Parkinsonism can be classified into:

1. Primary/idiopathic “of unknown cause” which is mostly due to degeneration of dopaminergic neurons (a.k.a Parkinson’s disease)
2. Secondary to viral infection as encephalitis & meningitis; drug-induced, e.g., antipsychotics; or due to brain damage caused by trauma, anesthetics,  or toxins as MPTP (a contaminant of street-drugs).

Arvid Carlsson

You may know that the Nobel Prize associated with Parkinson’s disease didn’t go to Dr. James Parkinson who described it in an essay he wrote back in 1817 calling it “The Shaking Palsy”.  It went jointly to Arvid Carlsson, Paul Greengard, and Eric R. Kandel in 2000 (To find out more about the story, here’s the Nobel lecture by Dr. Carlsson). Carlsson and colleagues discovered dopamine as a potential NT in 1957. After that, in 1960, Hornykiewicz and his postdoctoral fellow, then, Ehringer observed the decrease of dopamine levels in Parkinson’s disease patients, and levodopa successful trials started after that, in 1961.

J. Robin Warren

What does Dr. Warren, the scientist whose discoveries led to a paradigm shift in physiology, who said out loud that peptic ulcer is an infectious disease caused by Helicobacter pylori, the gut bacteria? What does he have to do with parkinsonism? Note that: J. Robin Warren and Barry J. Marshall also won Nobel prize in medicine for 2005 for their discovery.

Helicobacter-induced parkinsonism!!

What I am trying to say here—and didn’t say in my essay—is that there is a hypothesis, Helicobacter-hypothesis, that strongly provides another cause of idiopathic parkinsonism, which will not be idiopathic any more, and this cause is H. pylori (Altschuler, 1996). Or to be more accurate, I will say parkinsonism associated with H. pylori. Dobbs and colleagues have carried out well-controlled studies and observed a significant conversion in patients with Parkinson’s disease from malignant into benign parkinsonism after successful eradication of their H. pylori, even with no levodopa administration. The rationale behind this theory is that: H. pylori induces an autoimmune reaction against mitochondria, then a systemic inflammatory response with the whole gang of inflammatory mediators and antibodies reaching and crossing the deficient areas or areas with increased permeability of the blood-brain barrier, causing parkinsonism. And the blood profile can prove the Helicobacter-hypothesis.

   Send article as PDF to

Come on! FOR REAL?

Sadly very true and it is not even that infrequent either! I only became aware of this after reading about a study, where researchers in HMS, led by Dr. George M. Church, collected soil samples in an experiment, attempting to search for more bio-diversity and were stunned to see that as they added antibiotics to these bacterial cultures, the bacteria didn’t seem to mind at all!

Unlike human beings, bacteria tend to like sharing. The more they share their strategic defenses, the more prosperity they end up living in. Again, to our dismay, such fear was translated into reality, as this has already extended to the pathogenic minorities of the bacterial world in a new study, published in January in the International Journal of Tuberculosis and Lung Disease. Scientists, in China, have stumbled upon a strain of tuberculosis-causing bacteria, called Mycobacterium tuberculosis, INCAPABLE of growing adequately in the absence of rifampicin. This is as ominous as such news can get.

This strain was discovered as physicians attempted to treat a TB-infected patient with a regimen which included rifampicin. Unexpectedly, his condition worsened and only upon the removal of rifampicin did he start feeling better, until eventually full recovery. Already, reports of multidrug-resistant TB “MDR” have been around for some time. Normally, the treatment course includes more than 1 drug to be able to effectively kill the bacteria. Apparently, the bacteria have found a way to get around that!

We can only wonder: which antibiotic is next?

   Send article as PDF to

The Ozcan Research Group at UCLA will already begin their field tests in Africa concerning the new cell phone/microscope gadget. I had to see to believe. Aside from all the engineering & technological aspects, which I am sure are quite many, if this were to be actually implicated worldwide, the possibilities of its application are endless, including, but not necessarily limited to, pretty much all of the blood-borne diseases. For instance, malaria, which is fairly common in many African countries, can be instantly diagnosed. The hospital would get the patient’s blood picture, through the cellular networks for analysis by physicians and there you have it.

   Send article as PDF to

Dr. Richard J. Roberts

I will start with this talk by Dr. Richard Roberts, who received the Nobel Prize in Physiology or Medicine in 1993 for the discovery of split genes and mRNA splicing in 1977. He is now joint Research Director at New England Biolabs. Dr. Roberts entitled his talk: “Collaborating to bridge the gap between computation and experimentation”. I will try to sum it up for you.

I. Let’s start with stating this fact that Genomics is rapidly taking over the field of biology, at the research level at least.

Examples:

1. Sequencing of the human genome or “The Human Genome Project” provides the basis of the emerging field “personalized medicine”.
2. Plant genomics are unbelievably important for food and –maybe- for energy production purposes, unicellular plants mostly.
3. Ocean organisms are very interesting, as they produce potential new antibiotics and many other useful substances.
4. Bacteria and archaea are making up to 50% of the living biomass.

Bacteria are everywhere, they live in the oceans, the soil -plants require them for nitrogen fixation- animals and us; our gut, skin, nose and mouth. Most of these bacteria we know absolutely nothing about because we can’t grow them on cultures.

But this is about to change now thanks to DNA sequencing.

II. So, the core of today’s science is DNA sequencing… but unfortunately, DNA sequencing has its drawbacks.

1) DNA sequencing is getting faster and cheaper in a rate that is exceeding our ability to understand the function or the biochemical pathways of every single gene sequenced. Or, if we’re really lucky, we can make a guess -based on sequence similarity- that this gene, for example, encodes for a “hydrolase”, but just a hydrolase with no clue about the exact biochemical pathways it’s involved in or its substrate.

Dr. Roberts gave this interesting simile that getting more and more DNA sequences of bacteria is like getting a car with a list of all its parts with no idea about how they fit together or how they work. Biology is about understanding how life works. If we’re talking about synthesizing life today, we have to understand how life works first. He dreams that before he dies, he can understand how a very simple bacterium actually works, what is the chemistry that is going on there?

So, the first problem is in the very rapid growth in DNA sequencing without a similar growth in annotation/renaming/finding the function. Here’s a quite older graph showing the growth of sequence databases and annotations from 1982 till 2006, close to the one Dr. Roberts presented, from 1995 till 2009. If you can get to a newer one, please do not hesitate to comment on the post and add its link.

The growth of sequence databases and annotations (1082-2006) - Argonne National Laboratory

2) The computer is not enough! Do the biochemistry in the lab! In spite of the large amount of money spent on sequencing different organisms; we still are not making any progress in understanding them. This might be that when we get the DNA sequence, translate it into its corresponding amino acid sequence, our best shot then is to compare it to the existing protein sequences in the databases to know how it looks like what and thus predict its function. If two protein sequences look the same, there’s a chance, not a guarantee, that they have the same function, because if there’s a one amino acid difference, they may have different substrates and thus different functions. How to tell? The computer is not enough! Do the biochemistry in the lab! This will lead us to the third problem.

3) All substrates are not available to all labs all the time. So, one lab can’t determine the function of all genes on earth. He gave this example: if you want to assay a specific disaccharide hydrolase; to determine its substrate, you need to have disaccharide combinations of all possible sugars and test it on them.

4) Lack of good funding for biochemistry. Funding agencies think that biochem- is an “old-fashioned” field! They are funding the more appealing genome-wide studies, which is very superficial.

III. Dr. Roberts’ suggestions for a solution: “COMBREX”
Identifying Protein Function—A Call for Community Action.

Dr. Roberts and colleagues have got an NIH fund in October 2009 to establish COMBREX (maybe: COMputational Biology Reading EXperiments). The work flow will be very much like this:

Step1: Establishment of a database. From 1200 complete bacterial and archaeal genome sequences, computational biologists groups generate protein families/domains of unknown function (DUFs), predict the function based on sequence similarity and establish a database.

Step2: Coordination of the efforts between biochemistry labs, experimentalists/biochemists (young grads, even technicians) offer a proposal to test those predictions, gain an exclusive access to those genes of interest for 6 months + a small grant (5,000-10,000 USD) to carry out single gene studies. If we know one protein’s function, we know the function of the whole protein family.

Step3: Making of a Wikipedia-type page for suggestions and predictions.

Step4: Establishment of a journal to publish the findings.

IV. What genes should we focus on/start with?

Dr. Roberts suggested this list, which is ordered in a descending order:

1) Genes abundant in many many different organisms; in humans, animals, bacteria… etc. Those are likely to have conserved important functions.

2) E. coli, the most widely used and so-called “the best studied” organism, we can make a full characterization of it.

3) Helicobacter pylori, to understand the biochemistry of such an important pathogen that we know nothing about.

4) Identify cloned, translated and frozen open reading frames (ORFs) products.

V. Who can help?

Dr. Roberts said almost everybody, computational biologists to predict, biochemists to test, geneticists, as personnel university students -even high school students it can help them to get a genuine science project-, retired professors to supervise and maybe get back to the lab, and funding agencies.

You can watch this talk and most of the conference’s talks via the Bibliotheca Alexandrina webcast.

Dr. Roberts' talk at BioVision Alexandria 2010

Richard Roberts with BioVision Alexandria 2010 attendees

   Send article as PDF to

Ever since heart transplant surgeries were a success in 1967, scientists were skeptical about what is now referred to as, Cellular Memory Phenomenon.  This was provoked through the close observation of recipients, who repeatedly report bizarre distant memories and new personal preferences. Exactly how much can the cells of an organ, other than the brain, mainly the heart in this case, store memories? The Discovery Channel aired a documentary titled “Transplanting memories” where various experts gave their opinion on the matter.

If such phenomenon truly exists, where are these memories located inside the cells? Could it be the DNA? But this is sheltered inside the nucleus and remains entangled except when cellular division takes place. This makes its access difficult, but after all, it cannot be THAT difficult, otherwise mutagenic agents wouldn’t have succeeded.

Possibly proteins. Dr. Candace Pert stated that, since the brain and human organs are linked through a massive network of peptides. She said “I believe that memory can be accessed anywhere in the peptide/receptor network. For instance, a memory associated with food may be linked to the pancreas or liver, and such associations can be transplanted from one person to another.”

Source:  The Medical News

Image Source: Hiveworld

   Send article as PDF to

The webinar meant to have speakers who are experts in their areas and to cover different segments dealing with searching, analyzing, and reusing scientific articles. The webinar was moderated by Ryan Jones, President of Pubget, and the speakers represented:

• Publishers: Peter Binfield, Managing Editor, PLoS One
• Libraries: Marcus Banks, Manager of Education and Research Services, UCSF
• End Users: Ansuman Chattopadhyay, PhD, Bioinformatics, University of Pittsburgh
• Tools: Ramy Arnaout, MD PhD, Chairman and CEO, Pubget

Peter Binfield talked about his experience with PLoS One as a journal established in the digital era, and all of its content is digital. He was much concerned with how to monitor the “reuse” of an article and the tools incorporated in PLoS to achieve that. PLoS uses multi-dimensional, article-level metrics rather than a monolithic system like impact factor. PLoS metrics system enables every one to know the exact usage of an article, downloads and views. PLoS also enables commenting, rating, discussing, selecting a part/line and writing a note about it, sharing/bookmarking, and showing trackbacks to blogs and citations.

Marcus Banks said that the digital “libraries” are still in need of a librarian to analyze, organize and link publications. He also talked about the need of a tool that enables researchers to highlight only the parts of a publication that they need, instead of consuming time reading through the whole publication. He talked about sharing tools like: Zotero, Mendeley, Del.icio.us, RefShare, CiteULike, and Pubget.

Representing the end-users was Ansuman Chattopadhyay on the stand. His presentation was entitled: “Beyond PubMed: Next generation literature searching”. With PubMed, it’s difficult to narrow down your search and reduce the number of the results/hits, but this could be achieved by the newer Google-like tools such as:

• GoPubMed, which gives the users suggestions as they are typing
• Novoseek, which categorizes search results into: diseases, pharmacological substances, genes/proteins, procedures, organisms, etc.

and text-similarity tools like:

• eTBLAST, a web server to identify expert reviewers, appropriate journals and similar publications (the paper)
• JANE, Journal/Author Name Estimator
• DeepDyve

One point I didn’t get is the need of a “daily journal of negative results”.

Ramy Arnaout presented Pubget as a search tool that is:

• like an on-the-web Acrobat Reader (the search results are the PDFs of the papers)
• able to deliver science at speed
• legal and free, as researchers use their institution’s license to get to all publications including the non-open-access ones
• user-friendly, as a user chooses from a list of publications a paper that opens in the same window

The concerns that all four speakers expressed at the end of the webinar were mostly:

• How to achieve the balance between delivering science and preserving copyrights, a problem that is being partly solved by Open-Access journals.
• How to tell the end-user what is related to his/her field.
• Although everything is “online”, the challenge is how to get to it and use it.
• How to interact with the end-users and make them discover the tools/features of search engines, this can be solved by workshops and tutorials.

I do thank Pubget for giving me the chance to attend this very informative webinar by making it  freely available.

Edited on Dec 22, 2009 09:31 p.m. CLT

   Send article as PDF to

When I first read this commentary “The Case for Biocentric Microbiology”* by Dr. Ramy Aziz, published by the journal “Gut Pathogens, I was shocked! The article was presenting a very different perspective, at least different from what I always dreamed of as a pharmacy student, to kill the bad bugs by designing an effective, highly selective chemotherapeutic! Plus it was my first time to read an opinion article, and I used to take the microbiology courses for granted; “this is a bad microorganism, causing this bad infectious disease with serious manifestations including these, diagnosed by the following and the antibiotic of choice is this.” And then Dr. Aziz came with this article with the cool, simple and exciting writing style that keeps one alerted the entire article, gathering all those thoughts and examples of our human-centered/self-centered view of microbiology.

Four parts I enjoyed the most in the commentary:

• The tabular form of “differences between the anthropocentric and biocentric views of microbes.”
• The final balancing paragraph -the conclusion.
• The “competing interests” part, which is funny.
• The questions part, which is an excellent idea to open up discussions, especially for those who are not-natural-born brain stormers like me!

Even though microbiology is a new science, it suffers from anthropocentric view that Galileo suffered from; starting with the field’s name itself, “microbiology” -liked what Dr. Elio Schaechter mentioned: “Small,” says who? Not the microbes… till the funding agencies that give priority to studying bad microbes (i.e., pathogens), and good microbes (i.e., fuel-producing and yogurt-making bacteria) nothing else!

Bacteria convention - http://www.towardslife.com/

We, in our human-centered view; automatically classify any newly-discovered bacterium to fall into one of three categories: the good, the bad and the ugly… no, not that one! They are: the useful guys, the harmful guys and the just-existing guys. Now, let’s take a look at the biocentric view of microbes: Humans and microbes share many ecosystems. To microbes, humans are just an ecosystem that is a “relatively safe” habitat with a source of nutrition.

As victims, we think about pathogenesis/infection as it’s shedding from the immune system, invasion and toxin production; but microbe-oriented microbiologists/bacteria whisperers know that, to bacteria, pathogenesis is  just defense, seeking nutrition, and excretion of metabolic byproducts. Being pathogenic or opportunistic is not their reason of existence, it’s just a form of adaptation to survive in this hostile environment (aka the human body).

You do not believe me!? OK, bacteria lived –happily- thousands of millennia before mammals and humans, so their reason of existence can’t be to harm humans, like what Dr. Aziz is mentioning: “Who attacks whom”, are the bacteria the “one” that start the fight, or is it the human immune system that starts the war against them?  A very interesting example to understand adaptation is Legionella pathogenesis, and how they adapted to human macrophages because they used to survive in amebas, which are similar to our macrophages.

Back to the basic question, is it a luxury or a necessity?

Studying “all” bacteria from their perspective will help us in understanding pathogenesis and subsequently developing strategies to combat infectious diseases (immunization and design highly selective chemotherapeutics), will give us a better idea of the tree of life and the metabolic map, and studying environmental microbiology will allow us to meet new “useful” microbes like what happened with the PCR Taq-polymerase, we knew how to make use of this bacterial polymerase that can work at those very high temperatures required for the PCR steps.

Here are two interviews about the commentary covering two segments of readers, the first one is with Dr. Betsey Dyer, Professor of Biology at Wheaton College, and the second one is made with Radwa Raed, a micro-writer and a final-year FOPCU student:

1- What is your opinion about (the commentary)? To what extent do you find it compatible with your bacteriocentric view of bacteriology? How strong are the arguments?

Dr. Betsey D. Dyer, Professor of Biology at Wheaton College.

“I thoroughly enjoyed Ramy Karam Aziz’s article “The Case for Biocentric Microbiology.” I think he is absolutely right that some old fashion thinking about the divisions of microbiology and anthropocentrism in general have hindered a more complete understanding of the microbial world. I also think Dr Aziz is quite bold and daring. I’m not sure I could have gotten such forceful statements accepted for publication! Good for “Gut Pathogens” to print it! I hope Dr Aziz gets lots of readers and citations.”

2- How did (the commentary) change your point of view? Are you with or against the biocentric view for microbiology? Do you think about it as a view against, or at least far from, your beliefs as a pharmacy student dreaming of fighting diseases? What are your opinions regarding studying environmental microbiology in pharmacy school?

Radwa Raed, Pharmacy student, Faculty of Pharmacy, Cairo University – Egypt.

“From my humble point of view, I would have to agree (with the biocentric view of microbiology). It goes without saying that studying more about certain bacteria “the ones some would consider to be of the least priority” will definitely expand our knowledge about the overall, and in many cases analogous or even similar, methods of survival, adaptation to existing conditions, etc.., which all pretty much ultimately serve medical microbiology. Plus, leaving a whole chunk, simply unexplored, can only raise several “what if” questions; one of which, that comes to mind, is what if the simplicity and less dramatic forms of life could help researchers better grasp the machinery behind these fascinating little creatures

As for studying environmental microbiology in pharmacy schools, I would have to oppose the idea, because the field of pharmaceutical science is taught so the future students can come to understand, and hopefully later suggest, treatment methods against pathogenic microorganisms, prophylaxis, and so forth..so studying the harmless ones would not point in this direction. It can only lead them to drift away from the pharmaceutical science branch of study into a more microbiology-oriented career.”

You can read the paper, share your comments and debate the arguments here, and you can also vote for it on BioWizard.

––

*Full Citation:

Aziz, R. (2009). The case for biocentric microbiology Gut Pathogens, 1 (1) DOI: 10.1186/1757-4749-1-16

   Send article as PDF to

Borrelia burgdorferi

Borrelia burgdorferi is motile through the undulation of its axial filaments. It is transmitted to humans by the bite of infected ticks (Ixodes scapularis and Ixodes pacificus) and cause a serious progressive disease called lyme disease.

The story of lyme disease began in 1975 when a mother, with her children in lyme city in the United States, was admitted to a hospital with signs of rheumatoid arthritis. It was a mysterious case until the discovery of Borrelia burgdorferi and that is how the disease got its name, when it was discovered in 1982. Symptoms and signs of lyme disease can be categorized into three phases:

Phase (1): An early localized skin rash, characterized by inflamed red edges with a clear white center at the site of insect bite, appears and is called “erythema migrans“.

Erythema migrans

Phase (2): The rash resolves as the bacteria begin to move into the blood stream towards their target organs like large joints, heart, and nervous system.

Phase (3): Inflammation of heart muscle leads to abnormal rhythm, meningitis, confusion and finally arthritis.

Treatment in the early phase is an easy mission by amoxicillin or doxycycline, orally for few weeks. However, the recommended regimen in late stages include parenteral ceftriaxone, analgesics to control the severe pain, and anti-inflammatory drugs, usually required for months .

Images credits:
Borrelia burgdorferi: http://www.wadsworth.org/databank/hirez/hechemy2.gif
Erythema migrans: http://phil.cdc.gov/PHIL_Images/9875/9875_lores.jpg

   Send article as PDF to

It can simply be defined as a link between biology and computer science, in which the biological data is processed and computed through software, to yield an output, that is later interpreted in different ways.

Biological data indicates the nucleic acid or protein sequences, their simple or complicated forms, whereas the software is the computer program, specially designed for processing these data in a certain way, done using a certain algorithm (it is a recipe to solve a program problem). The data output is usually numerical or visual (often graphical), but mostly it needs to be well understood. The last one is the key point in the bioinformatics.

What is the need of bioinformatics?

In the research field, we need to be led to certain road, to choose one way or another, or to try many options until we define our research plan. Bioinformatics simply brings the solutions into your hands by a few mouse clicks.

One simple example to make it all clear is the PCR (Polymerase Chain Reaction). We always need to design a primer to trigger our reaction. If we did this through the ordinary ways, we would have to practically try out so many primers and this would surely take a tremendous amount of time. Now, what if you are computer- and internet-literate? You can simply use software to get many primer options for the DNA piece under investigation; doesn’t this save time, efforts and money?

Can bioinformatics be useful in different ways, other than the PCR example?

Some people may think that using bioinformatics is limited to some fields of biological research, and some others might think it is only a matter of prediction, which always needs to be evaluated for its accuracy, specificity and efficiency. But indeed, bioinformatics can be used in the analysis of nucleic acids and proteins.

Analysis?!! That is a vague word, how can you analyze a protein using bioinformatics?

Now you’ll see what bioinformatics can do for protein analysis:

1. Retrieving protein sequences from different databases, either specialized or general databases and it is not an easy job if you would think so.
2. Computing a protein or amino acid sequence to obtain:

• So much of the physicochemical properties of you sequence like the molecular weight, and isoelectric point…etc
• Hydrophilicity / hydrophobicity ratio

Both of the above can provide us with the probabilities of one protein acting as a receptor on the cell surface or it might be antigenic or even secreted outside the cell.

3. On the prediction aspect, we can predict:

• Some sequences of certain importance, e.g. the prediction of signal peptides that can lead us to know the secretory proteins of one organism
• 2ry structure of your protein
• 3ry structure of your protein

The last two points are applications of what is called structural bioinformatics, through which computer is capable of predicting the 2ry and 3ry (3-D) configuration of your protein, using special programs with advanced algorithms and artificial intelligence. Amazingly, this may be useful in understanding the receptor-substrate interactions.

4. Comparing sequences to obtain the best alignment (it means compare 2 or more sequences to find their relation to each other, i.e. finding similarities and differences), it will help in:

• Classifying your protein and relate it to its protein family
• Making your evolutional expectations about your protein to define whether it descends from another protein or not. This is called phylogenetic analysis, at which the proteins under investigation are studied to know which protein is considered a mother to the others, which are the daughter, the grand daughter, and so on
• Detection of the common domains, this will help us understanding the functions of unknown protein when it is compared to sequences of other proteins of known functions

Then, what will we gain if we compute DNA? Or you can say, what can bioinformatics do for DNA research?

On the same level as with protein, though different applications, we can use it in:

• Retrieving DNA sequences from different databases
• Computing a sequence to obtain information about its properties (like proteins) e.g. GC% which could be used with other properties to identify a gene
• Assembling sequence fragments (usually DNA is sequenced in the form of fragments which are needed to be assembled in the best way, bioinfo. does this in a faster and more accurate way rather than the ordinary assembly)
• Designing a PCR primer
• Prediction of DNA and RNA secondary structures (e.g. prediction the stems and loops of the t-RNA)
• Performing alignments between 2 or more sequences that can lead to many applications (as those mentioned above in protein alignments)
• Finding of repeats, restriction sites, Single Nucleotide Polymorphism (SNPs), and/or open reading frames, all of which have so huge applications in the medical and paramedical fields and typically in the research activities.

   Send article as PDF to

Cancer: An abnormal uncontrolled proliferation of cells. The immune system doesn’t show any response, as the cancer cells are just some normal cells, which have gone crazy. That means that they could deceive our immune system, which recognizes them as normal.

The point of weakness

Cancer cells usually express so-called cancer-specific antigens, which are not otherwise expressed by normal cells.

The mission

Using these antigens as a method of differentiation, we have to teach our immune system to wipe out these cells without affecting the innocent normal ones.

How?

Whole cell vaccines: using tumor cells, derived from a patient or many patients or use human tumor cell lines designed in lab. This will elicit the immune response for all the antigens on cancer cells.

OR,

Antigen vaccines: using a specific antigen on the cancer cell through identifying a certain gene, then cloning the gene, which encodes for it.

Advancing

Adjuvants: using chemical substances to enhance T-cell response such as Interleukin-2 “IL2″.

Vector: using viral vectors to deliver the gene of interest to cells, which makes the cancer more visible to the immune system.

Major obstacle

One major obstacle facing cancer vaccines is that the response is not readily measurable. For chemotherapeutic drugs development, the end point is usually progression-free survival, which has shorter-term outcomes. Cancer vaccines are characterized by longer-term outcomes and increased survival rate.

For more information, Read here.

   Send article as PDF to