Monday, March 30, 2009

Journal Club

Dear Dato'/Prof/ Assoc. Prof/ Dr/ colleagues,

I am pleased to invite all of you to our weekly IMMB journal club session that will be held as follow:

Title : ‘Comparison of Weight-Loss Diet with Different Compositions of fat, Protein, and Carbohydrates'
Presenter : Miss Suhana Hamzan
Chairperson : Miss Nurul hajar Ghazali
Venue : IMMB Meeting Room, Level 13, Block 5, S&T Building
Date : 1st April 2009, Wednesday
Time : 12.45 noon

All are welcome.

Refreshment will be provided

Thank you.

Monday, March 23, 2009

Jurnal Club

Dear Dato'/Prof/ Assoc. Prof/ Dr/ colleagues,

Please be informed that there will be an IMMB Journal Club. Below are the details:


Title : "AOE activities and expression levels in the kidney during development of

hypertension in SHR".

Presenter : Prof Dr Harbindarjeet Singh

Chairperson : Mr Mohd Shahir Abdul Rahman

Venue : IMMB Meeting Room, Level 13, Block 5, S&T Building

Date : 25th March 2009, Wednesday

Time : 12.45 noon


All are welcome.


Thank you.



Wednesday, March 18, 2009

RESEARCH NEWS OF INTEREST

New Target for Heart Failure Therapy Identified
Drug Discovery & Development -
March 18, 2009

A novel signaling pathway plays a significant role in the production of aldosterone, a hormone that promotes heart failure after a myocardial infarction, according to a study conducted by Thomas Jefferson University researchers.
The findings show that aldosterone production is mediated by a protein called b-arrestin-1. b-arrestin-1 binds to angiotensin II receptors when they are activated by angiotensin II.
Aldosterone is secreted by the adrenal cortex. Its levels are elevated in chronic heart failure, and its presence contributes to morbidity and mortality of the disease. It contributes to heart failure progression and diminished cardiac function after myocardial infarction.
The production of aldosterone was previously thought to be solely the result of the activation of G-proteins, which are also activated when angiotensin II binds to its receptors, according to Anastasios Lymperopoulos, Ph.D., a Post-Doctoral Research Fellow in the Center for Translational Medicine and the George Zallie and Family Laboratory for Cardiovascular Gene Therapy at Jefferson Medical College of Thomas Jefferson University.
For more please use the link below

http://www.dddmag.com/news-target-for-heart-failure-therapy-031809.aspx
Health Protection Agency Culture Collection

Cross-Contaminated & Misidentified Cell Lines

The ECACC has published on its webpage various informations concerning cross-contaminated or mis-identified cell lines, how these cell lines can be tested for authencity etc. For the original postings and further information, please follow the following link.

http://www.hpacultures.org.uk/services/celllineidentityverification/misidentifiedcelllines.jsp


For informations on cross-contamination between cell lines found in the literature please read the two articles below. According to the ECACC survey of the scientific literature up to 20% of published work based on the use of human cell lines specifiec lines are suggested or known to be mis-identified1,2. This is not a small number. Therefore everybody who is working with cell lines should look into this matter.


1. MacLeod et al., (1999) Widespread intraspecies cross-contamination of human tumor cell lines arising at source. Int J Cancer 83(4) 555-563 (Cell line: ECV304)
2. Drexler HG et al. (2003) False leukemia-lymphoma cell lines: an update on over 500 cell lines. Leukemia, 17(2):416-426.

Tuesday, March 17, 2009

Genome Web Daily News

MicroRNA Profile Predicts Acute Kidney Transplant Rejection

March 17, 2009
By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a paper appearing online last night in the Proceedings of the National Academy of Sciences, a team of American and French scientists identified a microRNA expression profile that can predict which kidney transplant patients will suffer acute transplant rejection and reduced transplant function.
Using arrays, the researchers identified more than a dozen miRNAs that were differentially expressed in cases of acute kidney transplant rejection compared to stable transplants. They subsequently validated six of these in a larger, independent cohort, linking miRNA levels to both acute rejection and transplant function.
Interestingly, rejection samples and peripheral blood mononuclear cells shared some highly expressed miRNAs, while miRNAs that were under-represented in rejection samples were found at high levels in primary human kidney epithelial cells. Together, the results support the idea that kidney transplant rejection occurs as recipient immune cells enter and attack transplanted tissue. Along with such insights, the team suggested that miRNAs may also serve as markers for kidney transplant or renal allograft status.
"Our studies, in addition to suggesting a cellular basis for the altered intragraft expression of miRNAs, propose that miRNA expression patterns may serve as biomarkers of human renal allograft status," senior author Manikkam Suthanthiran, a nephrology and transplantation researcher at the New York-Presbyterian-Weill Cornell Medical Center, and his colleagues wrote.
Although organ transplantation has become fairly routine, transplant recipients must continue taking immuno-suppressive drugs throughout their lives to prevent transplant rejection. Such rejection occurs when the recipient's immune system recognizes the transplant as foreign and mounts an immune response against it.
Because previous research suggests gene expression — including the expression of genes involved in immunity, cell cycle control, and metabolism — shifts dramatically during transplant rejection, Suthanthiran and his team decided to look at whether they could find miRNA expression changes that heralded acute transplant rejection.
They evaluated 33 transplanted tissue or allograft biopsies, taken from 32 adults who had had kidney transplants — a dozen from 11 individuals with acute rejection and graft dysfunction and 21 from individuals with stable transplanted kidney function.
From these, the team initially evaluated miRNA profiles in three of the acute rejection biopsy samples and four stable transplant samples using an Applied Biosystems TaqMan low-density array human microRNA panel representing 365 mature human miRNAs.
They found roughly 174 miRNAs expressed in each of the samples. But the same miRNAs were not present in all of the biopsies. The researchers identified 17 miRNAs that were expressed at different levels in the acute rejection samples than they were in the stable transplant samples. Of these, ten were under-expressed and seven were over-expressed in the acute rejection samples.
Using modified TaqMan miRNA assays, the researchers confirmed the differential expression of six of the miRNAs in an independent validation set of nine acute rejection and 17 stable transplant biopsy samples. The acute rejection samples showed increased expression of miR-142-5p, miR-155, and miR-223 and decreased expression of miR-10b, miR-30-3p, and let-7c.
All six miRNAs were also linked to the transplanted kidney's function, specifically glomerular filtration rate, though miR-142-5p and miR-10b were most strongly associated with this function.
Of the differentially expressed miRNAs, miR-142-5p and miR-155 seem to be the most promising biomarkers for predicting kidney transplant status. Both predicted acute rejection with 100 percent sensitivity and 90 percent to 95 percent specificity. The other four miRNAs, while diagnostic, predicted rejection less accurately.
When they used real-time quantitative PCR to assess messenger RNA levels in the transplant tissue, the team found that the levels of miR-142-5p, miR-155, and miR-223 correlated with the levels of mRNA for immune genes such as CD30 and CD20. Overall though, miRNA levels appeared to more accurately predict transplant rejection than CD3, CD20 or other mRNA levels tested.
Consistent with the notion that acute transplant rejection involves immune system infiltration of transplanted kidney tissue the team found that rejection miRNA profiles were more similar to normal human peripheral blood mononuclear cells than to primary human kidney epithelial cells.
And miRNAs previously linked to immune system function were among those that were highly expressed in rejection samples whereas miRNAs that appear to contribute to kidney tubule function were down-regulated.
The researchers say even more research is needed to understand just how miRNA profiles are altered in the graft-infiltrating and transplant epithelial cells. But, they added, their results suggest miRNA expression patterns may be a promising tool for predicting and monitoring patients' kidney transplant status.

Invitation to Journal Club Presentation 18 March 2009



Dear all,

Last week we had a presenter from outside of UiTM talking about how we can benefit from NUNC products related to cell culture and etc. To me it was a great presentation and we should think of inviting them again in the near future. Now lets come back to this week presentation. Thank you Prof Justin for his acceptance to be with us. Hope we can share your knowledges from the presentation and you are most welcome again to update us with the latest findings from your research. For all, the graphical form or small poster of invitation is now available. Please distribute to your colleagues. Thank you.

Saturday, March 14, 2009

Asthma

β2-Adrenoceptor signaling is required for the development of an asthma phenotype in a murine model

Nguyen, L. P. et al. Proc. Natl Acad. Sci. USA 106, 2435–2440 (2009) Article PubMed

β2-Adrenergic receptor (β2AR) agonists are used in the management of asthma, but their chronic use is assoicated with loss of disease control. This paper demonstrated the paradoxical result that β2AR signalling — by constitutively active receptors — is required for the asthma phenotype in animal models. A β2AR inverse agonist attenuated asthmatic symptoms, highlighting the potential of inverse agonists in this condition.
The Scientist

By Steven Wiley
-------------------------------------------------------------------------------------------------
The Problem of Perception

http://www.the-scientist.com/article/display/55467/


Your interpretation of results depends on more than just the results.

Another group felt that our computer model was a poor substitute for their own scientific intuition regarding what was happening.

There is a common perception among young students that the surest path to resolving scientific controversies is to design a clever experiment, one that will definitively resolve conflicting hypotheses. However, I have found that most scientific controversies do not revolve around specific experimental data, but instead are disputes over data interpretation.

Data interpretations depend on a scientist's underlying assumptions and worldview. For example, a molecular biologist might think of protein expression as an outcome of mRNA levels, whereas a biochemist might think in terms of synthetic and degradation rates. Both are right, of course, but each might expect different reasons for a change in the amount of a protein. Our perspective and assumptions regarding how living systems work defines us as biologists, which is why arguments over interpretations can get so nasty. If another scientist disputes the validity of your viewpoint, it can impact your reputation as well as your ego.

I experienced a dispute over data interpretation in the late 1980's that turned somewhat contentious. My laboratory was investigating the role of tyrosine kinase activity in the endocytosis of the EGF receptor in collaboration with Gordon Gill at the University of California, San Diego. By using a series of kinetic measurements, we concluded that kinase activity was necessary for ligand-induced endocytosis and down-regulation, whereas a competing group thought that it was not. What was interesting about the dispute was that the primary data gathered by both groups were essentially identical. The main difference was in how the data were interpreted.

We were calculating receptor endocytosis rates on a per receptor basis whereas the other group used a per cell basis. In the case of receptors with kinase activity, EGF binding accelerated endocytosis 10-fold, which caused cell-surface receptors to drop 10-fold. Thus, the net rate of endocytosis per-cell (rate x receptors) did not change in response to kinase activity, making it appear to have no effect on receptor internalization.

It was hard to convince the other group that differences in a simple rate calculation would make a big difference in what they concluded from the data. However, we were working from a computational model of endocytosis that allowed us to try out different sets of assumptions and see how they would affect the system's behavior. The other group felt that our computer model was a poor substitute for their own scientific intuition regarding what was happening. As they stated at the time, "(Our) results are in agreement with the results of Chen et al. (Cell, 59:33–43,1989), but in conflict with their interpretation. By applying a simple mathematical model (J Cell Biol, 107:801–10, 1988), the lack of down-regulation of kinase-negative mutants was misinterpreted as an indication for reduced endocytosis." 1

Over time, our view prevailed and it is now generally accepted that the kinase activity of the EGF receptor is required for ligand-induced endocytosis. 2 Interestingly, our view was vindicated not because people came to accept our use of computational modeling, but because our hypothesis was more successful in predicting subsequent experimental results. Scientists don't generally care about who is right or who is wrong in a dispute. They want a conclusion that can help predict their own experimental outcomes. Science is built brick by brick from ideas and concepts that can lead to the next successful series of experiments and concepts. If an idea doesn't support the next brick, it is discarded. It's natural selection in science.
Scientific disputes seem inevitable in any career, but mine gave me a keen appreciation of the need for caution in accepting simple interpretations of the behavior of complex systems. In science, we do not gather facts. We make observations. Our interpretation of observations is only as good as our assumptions and conceptual frameworks.

The ability of a simple computer model to correctly interpret a seemingly non-intuitive result was also quite revealing. It convinced me that as biology becomes even more complex, we will need computational models even more to help us out. They can not only let us see past our inherent interpretational biases, but can also be used to design experiments to test our concepts—a foundation for building a truly predictive biology.

Steven Wiley is a Pacific Northwest National Laboratory Fellow and director of PNNL's Biomolecular Systems Initiative.

References

1. A. Ullrich, and J. Schlessinger, "Signal transduction by receptors with tyrosine kinase activity," Cell, 61:203–12, 1990.
2. A. Sorkin, and L.K. Goh, "Endocytosis and intracellular trafficking of ErbBs," Experimental Cell Res, 314:3093–106, 2008.
FREE ARTICLE

A new mechanism for Alzheimer's?

Genentech scientists have proposed a new mechanism for Alzheimer's disease pathogenesis in a recent Nature paper and have identified a trio of new AD targets. Will this work lead to a major change of focus in developing drugs for the disease?

http://www.nature.com/scibx/journal/v2/n8/full/scibx.2009.300.html

Thursday, March 5, 2009

Welcome to Weekly Journal Club Presentation


Dear all,

This week we will have a presenter from outside of UiTM. The topic will be about NUNC product and for those who involve or plan to start doing research related to cell culture, please join us. As part of our commitment starting from this week we will send you the announcement of this event in a graphical form or small poster, so that you can redistribute to your colleagues and let them know thus allow them to join us too. Thank you.

Tuesday, March 3, 2009

Journal Club


Dear Dato'/Prof/ Assoc. Prof/ Dr/ colleagues,

I am pleased to invite all of you to IMMB journal club session that will be held as follow:

Topic : NUCLEOTIDE SEQUENCE PLAMID OF HAEMOPHILIA
INFLUENZAE

Presenter : DR. ZAINI MOHD ZAIN

Chairperson : MR. MOHAMAD ROS B. SIDEK

Venue : IMMB Meeting Room, Level 13, Block 5, S&T Building

Date : 4th MARCH 2009, WEDNESDAY

Time : 12.45 noon


Refreshment will be served. All are welcome.
Thank you.



ZD