Queen of Decay

The January 2009 issue of Science has an article about Osedax, an annelid worm with help from Oceanospirillales bacteria, feeds on the bones of whales. 

It notes how the male worms are parasitic on females and "thus fertilization is guaranteed." 

The females from a swimming trochophore [A trochophore is a type of free-swimming planktonic marine larva with several bands of cilia] only occurs when the larvae encounter a carcass and have been infected with the endosymbiont. 

Interestingly enough there is an article in the December 2008 edition of National Geographics about Pilosaurs, that were big as school buses and looks like precursors to whales. They lived in the Jurassic Period, were 50-feet-long and found 400 million miles from Norway's Coast. I would bet that Oceanospirillales feasted on these and had plenty of time to diversify to adjust around the world. 

FoldIt and Education

The January 2009 edition of Science Magazine chronicles Steven Pletsch who, with his infant daughter in his lap, learned the protein folding game Foldit, helped team of university graduate students win a biochemistry competition. 

Pletsch spent up to 30 hours a week with the game learning the fundamentals of protein folding. He has no background or degree and is a self-taught designer of low-voltage electrical devices. 

Once again, the non-college educated has more insight than the mass trained.

lincRNAs Discovered in Genome

A new study finds about 1,600 known highly conserved, long RNAs with important regulatory roles in the mammlian genome. These are non-protein coding genes that produce "large intervening non-coding RNAs or lincRNAs." 

[There functions include the] regulate a variety of different cellular processes, including cell proliferation, immune surveillance, maintenance of embryonic stem cell pluripotency, neuronal and muscle development, and gametogenesis.

This is in contrast to the nearly 20,000 protein encoding genes. This will add to the classic examples of RNA such as microRNAs. 

People Don't Respect Herpes

'“Mono probably doesn’t have the respect it deserves,” said Dr. Robert Frenck..“It is a significant disease in the U.S., and people trivialize it,” [Dr. Joseph Pagano] said.' 95 percent of people become infected with Epstein-Barr, the herpes virus that causes mononucleosis. Spytoms include "fatigue, fever, sore throats, swollen glands and an enlarged spleen...[even] serious complications in transplant patients or those with weakened immune systems."

Overuse of Sleeping Pills

The use of sleeping pills has tripled in use amongst those of college-age, "rising from 599 users per 100,000 in 1998 to 1,524 users per 100,000 in 2006. Dr. Eric M. Plakun ...said the increasing reliance on sleeping pills reflects changes in cultural attitudes toward medication use."

This is a generation that was raised on Ritalin and Adderall," Dr. Plakun said. "They and their parents have turned to medication and found medications can be helpful. But it’s a double-edged sword. You pay a price in which taking a pill becomes the way to go.

Ritalin (methylphenidate) is used to treat ADHD, narcolepsy, daytime fatigue. It was patented in 1954. It is a central nervous stimulant produced by Novartis.

Novartis has about 18 small molecule drugs on the market.

Study links water pollution with declining male fertility

More medicine and hormones in our tap water. New research by Dr Susan Jobling at Brunel University and the University of Exeter has shown how "female sex hormones (estrogens), and chemicals that mimic estrogens, are leading to ‘feminisation’ of male fish."

“We have been working intensively in this field for over ten years. The new research findings ... effects seen in wild fish and in humans are caused by similar combinations of chemicals. We have identified a new group of chemicals in our study on fish, but do not know where they are coming from.”

'Professor Charles Tyler of the University of Exeter said: ”Our research shows that a much wider range of chemicals than we previously thought is leading to hormone disruption in fish. This means that the pollutants causing these problems are likely to be coming from a wide variety of sources. Our findings also strengthen the argument for the cocktail of chemicals in our water leading to hormone disruption in fish, and contributing to the rise in male reproductive problems. There are likely to be many reasons behind the rise in male fertility problems in humans, but these findings could reveal one, previously unknown, factor.”'

Our microbes, ourselves

It is becoming very clear that obesity is not caused by the weak-willed or McDonalds per say. It is becoming more clear that hormones and genetic predisposition is far more important. Take for instance gut microbes, that may well be the lead actor telling the person what to eat.

A new article notes that there is a "link between differing microbial populations in the human gut and body weight among three distinct groups: normal weight individuals, those who have undergone gastric bypass surgery, and patients suffering the condition of morbid obesity..."

What is living in your gut may well be dictating what you feel like eating.

Dr. John DiBaise, a gastroenterologist at the Mayo Clinic, Arizona, Bruce Rittmann, Ph.D., an environmental engineer and a member of National Academy of Engineering, Rosa Krajmalnik-Brown, assistant professor of civil and environmental engineering all worked on this study.

The team look at 16S rRNA, molecular structure which provides a characteristic fingerprint for microbial identification.
The team used:
454-pyrosequencing, which allows a significantly larger number and greater diversity of gut microbia to be identified.

"The resulting composition of gut microbiota in the three gastric bypass patients differed substantially...the microbial populations extracted from obese individuals were high in a particular microbial subgroup, hydrogen-producing bacteria known as prevotellaceae."

"Further, such hydrogen producers appear to coexist with hydrogen-consuming methanogens, found in abundance in obese patients, but absent in both normal weight and gastric bypass samples."

This is really amazing. This means that a certain bacteria appears only when you are obese. Not when you are not, or not any more.


"Organisms producing hydrogen and acetate create a situation like cars flooding onto the highway. The methanogens, which remove the hydrogen, are like the offramps, allowing the hydrogen cars to get off. That allows more acetate cars to get on, because some hydrogen cars are coming off the highway."

The bacteria that consumes the hydrogen and acetate are present only in the overweight. So that must mean that hydrogen and acetate must exist, and that the bacteria that consume it causes, via by their presence or by-product, the obesity.

Here is where is gets interesting.

"The methanogen offramps, by removing hydrogen, accelerate the efficient fermentation of otherwise indigestible plant polysaccharides and carbohydrates. The effect is to boost production of SCFAs, particularly acetate, which will be taken up by the intestinal epithelium and converted to fat. The result over time may be increasing weight, eventually leading to obesity."

Compounds in Tap Water

The Southern Nevada Water District tested water in 19 different counties for 51 different compounds and discovered 11 compounds existing at low levels. They include drugs like beta-blockers, herbicide, hormones, tranquilisers, and anti-biotics. They list goes as...

• Atenolol, a beta-blocker used to treat cardiovascular disease

• Atrazine, an organic herbicide banned in the European Union, but still used in the US, which has been implicated in the decline of fish stocks and in changes in animal behaviour

• Carbamazepine, a mood-stabilising drug used to treat bipolar disorder, amongst other things

• Estrone, an oestrogen hormone secreted by the ovaries and blamed forcausing gender-bending changes in fish

• Gemfibrozil, an anti-cholesterol drug

• Meprobamate, a tranquiliser widely used in psychiatric treatment

• Naproxen, a painkiller and anti-inflammatory linked to increases in asthma incidence

• Phenytoin, an anticonvulsant that has been used to treat epilepsy

• Sulfamethoxazole, an antibiotic used against the Streptococcus bacteria, which is responsible for tonsillitis and other diseases

• TCEP, a reducing agent used in molecular biology

• Trimethoprim, another antibiotic

Doctor's Error

"A new study has found that hospitals could cut surgery complications by about 30 percent and resulting deaths by 40 percent if doctors and nurses follow a checklist of safety rules before, during and after performing surgery."

The World Health Organization wants to implement this list of 19 steps to take from observations from about 7,688 patients. 234 million majors surgeries are performed every year around the world.

Neutralizing Ebola

Ebola is probably the world's most deadly virus, but its mode of entry is still probably the same as any virus. To understand how to cure ebola might require the ability to detect the virus in our bodies and produce effective antibodies. Research has found a key protein known as VP35. VP35 interfered with the natural resistance of the host cell against viral infection. How, it doesn't say. But, now that they have the protein's structure, the one that interferes with the immune system, they can now design a drug. Without VP35, ebola cannot replicate. 

RNA World Model

Which came first, DNA or RNA? DNA carries the genetic sequence for advanced organisms, while RNA is dependent. 

"The scientists have synthesized for the first time RNA enzymes that can replicate themselves without the help of any proteins or other cellular components, and the process proceeds indefinitely."

"But one prominent theory about the origins of life, called the RNA World model, postulates that because RNA can function as both a gene and an enzyme, RNA might have come before DNA and protein and acted as the ancestral molecule of life."

"The goal was to take one of the RNA enzymes already developed in the lab that could perform the basic chemistry of replication, and improve it to the point that it could drive efficient, perpetual self-replication."

Here is an interesting enzyme model...

"The replicating system actually involves two enzymes, each composed of two subunits and each functioning as a catalyst that assembles the other. The replication process is cyclic, in that the first enzyme binds the two subunits that comprise the second enzyme and joins them to make a new copy of the second enzyme; while the second enzyme similarly binds and joins the two subunits that comprise the first enzyme. In this way the two enzymes assemble each other — what is termed cross-replication. To make the process proceed indefinitely requires only a small starting amount of the two enzymes and a steady supply of the subunits."

""This is the only case outside biology where molecular information has been immortalized," says Joyce."

"He is quick to point out that, while the self-replicating RNA enzyme systems share certain characteristics of life, they are not themselves a form of life."

Do White Blood cells Make Cancer Deadly?

The American Scientist has an article by Charles Q. Choi about the documented events of cancer fusing with macrophages to increase metastasis. Dermatologist John Pawelek oberserved that cancer cells possibly fuse with macrophages to all

ow it to travel to other parts of the body. He sites Otto Aichel 1911 experiments and reenforces his belief with the work of Lynn Margulis Endosymbiotic Theory. 

Some people:

Bert Vogelstein - Genetics, Cancer Research

Lynn Margulis - Endosymbiotic Theory

Circadian Oscillator

Structural Insights into a Circadian Oscillator
Science 31 October 2008 p697

This particular piece concerns the structures and components by which cells keep time. It is not necessarily time as much as rhythmic milestones.

Endogenous (produced from growth of deep tissue) circadian system in cyanobacteria control processes. A circadian rhythm is by definition endogendous and refers to a roughly 24 hour cycle. This machinery can be reconstructed just with proteins KaiA, KaiB, and KaiC. They work through conformational changes and phosphorylation (of what). The mechanism can be deduced as a racheting mechanism and ticks unidirectionally.

Biological processes are dictated by daily, self-sustaining circadian clocks of 24 hour cycles. They show a difference for day and night mediated by dark and light cycles to phase with the environment.

The study concerned prokaryotic cyanobacterium Synechoccus elongates. The rhythm conforms optimally to the daily cycle, including photosynthesis, nitrogen fixation, and gene expression.

This study used competition assays that are…

Any competition assay takes advantage of the fact that that some
signal you can measure depends on the _total_ concentration of
substance. Thus, by introducing a range of _known_ amounts of that
substance and therefore _diluting_ the same substance present in the
sample at unknown concentration, one can extract the number in the
sample.

that demostrate that this clock system significantly enhanced the fitness of the cells in rhythmic environments, but not in non-selective environments.

Clocks have been seen to influence:
- the topology of the entire cyanobacterial chromosome
- the superhelical status of DNA, such as large scale torsion that modulates transcription rates. Therefore, gene-expression patterns are mediated by caily changes in the topology of the gene.
- The chromosome might be envisioned as an oscillating nucleoid that regulates all promoter.
- KaiABC controls the phosphorylation status of RpaA that is a down transcriptional regulator. This is the SasA/RpaA two-component system mediating signals from KaiABC.

Thioredoxin- Thioredoxins are proteins that act as antioxidants by facilitating the reduction of other proteins by cysteine thiol-disulfide exchange.

Phosporylation occurs on the serine and theronine.

Triclosan

Triclosan is the most common chemical in antibacterial products. Genetic mutations can arise in bacteria exposed to triclosan. Triclosan and its close chemical relative triclocarban have been found in 60% of US streams and rivers (Rolf Halden-John Hopkins Bloomberg School of Public Health). Triclosan has been found in human breast milk and blood plasma. It can comprise the hormone system. Scientific American Februaru 200 8 page 96.Triclosan is alcohol soluable and is comprised of phenols, which have antibacterial properties. It is a biocide, with cytoplasm and membrane targets.

Neutrophil Follow-up

There are three types of white blood cells: Granulocytes, Monocytes, and Lymphocytes. 

Neutrophils are a type of granulocyte that is also called polymorphonuclear leucocyte. They are the most common. They phagocytose and destroy microorganisms -especially bacteria. 

The other types of granulocytes are the basophil - that secrete histamine and mediate inflammatory reactions and eosinophils that destroy parasites.

Monocytes mature into macrophages. Macrophages and Neutrophils make up the main phagocytes in the body.

Neutrophil Soldiers or Trojan Horses?

Science 

15 August 2008

p917

We know that biting insects transmits viral, bacterial, and parasitic infections. We do not know the initial events that occur as pathogens are introduced by these vectors into the wounds. It is under investigation that early events in vector mediated injury influence the outcome of sandfly-transmitted parasite Leishmania major. 

Neutrophils are the first wave of inflammatory cells that migrate into these sites. They have phagocytic actions are regarded as foot solders armed with oxygen radicals, lytic enzymes, and cationic proteins. Unfortunetly, they are short lived. Their corpes are phagocytosed by macrophages. L. major internalizes by entering neurophils and become phagocytosed. 

This was possible with transgenic mice with fluorescent neutrophils and deep tissue immaging. 

Was the phagocytic events independent of sand fly bite and L. major internalization? Yes, because they discovered that by injecting beads, a similar accumulation event of neutrophils occured. 

Does any interfere with neutrophils accumulate?  Tissue damage was proposed as an alternative that overrid the effect of sandfly bite. But sustained recruitment was observed compared with less from just a needle stick. 

Most cells that contained L. major were neutrophils after 18 hours. (So there was a time dependance)

and soon after most cells that had L. major were macrophages in 6 to seven days. 

What was unexpected was that instead of engulfing dying infected neutrophils, macrophages acquired the parasites that had been released from neutrophils undergoing apoptosis. 

BUT, macrophages were not predominant, others were: interleukin-1. Since there was an absence of neutrophils, it hindered the ability to infect macrophages. 

An alternative mechanism is that parasites are better adapted to survive in macrophages. (?)

Dendritic cells and Langerhans cells are important to transport the parasite to lymph nodes. 

Most parasites die in the neutrophil by oxidative burst. 

The Trojan Horse theory is also applicable to Ehrlichia and Francisella tularensis.

Beena John and Christopher A. Hunter

University of Pennsylvania Vet Med

What I Learned

Infections can have a model of entry

The Trojan Horse Theory - Immune cells can care infection

Because something happens (neutrophil recruitment) it might not lead to the next step (macrophage recruitment). Paradoxically, it leads to other recruitment but a less infection. 

Just because something should do something (phagocytose) it might not.

What are the Questions I Learned

Every Step needs another explaination. Neutrophils accumlate at wound site, infection or not. 

What interfers with accumlation? Possible tissue damage.

What are the things that can hinder the steps?