cell-signaling pathway has been discovered that researchers say contributes to both overproduction of toxic protein in the brains of Alzheimer's disease patients as well as loss ... full story
Simple Test Can Help Detect Alzheimer's Before Dementia Signs Show, Study ShowsSep. 19, 2014 A simple test that combines thinking and movement can help to detect heightened risk for developing Alzheimer's disease in a person, even before there are any telltale behavioural signs of ... full story
Down Syndrome Helps Researchers Understand Alzheimer's DiseaseSep. 18, 2014 The link between a protein typically associated with Alzheimer's disease and its impact on memory and cognition may not be as clear as once thought, according to a new study. Researchers looked at ... full story
Melanoma Risk Found to Have Genetic DeterminantSep. 18, 2014 Longer telomeres increase the risk of melanoma, researchers report, suggesting that melanoma risk has a genetic determinant. Telomeres are a part of the genome that function like the plastic caps of ... full story
Professional Recommendations Against Routine Prostate Cancer Screening Have Little EffectSep. 18, 2014 The effect of guidelines recommending that elderly men should not be routinely screened for prostate cancer "has been minimal at best," according to a new study. The review focused on the use of ... full story
- New molecule fights oxidative stress; May lead to therapies for cancer and Alzheimer's
- Decreased ability to identify odors can predict death: Olfactory dysfunction is a harbinger of mortality
- Memory loss associated with Alzheimer's reversed: Small trial succeeds using systems approach to memory disorders
- Longitudinal report shows challenging reality of aging with an intellectual disability
- Protein that causes frontotemporal dementia also implicated in Alzheimer's disease
- Signature of aging in brain: Researchers suggest that the brain's 'immunological age' is what counts
- Remote healthcare for an aging population
- Think you have Alzheimer's? You just might be right, study says
- The plus side of population aging
- Alzheimer's patients can still feel emotion long after memories have vanished
- Pathway that contributes to Alzheimer's disease revealed by research
- Simple test can help detect Alzheimer's before dementia signs show, study shows
- Down Syndrome helps researchers understand Alzheimer's disease
- Melanoma risk found to have genetic determinant
- Professional recommendations against routine prostate cancer screening have little effect
- Researchers corroborate neuroprotective effects of Sirtuin 1 activation on mice with Alzheimer's disease
- In mice, vaccine stops urinary tract infections linked to catheters
- Mechanism behind age-dependent diabetes discovered
- Treating insomnia in elderly reduces inflammation, lowers risk for chronic diseases
- World Alzheimer Report 2014 reveals persuasive evidence for dementia risk reduction
- Statin treatment among over-80 age group must always be assessed individually
- Neuroimaging technique identifies concussion-related brain disease in living brain
- New recommendations for treating urinary incontinence in women
- Cardiorespiratory fitness can delay male, age-associated blood pressure hikes
- Prostate cancer patients who receive hypofractionated radiation therapy report consistent quality of life before and after treatment
- Vitamin E intake critical during 'the first 1,000 days'
- New knowledge of genes driving bladder cancer points to targeted treatments
- Age, diabetes duration linked to risk of death, macrovascular complications
- Molecular mechanisms of birth defects among older women: Why older women can have babies with Down Syndrome
- Steroid hormone to fight age-related diseases
- Even small stressors may be harmful to men's health, new research shows
- Fish, fatty acid consumption associated with lower risk of hearing loss in women
- Appetite and mortality: The two are closely connected in the eldery
- Air pollution harmful to young brains, study finds
- Less effective DNA repair process takes over as mice age
- Long-term use of pills for anxiety and sleep problems may be linked to Alzheimer's
- Birth measurements could predict lung health in teen years
- How age alters our immune response to bereavement
- Biologists delay the aging process by 'remote control'
- Targeted immune system booster removes toxic proteins in mouse model of Alzheimer's disease
- Facial plastic surgery can safely address major aspects of aging in one operation
- Sleeping on animal fur in infancy found to reduce risk of asthma
- Poor recording of physical health, medication could be causing dementia trials to fail
- Diabetes mellitus, mild cognitive impairment: Higher risk in middle age?
- Mirabegron for overactive bladder: Added benefit not proven
- Marijuana compound may offer treatment for Alzheimer's disease, study suggests
- Lifetime of fitness: Fountain of youth for bone, joint health?
- Complication risk of deep brain stimulation similar for older, younger Parkinson patients
- Mindfulness training for memory impaired, their caregivers
- APOB, a gene involved in lipid transport, linked to cases of familial extreme longevity
- Train your heart to protect your mind
- Tissue regeneration using anti-inflammatory nanomolecules
- Creating pomegranate drug to stem Alzheimer's, Parkinson's
- Treatment for overactive bladder and irritable bowel syndrome advanced through pioneering research
- Steep decline in tooth loss, increase in socioeconomic disparities found by study
- Early to mid-life obesity linked to heightened risk of dementia in later life
- Investigational therapy focuses on slowing progression in mild to moderate Alzheimer's
- Why elderly are prone to sleep problems
- Taking pulse of aging of the brain
- Happiness in schizophrenia: Research suggests mental illness doesn't preclude enjoying life
- Music to your ears? Evidence of damage to hearing from music
- Women seek anti-aging clinicians to treat menopausal symptoms, study finds
- Decline in daily functioning related to decreased brain activity in Alzheimer's
- Mental health disparities higher for older African American adults
- Pinpointing genes that protect against frailty
- Most misdiagnosed form of dementia leaves patients, doctors unprepared
- Elderly with depression, mild cognitive impairment more vulnerable to accelerated brain aging
- Powerful new system for classifying tumors revealed
- New glycan creams, micronutrient creams hold promise for reducing signs of aging skin
- Link between vitamin D, dementia risk confirmed
- Dementia risk quadrupled in people with mild cognitive impairment
- Poor hearing confines older adults to their homes
- Childhood coxsackie virus infection depletes cardiac stem cells, might compromise heart health in adults
- Biochemical mechanisms contributing to fibromuscular dysplasia discovered
- Key to aging immune system: Discovery of DNA replication problem
- Researchers focus on role of the protein progerin in atherosclerosis in both modern and ancient times
- Depression as a risk factor for dementia: Link is independent of dementia-related brain changes
- Telephone support program beneficial for caregivers of those with dementia: Helps reduce symptoms of caregiver depression, health issues
- Bladder cancer patients identified who could benefit from 'tumor-softening' treatment
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Narrow your search
With a beautiful screen, refined interface, and huge coffer of media consumption options, the Amazon Kindle Fire HD is the Kindle Fire as it should have been.
The Bevometer keeps track of how many drinks you have had. Every time a drink is inserted, the counters go up by one.
The social network for professionals has dramatically altered the mobile experience to suck members into a personalized stream of business content.
How much does it cost to run your TV? The answer may surprise you.
Chip giant plans to make Ivy Bridge more power efficient than the versions that are currently used in the MacBook Air and Windows 8 ultrabooks.
Social-networking sites grew from 9 percent to 19 percent as a source for news in the last two years, but only 3 percent of respondents say they regularly get news from Twitter.
Chip giant will talk about a new series of mainstream chips next week that are much more power efficient than today's processors.
Online video has reached the tipping point. What will cable providers and content producers do to keep us glued to TV?
CNET sits down with CTO David Small to ask him about the network, what he thinks of the competition, and why the company eliminated its unlimited mobile data plan.
Grab your emergency underpants and strap on your bibs -- Porsche's just released the world's first videos of its 918 Spyder -- the achingly beautiful, ridiculously quick hybrid hypercar


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Perfect for all of your rubber stamping and paper crafts.
- Our rubber stamps are made in the USA of premium red rubber with static cling mounting cushion.
- 1.2.3. EZ to use! Remove the paper liner from the static cling cushion.
- Your rubber stamp is ready to be temporarily mounted on an acrylic block for stamping . . Easy Peasy!


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About Face Theatre
All American Mortgage Corporation
Tom Mikesell
1355 S. Rt. 59, Suite 2B
Naperville, IL 60564
Equal Housing Opportunity Lender
Illinois Residential Mortgage Licensee
Alliance Printing
Addison, IL 60101
ARK Porcelain Refinishing Service
165 Prairie Lake Road. Suite B, East Dundee, IL 60118
Tel: 773.763.6600 Tel: 847.836.1872
Fax: 847.836.1896
Atlantic Public Adjusting
AWM Construction
|700 Bonded Pkwy
|Streamwood, IL 60107
Ready to Make the Move? Discover the City of Berwyn's charming bungalows, distinct neighborhoods, and nightlife destinations. Only eight miles from the Loop, Berwyn welcomes you with open arms. Visit www.whyberwyn.com or call 708-788-8100 for more information.
Ready to Make the Move
Berwyn Kia
"You always win at Berwyn Kia! Call or stop by today!"
Best Vacuum
Camp Kupugani
6903 W. White Eagle Rd.
Leaf River, IL 61047
Chicago Gadgets
Chicago History Museum
The Chicago History Museum cares for, showcases, and interprets millions of authentic pieces of Chicago and U.S. History. If you live in Chicago or are here to visit and are curious about the city's past, present and future, the Museum should be your first stop.
Coaching Financial Concepts
"Even the hall of famers have coaches"
As your local utility and an energy delivery company with more than a century of experience, our commitment to customer service, security, and satisfaction is guided by the progress of the past and the promise of the future.
Consolidated Printing
"America's Green Printer"
For over 35 years, Consolidated Printing Company has fused exceptional print quality with an insatiable commitment to environmental sustainability.
Court Theatre
Dr. Kiya C.A.R.E.S.
Dr. Kiya us a Licensed Clinical Professional Counselor, specalizing in marriage counseling and personal energy management.
Online: http://drkiya.com/
By Phone: 773.880.5492
DuPage County Democrats
CLICK HERE for details!
Going Green Limousine
Chicago's Ride Above The Rest!
Airport Transportation, Point to Point Transfers, and Charters available!
Local: (773) 295-5959
Toll Free: 1 (877) 844-1819
Goldberg Weisman Cairo
Personal Injury and Workers Compensation
One East Wacker Drive
38th and 39th Floors
Chicago, Illinois 60601-9654
toll-free (800) 486.1002
Guaranteed Rate Mortgage
Shimmy Braun and his team at Guaranteed Rate are respected by the real estate community for a high level of honesty, integrity and customer service.
Illinois Residential Mortgage Licensee
Hope for the Day
Utilizing Muisc and the Arts as a tool for suicide prevention.
Illinois Education Association
The Illinois Education Association-NEA's mission is to effect excellence and equity in public education and to be THE advocacy organization for all public education employees.
For a list of office locations, visit http://illinoiseducationassociation.org/contact-us/offices/ or call 1-800-252-8076
Innovative Insulations Solutions, Ltd.
At Innovative Insulation Solutions, Ltd., our mission is to deliver the highest performing foam insulation systems available on today's market. Our history of safe and effective application of these systems, coupled with total dedication to quality, consistently earns our customers' trust and satisfaction.
(847) 454-9081 www.GotFoamInsulation.com
Joffrey Ballet
Performances at the Auditorium Theatre – Chicago.
Tickets are available by visiting www.joffrey.org, www.ticketmaster.com, at the Auditorium Theatre Box Office, or by calling 312-386-8905.
The Kinderhook Tap
Kolateks Bakery & Deli
Chicago, IL 60707
(773) 637-3772
Korey Cotter Heather and Richardson
|Two First National Plaza
|20 South Clark Street
|Suite 500
|Chicago, Illinois 60603
|Telephone: 312.372.7075
Local 399 Operating Engineers
Local #11 Roofers Waterproofers and Allied Workers
Jobs done right the first time!!!
Mad as Hell Doctors
The Mad As Hell Doctors are not on the road these days but we are still part of Physicians for a National Health Program fighting for health care for all. Currently we are using this website only as an avenue for donations to support a 2013 nationwide radio 'Medicare for All' campaign streamed through Chicago's Progressive Talk.
Masters Transportation
2255 S. Throop Chicago, IL 60608 312-808-9700
"Driven by quality…Devoted to service."
At Masters Transportation "
It's All About YOU!"
Mephisto Great Lakes
Chicagoland's premier store for hand-crafted and premium, natural material shoes….from walking shoes to designer boots and everything in between; including BeautiFeel, Ugg, Mephisto, Dansko and Naot.
720-C Waukegan Rd
Deerfield, IL 60015
Natural Awakenings Magazine
Natural Awakenings is your guide to a healthier, higher quality and more balanced lifestyle.
PO Box 72Highland Park, IL, 60035
Norton's USA
400 Lageschulte St.
Barrington, Illinois 60010
The Place where EVERYTHING you buy is Made in the U.S.A.
NuMale Medical
Oak Park Jewelers
Your Diamond Store Since 1984!
101 S. Marion Street Oak Park, IL. 708-383-9695
Polaris Insurance Agency
(312)951-2606 x113
Radon Rulers
Visit RadonRulers.com and schedule your test today!
By Phone: (708) 715.1933
Ravinia Festival
Enjoy an evening under the stars at Ravinia Festival's 2014 season in Highland Park.
Visit www.ravinia.org for lawn & pavilion tickets, and information.
Rialto Square Theater
Celebrating 85 years!
15 E. Van Buren in Joliet Box Office – 815-726-6600
Check out our great line up of upcoming shows at www.rialtosquare.com
Tickets are also available at all Ticketmaster outlets.
Rush University Medical Center
To reach the hospital operator, please call (312) 942-5000.
To make an appointment with a doctor, call (888) 352-RUSH.
Rush University Medical Center
1653 W. Congress Parkway, Chicago, Illinois 60612
Second City Construction
Chicagoland's Home Improvement Experts since 1967!
Quality, Affordability, and Service is what we stand for.
If you think you might need a new roof, you probably do!
Call us for a free estimate at:
Stephen Goldstein
This book is a must-read for anyone who's sick and tired of the same old crap being spewed by today's politicians. It's witty, intelligent, and hilarious, an ideal gift for the progressives in your life.
StreetWise gives a hand-up to those who are homeless, or at risk of being homeless, by providing individuals who are willing to work, access to immediate employment and supportive social services. Every contribution helps.
Total Dentistry
Tub Hub and Tile
Visit our showroom at 3351 Dempster in Skokie
Or call for a free in-home estimate – 847-329-9600
United Auto Workers Region 4
680 Barclay Blvd.
(847) 459-3888
Viking Concrete Raising & Repair
Vince's Italian Resturant
Join us for lunch or dinner, and take 15% off your entire bill when you mention WCPT Radio! Come meet the world-famous Vince & enjoy authentic Italian food in a warm, friendly atmosphere.
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Call for reservations or free delivery at 847-991-7770
Winsol Power Company
Bringing you Tomorrow's energy today!
We are proud to provide our clients with the best products and services in the wind and solar industry!
Learn more at www.winsolpc.com


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Passing Lane Motors, LLC, St. Louis's Premier Classic Car Dealer, is pleased to present this 1971 Chevrolet SS Chevelle for sale! Highlights include: Real LS5, with... More
Clean Virginia car, beautiful Lemans blue paint, black SS striping, black vinyl interior, 396 ci engine, Edelbrock 4 bbl, aluminum intake, Hooker big tube... More
Clean original Georgia built car, Frame-Off Restoration, True (138) Super Sport car, beautiful Tuxedo black paint, black vinyl interior, 68' date coded 396 ci... More
BARN FIND FROM NORTH CAROLINA. 1968 CHEVROLET CHEVELLE CONVERTIBLE, MATCHING NUMBERS CODE EI 327-275HP V8, AUTOMATIC TRANSMISSION, POWER TOP, POWER STEERING, CLOCK, RADIO, RALLY WHEELS,... More
200 miles on Complete Frame-Off Restoration, True (138) Super Sport, beautiful factory (H) Willow Green metallic, factory black vinyl interior, black vinyl top, 67... More
Beautiful 1969 Chevrolet Chevelle Alot of work has been done to this car over the last few months. It has a Brand new 454 Engine... More
Stunning Nevada Silver '71 Chevelle Convertible! Fully restored and fitted with powerful LS6 crate motor and mated to an easy driving Automatic! The ultimate boulevard... More
For Sale 1970 Chevelle SS 396/402 Chevelle Engine: 1972 396/402 engine $38,900. TH400 Trans 3:73 posi rear 10 Bolt with 63K original miles Exterior Repaint... More
CHEVELLE 1971 SS454 CONVERTIBLE CLONE, strong 454cid, 4-speed, red with black striping, recent full service, see www.fraserdante.com for full inventory and information... More
396 malibu dressed up in SS attire looking good. SS badging around the car and a solid 396c.i. big block that give it the... More
Wow! Check out this big block Chevelle Convertible! Lot's of money spent on a balanced and blueprinted 402 cubic inch V8, fresh Turbo 400... More
1968 Chevrolet Chevelle 300 Coupe - 396 V8, 4-speed manual, power steering, power disc brakes, air conditioning, SS wheels, redline tires, 12-bolt positraction, AM/FM... More
Beautiful Garnet red paint, black SS striping, factory black vinyl interior, 69 date coded 396 ci engine, Muncie 4 speed manual transmission, Holley Performance... More
1970 Chevrolet Chevelle SS454 LS6. Frame-off restoration approx 2,000 miles ago. Two month old #58 Autumn Gold Base Coat / Clear Coat Acrylic Enamel Exterior Black Vinyl Interior Matching Number... More
1967 Chevrolet Chevelle convertible in red base coat/ clear coat. White convertible top and white interior. 454 big block with automatic transmission. Lots of high... More


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C.5 Bank Debits and Demand Deposits
This statistical release was published annually, with occasional cumulative issues. Data included covers bank debits or charges to demand deposit accounts.
Publication History:
1970-1976 Bank Debits and Demand Deposits (C.5)
1954-1969 Bank Debits to Demand Deposit Accounts Except Interbank and U.S. Government Accounts (C.5)
1946-1953 Bank Debits to Deposit Accounts Except Interbank Accounts (C.5)
1943-1945 Bank Debits to Deposit Accounts Except Interbank Accounts (FR 344)
1940-1942 Bank Debits: Debits to Deposit Accounts (FR 344)
1930-1939 Bank Debits: Debits to Individual Accounts (FR 344)
1919-1929 Debits to Individual Accounts
Board of Governors of the Federal Reserve System (U.S.), ([year]), C.5 Bank Debits and Demand Deposits, [issue title/date], accessed Sep 30, 2014 from FRASER, http:fraser.stlouisfed.org/publication/?pid=416
Related Publications:
- Bank Debits
- F.R. 578 Bank Debits -- Weekly Debits to Demand Deposit Accounts, Except Interbank and United States Government Accounts, of Weekly Reporting Member Banks in 101 Leading Cities
1920 to 1977


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We continue with our video tutorials series to help you work with our extensions effectively and with ease. Most of our Dreamweaver tools have a wide range of application and today we'll show you how to display a specific number of
random products in a section of your page, using HTML5 Data Bindings, DMXzone Database Connector PHP/ASP and also HTML5 Database Formatter.
Blog Posts
What You Missed This Week
Our weekly content summary
For those of you that couldn't follow us during the week on a daily basis, this is our weekly content summary, where you'll find all video tutorials, showcases and announcements that we made for the past five days. It features five super useful video tutorials that will teach you how to export dynamic HTML tables to PDF, show random products, store width and height of an image into a database and also how to validate if a record exists in a database. Check out the full list below and keep in ...
| HTML5 Data Bindings
Connect to your data
| HTML5 Data Bindings Formatter
Format your data any way you want
| DMXzone Database Connector ASP
Connect to your database
| DMXzone Database Connector PHP
Connect to your database


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(forgot?) or Register
The extension Avactis Shopping Cart Widget for WordPress allows you integrate your online store to your blog.
Download Version 1.5
Requires: 2.0.2 or higher
Compatible up to: 3.5.2
Last Updated: 2013-12-2
Downloads: 9,200
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text:
Primary Biliary Cirrhosis Center - Spring Valley, NV
WebMD Physician Directory
Spring Valley, Nevada
Primary Biliary Cirrhosis
What is PBC?
Primary biliary cirrhosis (PBC) is a chronic (long duration) disease characterized by progressive inflammation and destruction of the small bile ducts within the liver. What are the bile ducts...!--*ICCChunk-2908*-->
Other Related Primary Biliary Cirrhosis Articles
Emergency Contact for Spring Valley
Nearby Spring Valley Hospitals *
*Provider Directory Terms of Use:
The WebMD 'Provider Directory' is provided by WebMD for use by the general public as a quick reference of information about Providers. The Provider Directory is not intended as a tool for verifying the credentials, qualifications, or abilities of any Provider contained therein. Inclusion in the Provider Directory does not imply recommendation or endorsement nor does omission in the Provider Directory imply WebMD disapproval.


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Richard J. Greenstone practices copyright, trademark, licensing, and transactional law for the computer, entertainment, and publishing industries in San Francisco representing multimedia and online media companies, domain name owners, software, book and magazine publishers, programmers, authors, actors, artists, and producers throughout California, the United States, and the world. Richard Greenstone has over twenty nine years of legal experience in these industries and substantive law areas.
Richard Greenstone is a member of the California state bar, admitted to several United States District Courts, and is an elected member of the Los Angeles Copyright Society. Richard Greenstone practices before the United States Copyright Office and the United States Patent and Trademark Office in trademark matters. He has well over five hundred trademark applications and registrations to his credit performed for both clients and other attorneys who seek his advice. Richard has recently opened and is now developing a website, Trademarks All The Time, exclusively devoted to trademarks law, branding, registration, infringements, and trademark portfolio management.
Richard Greenstone also has an active entertainment law practice representing producers, directors, actors, authors, and musicians in the motion picture, television and music industries. His most current project involved clearance of all music rights for the album Welcome to the Folksong Café.
Richard Greenstone actively participates in the American Bar Association. He currently produces the program Young Lawyer and Law Student Orientation: Your Questions Answered for the American Bar Association's Forum on the Entertainment and Sports Industries. Richard served on the governing committee of the Forum and was also Division Chair for the Visual Arts Division, Publications Chair, and editor-in-chief of the Forum's law journal Entertainment and Sports Lawyer. Richard Greenstone also served as Forum liaison to the American Bar Association's Technology Counsel and was a member of the Standing Committee on Strategic Communications.
Richard Greenstone has authored over twenty articles on copyright, trademark, computer, entertainment, and licensing law, and has authored software on copyright law (17 U.S.C. § 101 et seq.) and the sale of fine prints (California Civil Code §§ 1740 - 1745.5). Richard Greenstone served on the advisory board and wrote a monthly column for Aspen Law and Business' magazine The Licensing Journal. Richard Greenstone also publishes Law Bytes. Currently in Law Bytes is an article by Bianca Francisco Hoogkamer and edited by Richard Greenstone on copyright protection for fashion designs.
Richard Greenstone is an avid photographer; his pictures appear on this website. In the past two years Richard displayed his work in two solo shows at Zindagi and McGuire galleries in San Francisco. You can see some of the pictures from these shows on his Facebook website Reflected Eye.
I invite you to call us to discuss your intellectual property and entertainment issues at (415) 438-1890.
While all of Richard Greenstone's photographs are original and created with great care, what you will not see on this website are pictures of models—like on large law firm web sites—acting as if they were attorneys. Our firm is the real thing with real vision and real legal experience and no stock photos!
Dry Standpipe by Richard Greenstone, 2004


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Matthew Strout MD, PhD
Assistant Professor of Medicine (Hematology) and Lecturer in Molecular Biophysics and Biochemistry
Research Interests
Cancer genetics; Lymphomagenesis; Leukemogenesis; Immune diversification; Epigenetics; Tissue banking; Targeted therapy
Current Projects
In order to cope with an unpredictable variety of invading antigenic insults, the humoral immune system is able to generate an enormously diverse antibody repertoire. This diversity is achieved through a complex series of molecular events that result in direct modification of Ig gene sequences with consequent changes in the specificity of the encoding antibodies. In the first step of immune diversification, variable (V), diversity (D), and joining (J) segments of the Ig genes are assembled in immature B cells by a site-specific reaction known as V(D)J recombination. This process occurs in the bone marrow early in B cell development and results in the production of a pool of mature B cells, each expressing a unique immunoglobulin B cell receptor.
Upon antigenic stimulation of mature B cells, germinal centers are formed where, in mice and humans, two additional DNA modification reactions serve to further diversify the immune response: somatic hypermutation (SHM) and class switch recombination (CSR). SHM introduces point mutations into the variable region of Ig heavy and light chain genes. This process underlies affinity maturation and results in the selection of a B cell that produces an antibody with high affinity for its target antigen. CSR is a deletion event that combines the variable region with different constant regions to result in the production of different immunoglobulin isotypes (IgG, IgE, or IgA). The enzyme activation induced cytidine deaminase (AID) is a cytidine deaminase that initiates these processes by introducing point mutations into the Ig variable regions (for SHM) and double-stranded DNA breaks into the Ig class switch regions (for CSR).
During the first phase of SHM and CSR, AID converts cytosine to uracil to result in a uracil-guanine (U-G) mismatch. Spontaneous U-G mismatches are normally corrected by high-fidelity base excision repair (BER) and mismatch repair (MMR) pathways. However, during the second phase of SHM and CSR, U-G mismatches are repaired by error-prone, low-fidelity BER and MMR pathways to yield mutations (for SHM) and DNA strand lesions (for CSR).
The intrinsic activity of AID is that of a DNA mutator and tight regulation is required to restrict this activity to the appropriate cell type and target loci in order to avoid mutations throughout the genome. However, aberrant targeting of AID activity contributes to translocations and point mutations of proto-oncogenes associated with many malignancies of B cell origin. Thus, the mechanisms that determine which genes will be targeted by AID and the factors that regulate how mutations are subsequently processed are of central importance to our understanding of the etiology of malignant transformation. Our lab currently has several projects underway that are directed at understanding the role of AID and associated factors in the pathogenesis of B cell malignancy:
1) The role of AID-associated DNA repair pathways in the pathogenesis of B cell lymphoma.
2) AID-induced epigenetic reprogramming in lymphoma through deamination of methylated CpG sites.
3) Somatic hypermutation of the mitochondrial genome by AID.
4) The role of AID in the pathogenesis of chronic lymphocytic leukemia.
5) Dysregulated expression of AID in acute lymphoblastic leukemia.
6) Regulation of the genotoxic threshold in B cells.
7) Differential targeting of the Ig loci for SHM versus CSR.
Research Summary
Antibodies are produced by the immune system's B cells and possess the ability to recognize and clear virtually any invading pathogen that the human body encounters. This is made possible by the enzyme activation induced cytidine deaminase (AID). The natural function of AID is to introduce mutations into genes that encode antibodies. The end result is production of an antibody with enhanced recognition of the invading pathogen. Under normal circumstances, AID should only mutate genes encoding antibodies. However, some B cell malignancies (non-Hodgkin lymphoma, multiple myeloma and chronic lymphocytic leukemia) harbor genetic mutations of non-antibody genes and there is evidence that AID causes these mutations. Research efforts in our lab are directed at:
- Establishing the role of AID in the pathogenesis of B cell malignancies;
- Characterizing AID-associated DNA repair pathways; and
- Identifying novel mechanisms of lymphomagenesis.