一段旅行,改變一個人的生活方式

"教育,是一段生命影響生命的歷程。"

   ※

每個期禱盼望,一個應許

願老天許妳

每場風雨過後,一道彩虹;
每滴淚水過後,一個微笑;
每個殷殷呵護,一個希望;
在人生每場戰役裡備受眷愛;
每道難題上門,一個忠實戰友相挺;
每次心痛嘆息,一首溫柔之歌為伴。


Two diseases with one hit: Inhibiting a potential obesity target to reduce cancer risk and to improve anti-cancer therapy

"I have got the offer from National University of Singapore, but I have not heard from any good news of US schools. I have attached what you want."



J Am Chem Soc.
 2010 Jan 20;132(2):656-66.

Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities.

Yang PYLiu KNgai MHLear MJWenk MRYao SQ.

Department of Chemistry, National University of Singapore, Singapore 117543.


"Hey.. the author list.. is your PhD advisor belong one of this team??"


 
"How did you find this paper? Yao will be my PhD supervisor."


   ※ 



I found this paper because of our CB1 & CXCR4 projects, and because of my mentor Prof. Dr. Paul MacLean's research directions.


http://www.uchsc.edu/sm/endo/maclean.php
  
My mentor is an amazing Physiologist, an expert in Metabolism field. As all DBPR members know CB1 project is one of the project belong to the anti-diabetic filed, CXCR4 is an anti-cancer project..

As you know, I participated a wonderful conference in Aug 2009. Paul is the conference chair-person..
One of Paul's collaborators in UCDenver is an expert in the Warburg effect.
http://www.uchsc.edu/pathology/research/anderson_research.html
 
http://www.asbmb.org/News.aspx?id=1972&catId=192

JLR: NEARLY A CENTURY LATER, NEW FINDINGS SUPPORT WARBURG THEORY OF CANCER

Cause "cancer cell has different metabolism phenotype", using Metabolism this concept, we can imagine and realize that PI3K and Akt these signaling kinases involved in cell survival and proliferation. Recent evidence also suggests that PI3K/Akt activates the SREBPs, master transcriptional regulators of lipid metabolism. Explore the various mechanistic links between Akt and SREBP can let us consider this relationship in diseases where Akt and lipids play crucial roles, including diabetes, viral infections and cancer. DBPR has anti-diabetes / anti-virus / anti-cancer projects, thanks for Paul let us all realize the power of Metabolism


This is the first paper I know Dr. Steven Anderson-
11. C.D. Young and S.M. Anderson, 2008.  “Sugar and fat-that’s where it is at: metabolic changes in tumors.” Breast Cancer Research, 10(1): 202.


Then I gave this article to Paul.

Metabolic Targeting of Cancers: From Molecular Mechanisms to Therapeutic Strategies. Current Medicinal Chemistry, 2009, 16, 1561-1587 (as attachment)

Table 1. Targets and Related Therapies in the Energy Metabolic Pathway for Antitumor Treatment
P.1579  Inhibition of GLUT 1
P.1580  Inhibition of Fatty Acid Synthase (C75 & Orlistat)
P.1581  Activation of AMPK, thus inhibiting mTOR and fatty acid synthesis (Metformin) 


Faculty of 1000 Biology: evaluations for Yang PY et al J Am Chem Soc 2010 Jan 20 132 (2) :656-66 

J Am Chem Soc
 2010 Jan 20 132(2):656-66 
Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities.
Yang PY, Liu K, Ngai MH, Lear MJ, Wenk MR, Yao SQ

Activity-based profiling of small molecule-protein interactions is useful for unbiased, empirical identification of off-targets of development-stage or even marketed drugs. This pioneering paper describes a singular method in which the addition of an alkyne to the drug permits target isolation using click chemistry. 
A critical step in drug development is the identification of off-target activities. Profiling drug candidates against large panels of targets for other known drugs is often used for this purpose, but such methods cannot find off-target activities versus proteins for which assays have not been established. Tetrahydrolipstatin is a natural product-derived drug that is a lipase inhibitor used against obesity that may also be useful in cancer. Its action is based on acylation of active-site nucleophiles by its beta-lactone unit. Analogs were prepared by the almost imperceptible replacement of a terminal ethyl group by an ethynyl group, assuring one that the targets identified are highly likely to be the same as for the native agent. They include HSP90 and three ribosomal proteins. A limitation of the method as described is that not all drug candidates covalently bind to their targets. Here, identification of off-target activities may have also been less vital since tetrahydrolipstatin is already marketed for a condition much less severe than cancer. However, only a few other methods (such as phage display cloning) can empirically examine the interactions of a candidate with all of the targets in the proteome. 


http://pipeline.corante.com/
archives/cancer/
MAGL: A New Cancer Target


That's the world Paul let me see and understand. 

I'm glad have a medicinal chemistry PhD friend also interested in Fatty Acid filed.
Best of luck to all your future endeavors!!!!!!


   ※ 



Breast Cancer Res Treat.

 2010 Feb;120(1):253-60. Epub 2009 Jun 19.

Reversal of the glycolytic phenotype by dichloroacetate inhibits metastatic breast cancer cell growth in vitro and in vivo.

Sun RCFadia MDahlstrom JEParish CRBoard PGBlackburn AC.

Molecular Genetics Group, John Curtin School of Medical Research, Australian National University, P.O. Box 334, Canberra, 2601, Australia.


Fig. 3 In vivo studies. a) Rat lungs showing the metastases formed in control and b) high dose DCA-treated.

Breast Cancer Res Treat


The glycolytic phenotype is a widespread phenomenon in solid cancer forms, including breast cancer. Dichloroacetate (DCA) has recently been proposed as a novel and relatively non-toxic anti-cancer agent that can reverse the glycolytic phenotype in cancer cells through the inhibition of pyruvate dehydrogenase kinase. We have examined the effect of DCA against breast cancer cells, including in a highly metastatic in vivo model. The growth of several breast cancer cell lines was found to be inhibited by DCA in vitro. Further examination of 13762 MAT rat mammary adenocarcinoma cells found that reversal of the glycolytic phenotype by DCA correlated with the inhibition of proliferation without any increase in cell death. This was despite a small but significant increase in caspase 3/7 activity, which may sensitize cancer cells to other apoptotic triggers. In vivo, DCA caused a 58% reduction in the number of lung metastases observed macroscopically after injection of 13762 MAT cells into the tail vein of rats (P = 0.0001, n > or = 9 per group). These results demonstrate that DCA has anti-proliferative properties in addition to pro-apoptotic properties, and can be effective against highly metastatic disease in vivo, highlighting its potential for clinical use. 


It's not only theory or hypothesis, it's true. That's the reason I told you I'm really grateful the world Paul gave me showed me and shared with me. 

It's Paul let me have solid faith that Physiology is powerful in Drug Discovery.


Target inflammation to ease Obesity Ills


Symposium topics:
  • Inflammation in autoimmunity
  • Inflammation in infectious disease
  • Inflammation in metabolic disease
  • Inflammation in cancer
  • Inflammation in the nervous system

&

 http://www.uch.edu/conditions/diabetes-endocrine/index.aspx

Treating Diabetes & Endocrine Conditions
at University of Colorado Hospital

With care recognized again in 2008 by U.S. News & World Report as one of the best not just in the region, but in the country for treating hormonal disorders.

Collaborative care

Request an appointment at UCH

Go to our Request an Appointment page

We are in fact proud of the elite, collaborative care we bring to patients every day. Leading endocrinologists, nurses and caregivers from a broad spectrum of related specialties come together to consider patients from angles not viewed at many health care facilities.

They are backed by a long history of being among the first to bring new treatments to these complex conditions. In advancing diabetes care, for example, this is the place that:

  • Discovered the diabetes-related molecule that identifies if a person will develop juvenile diabetes.
  • Discovered the single insulin gene that is crucial in the development of childhood, or Type 1, autoimmune diabetes in lab mice.

http://www.uch.edu/conditions/weight-metabolism/index.aspx

Weight and Metabolism: Conditions Treated atUniversity of Colorado Hospital

University  of Colorado Hospital specializes in the following weight and metabolism related conditions:

Featured Doctors

Dr. Jonathan Schoen is a board-certified bariatric surgeon. He has extensive experience performing laparoscopic and traditional weight loss surgery.

Dr. Robert Eckel is a board-certified endocrinologist who is a past President of the American Heart Association.




Current Issue

Featured articles (free):

Special feature: Type 1 diabetes

An in-depth look at the immunological basis of type I diabetes with
• an overview by Santamaria
• a perspective on autoantigens by Standinsky, Kappler, and Eisenbarth

And reviews on
• the genetic architecture by Todd
• the prediction modalities by Ziegler and Nepom
• autoimmune polyendocrine syndromes byHusebye and Anderson
• immunotherapy by Luo, Herold, and Miller


Next issue: May 28, 2010



   ※ 


Switching fat from the periphery to bone marrow: why in Type I diabetes? Expert Review of Endocrinology & Metabolism, May 2009, Vol. 4, No. 3, Pages 203-207.

&

Endocannabinoids, FOXO and the metabolic syndrome: Redox, function and tipping point - The view from two systems. Immunobiology. 2009 May 18.


Fig. 1. Integrating the ECS with key transcriptional factors. Green boxes and arrows represent known and possible ECS functions and modulation pathways.


Fig. 2. The ECS as an endohormetic signalling system.


Fig. 3. Thrifty inflammatory tipping point and metabolic syndrome.


Fig. 4. The origins of the metabolic syndrome: the ECS and thrifty-inflammatory tipping point.

&

http://www.signaling-gateway.org/update/updates/200909/nri2630.html
Inflammation: Finding the T in fat

http://www.nature.com/nrd/journal/v8/n9/full/nrd2978.html

Research Highlight

Nature Reviews Drug Discovery 8699 (September 2009) | doi:10.1038/nrd2978

Metabolic disorders: Finding the T in fat


ORIGINAL RESEARCH PAPERS
  1. Nishimura, S. et alCD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesityNature Med. 15, 914–920 (2009Article

  2. Winer, S. et alNormalization of obesity-associated insulin resistance through immunotherapyNature Med. 15, 921–929 (2009Article
  3. Feuerer, M. et alLean, but not obese, fat is enriched for a unique population of regulatory T cells that affect metabolic parameters. Nature Med. 15, 930–939 (2009Article ← "To our surprise, more than half of the CD4+ T cells expressed Foxp3 (Fig. 1a), a much higher fraction than that normally found in lymphoid (for example, in the spleen or lymph nodes) or nonlymphoid (for example, lung or liver) tissues (Fig. 1b), including in subcutaneous fat (Fig. 1c)."

FURTHER READING
  1. Lumeng, C. N., Maillard, I. & Saltiel, A. R. T-ing up inflammation in fat. Nature Med. 15, 846–847 (2009Article




Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul. 2009 Oct;43(4):157-68.

Leptin and Adiponectin: new players in the field of tumor cell and leukocyte migration. Cell Commun Signal. 2009 Dec 23;7:27.

Leptin: a critical regulator of CD4+ T-cell polarization in vitro and in vivo. Endocrinology. 2010 Jan;151(1):56-62. Epub 2009 Dec 4.



http://abcnews.go.com/Business/wireStory?id=9980238
Hot tip: Target inflammation to ease obesity ills (Mar 1, 2010)

WASHINGTON ─ What if you could be fat but avoid heart disease or diabetes? Scientists trying to break the fat-and-disease link increasingly say inflammation is the key. In the quest to prove it, a major study is under way testing whether an anti-inflammatory drug - an old, cheap cousin of aspirin - can fight the Type 2 diabetes spurred by obesity. And intriguing new research illustrates how those...

Watch this in YouTube →
http://tinyurl.com/2cyow5s




Gene expression profiles for the human pancreas and purified islets in type 1 diabetes: new findings at clinical onset and in long-standing diabetes. Clin Exp Immunol. 2010 Jan;159(1):23-44.

" Changes in gene expression in islets were confined mainly to endocrine and neural genes, some of which are T1D autoantigens. By contrast, these islets showed only a few overexpressed immune system genes, among which bioinformatic analysis pointed to chemokine (C-C motif) receptor 5 (CCR5) and chemokine (CXC motif) receptor 4) (CXCR4) chemokine pathway activation. Remarkably, the expression of genes of innate immunity, complement, chemokines, immunoglobulin and regeneration genes was maintained or even increased in the long-standing cases. Transcriptomic data favour the view that T1D is caused by a chronic inflammatory process with a strong participation of innate immunity that progresses in spite of the regulatory and regenerative mechanisms."



[CXCR4 ─ Metabolism]

Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg. 2008;70(3):193-219. (← Language: Dutch )

Inhibition of gluconeogenesis in primary hepatocytes by stromal cell-derived factor-1 (SDF-1) through a c-Src/Akt-dependent signaling pathway. J Biol Chem. 2008 Nov 7;283(45):30642-9.

The SDF-1alpha/CXCR4 axis induces the expression of fatty acid synthase via sterol regulatory element-binding protein-1 activation in cancer cells. Carcinogenesis. 2010 Apr;31(4):679-86.

&

[CCR5 ─ Atherosclerosis] 

CC chemokine receptor 5 influences late-stage atherosclerosis. Atherosclerosis. 2007 Nov;195(1):e92-103.

A CCR2/CCR5 antagonist attenuates an increase in angiotensin II-induced CD11b+ monocytes from atherogenic ApoE-/- mice. Cardiovasc Drugs Ther. 2009 Apr;23(2):113-20. (Pfizer) 



NIH encourages translational collaboration with INDUSTRY.

20071114012918.jpg


How to improve R&D productivity: the pharmaceutical industry's grand challenge.
Nat Rev Drug Discov. 2010 Mar;9(3):203-14. (Eli Lilly)

NIH encourages translational collaboration with industry. Nat Rev Drug Discov. 2010 Apr;9(4):255-6.

What health reform means for innovation. Nat Biotechnol. 2010 Apr;28(4):293.




Depression-like phenotype following chronic CB(1) receptor antagonism. Neurobiol Dis. 2010 Apr 8.  (Pfizer)

Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov. 2010 May;9(5):387-98. (Eli Lilly)


&

Chi-Liang Eric Yen, University of Wisconsin-Madison #17
“Triacylglycerol synthesis enzymes and energy balance.”


Prof. Dr. Chi-Liang Eric Yen
http://www.nutrisci.wisc.edu/FACULTYPAGES/f_yen.html

http://tinyurl.com/ddmd6u
Stopping Food Fat from Becoming Body Fat – A New Drug Target (April 1, 2009)

"That work now has led to the first phase of human clinical trials to test a weight control drug that targets DGAT."

[then...]

In vivo efficacy of acyl CoA: Diacylglycerol acyltransferase (DGAT) 1 inhibition in rodent models of postprandial hyperlipidemia. Eur J Pharmacol. 2010 Apr 10. (Abbott)

Inhibitors of diacylglycerol acyltransferase: a review of 2008 patents. Expert Opin Ther Pat. 2010 Jan;20(1):19-29. (Abbott)

[then...]

Novel acyl coenzyme A: diacylglycerol acyltransferase 1 inhibitors-synthesis and biological activities of N-(substituted heteroaryl)-4-(substituted phenyl)-4-oxobutanamides. Chem Pharm Bull (Tokyo). 2010;58(5):673-9. (Takeda)

Novel acyl coenzyme A (CoA): diacylglycerol acyltransferase-1 inhibitors: synthesis and biological activities of diacylethylenediamine derivatives. Bioorg Med Chem. 2010 Apr 1;18(7):2785-95. (Takeda)


&

http://tinyurl.com/y4ewb5c
A Landmark In Clinical Trial Data Interpretation. (Apr 16, 2010 by Dr. Derek Lowe)

http://tinyurl.com/26pb9or
Open Access Drug Target Database Launched. (Apr 19, 2010 from Drug Discovery Opinion)


&

http://tinyurl.com/y5vburm
Capturing the big picture of the 2010 Annual AACR tweetsLIVE is better!! (Apr 22, 2010 from Pharma Strategy Blog


&

http://www.the-aps.org/meetings/eb10/abs/sebm-mulroney.htm (APS)
http://www.sebm.org/announcements.htm (SEBM)

Evolving from Reductionism to Holism: The Future is Systems Medicine
Sponsored by the Society for Experimental Biology and Medicine
Systems Biology (-omics) and Translational Physiology Tracks


Sunday, April 25 � 3:15 PM-5:30 PM
Anaheim Convention Center, Ballroom B

Chaired:
Susan E. Mulroney, Georgetown Univ. Med. Ctr.
Howard Federoff, Georgetown Univ. Med. Ctr.


Institute for Systems Biology announced the collaboration with the American Physiological Society at EB#10.



Current issue


Focus

The Predictive Safety Testing Consortium


This focus presents the first formal results of the Predictive Testing Safety Consortium, a community-wide effort involving industry, non-profit institutions and regulators to qualify seven nephrotoxicity biomarkers in the preclinical and ultimately clinical settings. In gathering and analyzing these data, the consortium has taken the first steps in outlining a generic path for regulatory qualification of biomarkers in general.

Editorial

Focus on The Predictive Safety Testing Consortium

Biomarkers on a roll p431

doi:10.1038/nbt0510-431

A consortium of industry, nonprofit institutions and regulators outlines a rolling biomarker qualification process, providing the first clear path for translation of such markers from discovery to preclinical and clinical practice.




Research at the interface of industry, academia and regulatory science. Nat Biotechnol. 2010 May;28(5):432-3.

Next-generation biomarkers for detecting kidney toxicity. Nat Biotechnol. 2010 May;28(5):436-40.

Evolution of biomarker qualification at the health authorities. Nat Biotechnol. 2010 May;28(5):441-3.

A roadmap for biomarker qualification. Nat Biotechnol. 2010 May;28(5):444-5.

Towards consensus practices to qualify safety biomarkers for use in early drug development. Nat Biotechnol. 2010 May;28(5):446-54. (Merck)

Renal biomarker qualification submission: a dialog between the FDA-EMEA and Predictive Safety Testing Consortium. Nat Biotechnol. 2010 May;28(5):455-62. (Novartis)

Urinary clusterin, cystatin C, beta2-microglobulin and total protein as markers to detect drug-induced kidney injury. Nat Biotechnol. 2010 May;28(5):463-9. (Novartis)

Urinary biomarkers trefoil factor 3 and albumin enable early detection of kidney tubular injury. Nat Biotechnol. 2010 May;28(5):470-7. (Merck)

Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol. 2010 May;28(5):478-85. (Harvard Medical School)

A panel of urinary biomarkers to monitor reversibility of renal injury and a serum marker with improved potential to assess renal function. Nat Biotechnol. 2010 May;28(5):486-94. (Merck)


The Adiponectin-Mitochondria Connection

Steven Smith, Pennington Biomedical Research Center#29
“Unlocking the “combination” to more effective pharmacotherapy.”



+

Paul MacLean, University of Colorado Denver #19
“Countering the biological adaptations to weight reduction with exercise.”



+

Ronald Cortright, East Carolina University #5
“Skeletal Muscle Mitochondrial Function and Lipid Metabolism in Obese African-American and Caucasian Women.”




Diet, energy metabolism and mitochondrial biogenesis. Curr Opin Clin Nutr Metab Care. 2007 Nov;10(6):679-87. (PBRC)



Transcriptional control of mitochondrial biogenesis and function. Annu Rev Physiol. 2009;71:177-203.

The transcriptional network that controls mitochondrial gene expression.


Positive and negative signals that regulate mitochondrial biogenesis and converge at the PGC-1α promoter and/or the PGC-1α protein.


Diverse physiological signals regulate mitochondrial biogenesis in a tissue-specific manner.




The mitochondrial rhomboid protease PSARL is a new candidate gene for type 2 diabetes. Diabetologia. 2005 Mar;48(3):459-68.

Genetic variation in PARL influences mitochondrial content. Hum Genet. 2010 Feb;127(2):183-90.

&

Skeletal muscle glucose uptake during exercise: a focus on reactive oxygen species and nitric oxide signaling. IUBMB Life. 2009 May;61(5):479-84.




CaMKK is an upstream signal of AMP-activated protein kinase in regulation of substrate metabolism in contracting skeletal muscle. Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1724-32.

Exercise-induced histone modifications in human skeletal muscle. J Physiol. 2009 Dec 15;587(Pt 24):5951-8.

Exercise-induced histone acetylation - playing tag with the genome. J Physiol. 2010 Mar 15;588(Pt 6):905-6.

Histone modifications and skeletal muscle metabolic gene expression. Clin Exp Pharmacol Physiol. 2010 Mar;37(3):392-6.

+





Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010 Apr 29;464(7293):1313-9.

The Adiponectin-Mitochondria Connection [
http://tinyurl.com/23cbjvq]

&

Regulation of skeletal muscle oxidative capacity and insulin signaling by the mitochondrial rhomboid protease PARL. Cell Metab. 2010 May 5;11(5):412-26.

http://tinyurl.com/267yshb (Flash ← can't hear the voice???)
http://tinyurl.com/3amvcvr (Slide)


Congrats to Prof. Dr. Paul MacLean, congrats to Dr. Steven Smith!! 


&


Wu, M et al. (2007). Multiparameter metabolic analysis reveals a close link between attenuated mitochondrial bioenergetic function and enhanced glycolysis dependency in human tumor cells. Am J Physiol Cell Physiol 292:C125-C136

Sridharan, V et al. (2007). The prolyl hydroxylase oxygen-sensing pathway is cytoprotective and allows maintenance of mitochondrial membrane potential during metabolic inhibition. Am J Physiol Cell Physiol 292:C719-C728.


&

http://www.the-aps.org/publications/specialcalls/regu.htm#mitochondrial

Special Calls for Papers
American Journal of Physiology - Regulatory, Integrative and Comparative Physiology


Mitochondrial Function/Dysfunction in Health and Disease

Submission deadline: December 31, 2010


&


http://www.circuitblue.com/mito/
Finding A Cure for Mitochondrial Diseases

http://www.biologicalgerontology.com/mito.shtml
Mitochondria and Aging


[Cell Metabolism] May 2010's Featured Reviews: Focus on Brown Adipocytes

http://tinyurl.com/ykqntcj
The Top 10 Everything of 2009
TIME charts the highs and lows of the past year in 50 wide-ranging lists

Top 10 Medical Breakthroughs
10. Brown Fat in Adults




Why the Physiology textbook tell us WAT for storage energy, BAT for thermogenesis?

If they are all "adipose tissue", why they behaved so different (← one for storage fat, one for burn fat??)




Promoter traps in embryonic stem cells: a genetic screen to identify and mutate developmental genes in mice. Genes Dev. 1991 Sep;5(9):1513-23.

→ I like these two great pictures-
Spatial patterns of expression resulting from promoter trap events. Embryos from different strains and stages were stained with X-gal to reveal B-gal activity. Thus we can see the promoter expression in every stages in mouse prenatal development.



Brown adipose tissue: function and physiological significance. Physiol Rev. 2004 Jan;84(1):277-359.


→ Prof. Dr. Barbara Cannon is very famous in Lipids filed. I like this BAT review paper very much!!


In 2007, Prof. Dr. Barbara Cannon had an invited review published in Am J Physiol Endocrinol Metab.


→ To see the PET demo, click this link:
http://www.med.harvard.edu/JPNM/chetan/normals/brown_fat/case.html

&

Molecular determinants of brown adipocyte formation and function. Genes Dev. 2008 May 15;22(10):1269-75.

Regulation of the brown and white fat gene programs through a PRDM16/CtBP transcriptional complex. Genes Dev. 2008 May 15;22(10):1397-409.

PRDM16 controls a brown fat/skeletal muscle switch. Nature. 2008 Aug 21;454(7207):961-7.



finally..

Developmental biology: Neither fat nor flesh. Nature. 2008 Aug 21;454(7207):947-8.


"In mammals, white adipose tissue stores fat, whereas brown adipose tissue burns fat. Brown adipocytes have a common origin with muscle cells, which could help explain their unusual function."




http://www.the-aps.org/meetings/eb10/abs/ceps-sweazea.htm

Comparative Metabolic Physiology
Sponsored by the APS Animal Care Committee
Hypoxia and Oxidative Stress and Thermoregulation and Environmental Stress Tracks


Tuesday, April 27 � 3:15 PM-5:45 PM
Anaheim Convention Center, Room 303D

Chaired:
Karen Sweazea, Arizona State Univ.





Cell Metabolism

Volume 11, Issue 5: May 5, 2010
Next issue: June 9, 2010

Featured Reviews  free

Focus on Brown Adipocytes

Editorial

Brown Adipocyte Focus

Emambokus and Wang

Minireviews

Human Brown Adipose Tissue
Enerbäck
Distribution and Development of Brown Adipocytes in the Murine and Human Adipose Organ
Frontini and Cinti
Transcriptional Control of Brown Fat Development
Kajimura et al.
Brown Fat and the Myth of Diet-Induced Thermogenesis
Kozak
The Changed Metabolic World with Human Brown Adipose Tissue: Therapeutic Visions
Nedergaard and Cannon

GRE Vocabulary ─ The exact meaning of the word "Educate"

comes from the root word "educe".
It means, to bring forth what is within, to bring out potential.


   ※ 


From Metabolism to Inflammation, thanks a lot for Eric shared his world his relationship at Academic Sinica with me, and glad Dr. Robert Eckel is such a kindly and influential Endocrinologist;

From Metabolism to Oncology, appreciated
Dr. Ronald Cortright not only changed his presentation direction but also have a Taiwanese student in his lab, appreciated speakers from UCDenver were all so kind-hearted and so warm.


From Peripheral to CNS, Dr. Deborah Clegg / Dr. Barry Levin / Dr. Hans-Rudolf Berthoud / Dr. Karen Teff / Dr. Jeffry Zigman / Dr. Philip Larsen / Dr. Kevin Grove / Dr. Jose Fernandez / Dr. Philip Scarpace & Dr. Yi Zhang ← This world is.. very impressed.

GENETIC STUDY??? What's the true meaning of this?? ← Dr. Wendy Johnson-Askew, Dr. Frederique Tesson & Dr. Anthony Comuzzie!!!

Liver is a good Target ─ Dr. Sam Klein, Dr. Alessandro Pocai.

Good Clinical Practices ─ Dr. John Blundell, Dr. Steve Smith, and Dr. Camilla Pedersen!!

Master is the one who can point out the meaning, the contribution, and the future immediately ─ Those brilliant comments from Dr. Hans-Rudolf Berthoud and Dr. John Blundell.. that's the best demonstrate about the power of the Expert to a green hand. Science is the progress of "Understand the MEANING and know what's the NEXT STEP".


   ※ 


I really like FASEB SRC. It remind what I have learned in the college biology classroom- 

Expectations for Biology Majors
1) Ability to express yourself clearly to others; 
2) Ability to synthesize from pieces of facts into a coherent idea; 
3) Ability to find, store, and retrieve information; 
4) Humanity: to be empathy for men and nature.



The power of the Publisher: We make the TREND

http://www.the-aps.org/meetings/eb10/abs/ceps-sweazea.htm
Comparative Metabolic Physiology
Sponsored by the APS Animal Care Committee
Hypoxia and Oxidative Stress and Thermoregulation and Environmental Stress Tracks


Tuesday, April 27 � 3:15 PM-5:45 PM
Anaheim Convention Center, Room 303D

Chaired:
Karen Sweazea, Arizona State Univ.

3:15 PM
The Fats of Being Cold: Biological Membranes and Antioxidant Activity.
Elizabeth Crockett, Ohio Univ.


"It can truly be said of living cells, that by their membranes ye shall know them." ─ Davson & Danielli, 1952



[about NPG]

http://www.nature.com/press_releases/win.html
Nature Publishing Group partners with Worldwide Innovative Networking (WIN) in Personalized Cancer Medicine

http://tinyurl.com/3xslcjt
Nature Lipidomics Gateway




http://www.the-aps.org/meetings/eb10/abs/tpg-basavappa.htm
Integrins: New Insights and Therapeutic Targets
Sponsored by the APS Translational Physiology Group and Liaison with Industry Committee
Systems Biology (-omics) Track


Wednesday, April 28 ?8:00 AM-10:00 AM
Anaheim Convention Center, Ballroom C

Chaired:
Shaila Basavappa, Takeda Pharmaceutical International
Gordon MacGregor, Salix Pharmaceuticals, Inc.




Integrase inhibitor, CCR5 antagonist, fusion inhibitor. Nippon Rinsho. 2010 Mar;68(3):520-4. (AIDS Clinical Center, International Medical Center of Japan. Article in Japanese)

A CCR2/CCR5 antagonist attenuates an increase in angiotensin II-induced CD11b+ monocytes from atherogenic ApoE-/- mice. Cardiovasc Drugs Ther. 2009 Apr;23(2):113-20. (Pfizer)

&

Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer? PLoS One. 2010 Apr 8;5(4):e10087.

Upregulation of CXCR4 favoring neural-like cells migration via AKT activation. Neurosci Res. 2010 Apr 20.



http://www.the-aps.org/meetings/aps/inflammation/
2010 APS Conference: Inflammation, Immunity and Cardiovascular Disease

[APS 2010] Inflamation

Dates: August 25-28
Westin Westminster, Colorado 




http://www.lipidmaps.org/update/2010/100501/update.html

Lipidomics update - May 2010


Phospholipids: Key Players in Apoptosis and Immune Regulation

Chaurio R., Janko C., Muñoz L., Frey B., Herrmann M. et al.

Molecules 14, 4892 - 4914 (2009)

[doi: 10.3390/molecules14124892]

Induction of fatty acid synthesis is a key requirement for phagocytic differentiation of human monocytes

Ecker J., Liebisch G., Englmaier M., Grandl M., Robenek H. et al.

Proceedings of the National Academy of Sciences (Published online 27 April 2010)

HIV-protease inhibitors suppress skeletal muscle fatty acid oxidation by reducing CD36 and CPT1 fatty acid transporters

Richmond S., Carper M., Lei X., Zhang S., Yarasheski K. et al.

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 1801, 559 - 566 (2010)

[doi: 10.1016/j.bbalip.2010.01.007]



Current Opinion in HIV and AIDS:
March 2009 - Volume 4 - Issue 2 - p 96-103
doi: 10.1097/COH.0b013e328324bbec
Entry inhibitors: Edited by Jose A. Este

The biology of CCR5 and CXCR4

Alkhatib, Ghalib




Selzentry (maraviroc) is a CCR5 co-receptor antagonist in antiretroviral therapy field (Pfizer) 

&

www.nih.gov
A large genetic study has identified 3 new genes associated with the blinding eye disease age-related macular degeneration. Two of the genes are involved in the cholesterol pathwaya formerly unknown biological pathway for development of the disease.
4月20日 3:28 ·  ·  · 分享
Wan-Ling Chung
Wan-Ling Chung 
I like this article very much!!!!! *^__________^*

Localisation of SDF-1 and its receptor CXCR4 in retina and choroid of aged human eyes and in eyes with age related macular degeneration. Br J Ophthalmol. 2006 Jul;90(7):906-10. 

Relations between metabolic syndrome, oxidative stress and inflammation and cardiovascular disease. Verh K Acad Geneeskd Belg. 2008;70(3):193-219. ← The 1st article about CXCR4 and metabolic syndrome I have found (the small problem is.. Language: Dutch)

Inhibition of gluconeogenesis in primary hepatocytes by stromal cell-derived factor-1 (SDF-1) through a c-Src/Akt-dependent signaling pathway. J Biol Chem. 2008 Nov 7;283(45):30642-9.

Elevated insulin secretion from liver X receptor-activated pancreatic beta-cells involves increased de novo lipid synthesis and triacylglyceride turnover. Endocrinology. 2009 Jun;150(6):2637-45.

The SDF-1alpha/CXCR4 axis induces the expression of fatty acid synthase via sterol regulatory element-binding protein-1 activation in cancer cells. Carcinogenesis. 2010 Apr;31(4):679-86.
4月20日 13:53 · 


All that being said, believe 2010 APS Conference: Inflammation, Immunity and Cardiovascular Disease will be another meaningful conference!! 


Exercise Physiology:Rethink the way you treat Schizophrenia & Alzheimer's disease

WebMD.jpg


"obesity ─ lipids / cell membrane ─ cancer (peripheral) or Alzheimer's disease (central)"



Role of exercise-induced brain-derived neurotrophic factor production in the regulation of energy homeostasis in mammals. Exp Physiol. 2009 Dec;94(12):1153-60. [The Physiological Society (UK)]

Increased food intake leads to obesity and insulin resistance in the tg2576 Alzheimer's disease mouse model. Endocrinology. 2010 Apr;151(4):1532-40.



Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase. Diabetologia. 2009 Jul;52(7):1409-18.



http://tinyurl.com/26bkozv
Medscape Medical News (May 12, 2010)
Exercise Beneficial for Physical and Mental Health Outcomes in Schizophrenia



http://emedicine.medscape.com/article/88484-overview
eMedicine Specialties > Sports Medicine > Introductory Topics in Sports Medicine
Exercise Physiology

&




Physical activity and lipid oxidation. Apunts Med Esport. 2010;45(165):30-39

The diseasome of physical inactivity--and the role of myokines in muscle ─ fat cross talk. J Physiol. 2009 Dec 1;587(Pt 23):5559-68. [The Physiological Society, Symposium Review]



http://www.apps.org.au/Proceedings/40/11-16/
PGC-1α in muscle links metabolism to inflammation [Australian Physiological Society]



The role of exercise and PGC1alpha in inflammation and chronic disease. Nature. 2008 Jul 24;454(7203):463-9.

PGC-1alpha in aging and anti-aging interventions. Biochim Biophys Acta. 2009 Oct;1790(10):1059-66.

PGC-1alpha and Myokines in the Aging Muscle - A Mini-Review. Gerontology. 2010 Feb 4.

The role of exercise-induced myokines in muscle homeostasis and the defense against chronic diseases. J Biomed Biotechnol. 2010;2010:520258.



The impact of dietary energy intake on cognitive aging. Frontiers in Aging Neuroscience March 2010 [NIA]

Rodents that are insulin resistant and obese as the result of genetic factors, overeating and/or a sedentary lifestyle, exhibit cognitive defi cits that worsen with advancing age compared to their more svelte counterparts. Data from epidemiological and clinical studies suggest similar adverse effects of excessive dietary energy intake and insulin resistance on cognition in humans. Our fi ndings from studies of animal models suggest that dietary energy restriction can enhance neural plasticity and reduce the vulnerability of the brain to age-related dysfunction and disease. Dietary energy restriction may exert benefi cial effects on the brain by engaging adaptive cellular stress response pathways resulting in the up-regulation of genes that encode proteins that promote neural plasticity and cell survival (e.g., neurotrophic factors, protein chaperones and redox enzymes). Two energy state-sensitive factors that are proving particularly important in regulating energy balance and improving/preserving cognitive function are brain-derived neurotrophic factor and glucagon-like peptide 1. Alternate day calorie restriction, novel insulin-sensitizing and neuroprotective agents, and drugs that activate adaptive stress response pathways, are examples of approaches for preserving cognitive function that show promise in preclinical studies.


Obesity ─ Lipids / Cell membrane ─ Cancer (peripheral) or Alzheimer's disease (central)

Institute of Molecular Biology, Academia Sinica Seminar:

Dr. Joseph P. Yuan
(Department of Physiology, University of Texas Southwestern Medical Center)

Mar.16. 10:00AM , IMB 1F Auditorium

"Regulation of TRPC and Orai Ca2+ Influx Channels by STIM1"

&

Dr. Ding Xue
(Department of Molecular, Cellular & Developmental Biology, University of Colorado at Boulder )

Mar.23. 11:00AM , IMB 1F Auditorium

"Programmed Cell Death and Lipid Asymmetry in C. elegans"



Regulation of CXCR4 receptor dimerization by the chemokine SDF-1alpha and the HIV-1 coat protein gp120: a fluorescence resonance energy transfer (FRET) study. J Pharmacol Exp Ther. 2004 Jul;310(1):8-17.

Articles citing this article

STIM1-Orai1 interactions and Orai1 conformational changes revealed by live-cell FRET microscopy. J. Physiol. November 15, 2008 586:5383-5401

Activation of Glycogen Synthase Kinase 3beta Promotes the Intermolecular Association of Tau: THE USE OF FLUORESCENCE RESONANCE ENERGY TRANSFER MICROSCOPY. J. Biol. Chem. August 10, 2007 282:23410-23417

Multiple actions of the chemokine stromal cell-derived factor-1{alpha} on neuronal activity. J Mol Endocrinol March 1, 2007 38:365-376

CD4 and CCR5 Constitutively Interact at the Plasma Membrane of Living Cells: A CONFOCAL FLUORESCENCE RESONANCE ENERGY TRANSFER-BASED APPROACH. J. Biol. Chem. December 8, 2006 281:37921-37929



Leptin as an immunological adjuvant: enhanced migratory and CD8+ T cell stimulatory capacity of human dendritic cells exposed to leptin. FASEB J. 2008 Jun;22(6):2012-22.

Functional anatomy of T cell activation and synapse formation. Annu Rev Immunol. 2010 Apr 23;28:79-105.



New drugs approved in 2007
http://www.baylorhealth.edu/proceedings/21_2/21_2_sears.pdf
Selzentry (maraviroc) is a CCR5 co-receptor antagonist in antiretroviral therapy field (Pfizer)

Composition comprising a cell comprising a STIM1 protein and an agent that modulates intracellular calcium and methods of use [United States Patent 7645588]

ORAI Detection Set
http://www.prosci-inc.com/shop/catalog1/ORAI-Detection-Set-p-118.html



http://www.the-aps.org/meetings/eb10/abs/tps-parekh.htm
STIM Proteins: Calcium-Sensors with Multiple Functions
Sponsored by The Physiological Society: UK


Tuesday, April 27� 10:30 AM-12:30 PM
Anaheim Convention Center, Room 303A

Chaired:Anant B. Parekh, Oxford Univ.


http://www.the-aps.org/meetings/eb10/abs/sebm-mulroney.htm
Evolving from Reductionism to Holism: The Future is Systems Medicine
Sponsored by the Society for Experimental Biology and Medicine
Systems Biology (-omics) and Translational Physiology Tracks


Sunday, April 25 ?3:15 PM-5:30 PM
Anaheim Convention Center, Ballroom B

Chaired: Susan E. Mulroney, Georgetown Univ. Med. Ctr.
Howard Federoff, Georgetown Univ. Med. Ctr.


http://www.the-aps.org/meetings/eb10/abs/tpg-basavappa.htm
Integrins: New Insights and Therapeutic Targets
Sponsored by the APS Translational Physiology Group and Liaison with Industry Committee
Systems Biology (-omics) Track


Wednesday, April 28 ?8:00 AM-10:00 AM
Anaheim Convention Center, Ballroom C

Chaired:
Shaila Basavappa, Takeda Pharmaceutical International
Gordon MacGregor, Salix Pharmaceuticals, Inc.




Integrase inhibitor, CCR5 antagonist, fusion inhibitor. Nippon Rinsho. 2010 Mar;68(3):520-4. (AIDS Clinical Center, International Medical Center of Japan. Article in Japanese)

A CCR2/CCR5 antagonist attenuates an increase in angiotensin II-induced CD11b+ monocytes from atherogenic ApoE-/- mice. Cardiovasc Drugs Ther. 2009 Apr;23(2):113-20. (Pfizer)

&

Vascular CXCR4 expression - a novel antiangiogenic target in gastric cancer? PLoS One. 2010 Apr 8;5(4):e10087.

Upregulation of CXCR4 favoring neural-like cells migration via AKT activation. Neurosci Res. 2010 Apr 20.



http://www.the-aps.org/meetings/aps/inflammation/
2010 APS Conference: Inflammation, Immunity and Cardiovascular Disease

Dates: August 25-28
Westin Westminster, Colorado 


The meaning of "collaboration" should be sharing and undertaking

&

Every relationship start from "sharing"


NIH, FDA and personalised medicine
http://chembl.blogspot.com/2010/02/nih-fda-and-personalised-medicine.html

NIH encourages translational collaboration with industry. Nat Rev Drug Discov. 2010 Mar 12.

Weighing risks and benefits of liraglutide -- the FDA's review of a new antidiabetic therapy. N Engl J Med. 2010 Mar 4;362(9):774-7.

Depression-like phenotype following chronic CB(1) receptor antagonism. Neurobiol Dis. 2010 Apr 8. (Pfizer)

Alzheimer's disease: strategies for disease modification. Nat Rev Drug Discov. 2010 May;9(5):387-98. (Eli Lilly)




[ EB#10 ]

http://www.the-aps.org/meetings/eb10/abs/sebm-mulroney.htm
Evolving from Reductionism to Holism: The Future is Systems Medicine
Sponsored by the Society for Experimental Biology and Medicine
Systems Biology (-omics) and Translational Physiology Tracks


Sunday, April 25 � 3:15 PM-5:30 PM
Anaheim Convention Center, Ballroom B

Chaired:
Susan E. Mulroney, Georgetown Univ. Med. Ctr.
Howard Federoff, Georgetown Univ. Med. Ctr.


Paul's final report to FASEB SRC ─ Part II


The poster session on Wednesday evening was a great success, as participants discussed the posters, unpublished research, the current funding climate, and potential collaborations, well into the evening. The facility manager finally had to encourage the participants to exit the conference venue so that they could close for the evening. Every night, discussions continued at the local pub in the village or back at the Chalet. While attendance was relatively low, the participants showed great excitement about the quality of the program and unpublished research that was presented. The quality interactions and discussion continued during the free time between sessions on hikes, raft rides, and biking.

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Eli Lilly :: Strategy is Everything!!

[ Mavericks at Work: Why the Most Original Minds in Business Win ]

Amazon.com: Can you give us a brief summary of your book--in 250 words or less?

Taylor and LaBarre: This book is a report from the front lines of the future of business. It is not a book of best practices. It is a book of next practices--a set of insights and a collection of case studies that amount to a business plan for the 21st century, a new way to lead, compete, and succeed.

Our basic argument is as straightforward to explain as it is urgent to apply: When it comes to thriving in a hyper-competitive marketplace, "playing it safe" is no longer playing it smart. In an economy defined by overcapacity, oversupply, and utter sensory overload--an economy in which everyone already has more than enough of whatever it is you’re selling--the only way to stand out from the crowd is to stand for a truly distinctive set of ideas about where your company and industry can and should be going. You can't do big things as a competitor if you're content with doing things a little better than the competition.

This book is devoted to the proposition that the best way to out-perform the competition is to out-think the competition. Maverick companies aren't always the largest in their field; maverick entrepreneurs don’t always make the cover of the business magazines. But mavericks do the work that matters most--the work of originality, creativity, and experimentation. They demonstrate that you can build companies around high ideals and fierce competitive ambitions, that the most powerful way to create economic value is to embrace a set of values that go beyond just amassing power, and that business, at its best, is too exciting, too important, and too much fun to be left to the dead hand of business as usual.

Who are these mavericks? The core ideas in this book are rooted in the strategies, practices, and leadership styles of 32 organizations with vastly different histories, cultures, and business models. But all of them are business originals, based on the distinctiveness of their ideas and the power of their practices. They are rethinking competition, reinventing innovation, reconnecting with customers, and redesigning work. Together, they are creating a maverick agenda for business--an agenda from which every business can learn.



[
InnoCentive ]

InnoCentive enables solvers to receive professional recognition and financial awards for solving R&D challenges.

"We believe in the power of open innovation, bringing together creative minds to create breakthrough solutions that touch every human life."



FASEB SUMMER RESEARCH CONFERENCES
THE PHYSIOLOGICAL BASIS FOR OBESITY THERAPEUTICS

THERAPEUTICS- MECHANISM OF ACTION / REFINING STRATEGIES
Mechanisms of Action – Pharmacotherapy


*Philip Larsen, Eli Lilly#27
“The future for anti-obesity drug development”


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Stranger in a strange land





Glyceroneogenesis in adipocytes: another textbook case. Trends Biochem. Sci. 28(8), 2003, p. 402-403.


繼續閲讀

Before went to EB#10..

Highlights of the Research Being Presented at EB2010
http://experimentalbiology.org/content/upload/file/Mark%20Your%20Calendar%20IIIApril9.doc

Evolving from Reductionism to Holism: The Future is Systems Medicine (APS)
One of the many symposia presented by the American Physiological Society will be one focusing on the emerging field of personalized, “systems” medicine. With the sequencing of the human genome and availability of high power computational methods and various high through-put technologies, biomedical sciences and medicine will be undergoing revolutionary change. The new technologies and approaches have already spawned the field of systems biology; the new field of systems medicine is the integration and application of biologic and informational sciences, allowing a complex approach to biomedical problems. In medicine, complex computational tools will become essential for deriving personalized assessments of disease risk and management including individualized diagnosis, prognosis, and treatment options. This change, involving the use and analysis of enormous quantities and variety of data, will require new types of physicians and researchers - ones with a grasp of modern computational sciences, “-omic” technologies (genomics, proteomics, metabolomics, etc.), and a systems approach to medicine. (Sun., 4/25)


AAA Annual Meeting at EB 2010
April 24 - 28 • Anaheim, CA

http://anatomy.org/Meetings/meeting_highlights_10.htm

KEYNOTE SPEAKER
Dr. Leroy Hood ─ President (Institute for Systems Biology)

Systems Approaches to Biology & Disease: Integrating Discovery & Hypothesis-driven Paradigms
Monday, April 26, 5:00-6:00 PM, Room 213CD

The challenge for biology and medicine in the 21st century is the need to deal with its incredible complexity. One powerful way to think of biology is to view it as an informational science requiring systems approaches. This view leads to the conclusion that biological information is captured, mined, integrated by biological networks and finally passed off to molecular machines for execution. Systems approaches are holistic rather than atomisticnd employ both hypothesis-driven as well as discovery-driven approaches. Hence the challenge in understanding biological complexity is that of using systems approaches to deciphering the operation of dynamic biological networks across three time scales of lifeevelopment, physiological and disease responses. I will focus on our efforts at a systems approach to diseaseooking at prion disease in mice. We have just published a study that has taken more than 5 yearshat lays out the principles of a systems approach to disease including dealing with the striking signal to noise problems of high throughput biological measurements and biology itself (e.g. polymorphisms). I will also discuss the emerging technologies (measurement and visualization) that will transform medicine over the next 10 yearsncluding next generation DNA sequencing, microfluidic protein chips and single-cell analyses. It appears that systems medicine, together with pioneering changes such as next-generation DNA sequencing and blood protein measurements (nanotechnology) and as well as the development of powerful new computational and mathematical tools will transform medicine over the next 5-20 years from its currently reactive state to a mode that is predictive, personalized, preventive and participatory (P4).

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Paul's final report to FASEB SRC ─ Part I


The business meeting was held after session 5. There was unanimous agreement to hold the next conference in three years in the summer of 2012, and the majority of participants wanted to pursue the Steamboat location for that event. The organizers for the next meeting will be:

Anthony Comuzzie, PhD, Southwestern Biomedical Research Center
John Thyfault, PhD, University of Missouri Columbia
Kellie Tamashiro, PhD, Johns Hopkins University
Brian Baldo, PhD, University of Wisconsin-Madison
Steve Smith, MD, Pennington Biomedical Research Center

As you can see there were many who were interested in getting involved with bringing the next meeting to fruition in 2012. This is a collection researchers with a broad range of expertise in obesity-related research, with a geneticist, an integrative physiologist, a maternal-fetal physiologist, a neuroscientist, and a clinician. These individuals are well-known and well-published in their respective areas, but normally do not pass through the same circles at national and international meetings. Their plan is to develop a program with a broader scope and interest to draw on a broader base of attendees. In our initial discussion, they discussed an interest in taking a “Systems Biology” approach to the theme of the next meeting.


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Hello, World!!

FASEB SUMMER RESEARCH CONFERENCES ─
THE PHYSIOLOGICAL BASIS FOR OBESITY THERAPEUTICS

https://secure.faseb.org/faseb/meetings/Summrconf/Programs/11710.pdf



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