20090710-7

The-Scientist.com, June/July 2009, by Bob Grant  —  Scientists have elucidated a key element of how diet restriction might boost life span. A single pair of proteins, whose activity is linked to diminished food intake, is responsible for significantly increasing the lifespan of worms, a study published in this week’s Nature reports.

“[This study] is going to open a field that’s probably going to be important for mammalian life,” said gerontologist Nir Barzilai of the Albert Einstein College of Medicine in New York, who was not involved in the study. He cautioned that since the study was done in worms, its relevance to mammalian aging isn’t yet clear. “It’s not totally translatable, but it is exciting,” he said.

Scientists have been studying the phenomenon of increased longevity with diet restriction for about 70 years, and have replicated the effect in many species, from mice and fish to yeast and primates. But until about two years ago, when Andrew Dillin of the Salk Institute for Biological Studies in La Jolla and his team showed that a transcription factor called PHA-4 (or FOXA in humans) was involved, little of the genetic mechanism behind the lifespan benefit had been revealed. The present study, also from Dillin’s lab, elucidates upstream elements of the conserved pathway responsible for making diet restricted animals live longer. “It’s sort of like a ladder,” Dillin told The Scientist. “The bottom rung was FOXA, and now we’ve added on a few more rungs to the ladder.”

Most likely, caloric restriction causes longevity through some combination of genetic and environmental factors, with a reduced flow of nutrients into the body triggering genetic switches that lead to longer life, according to Barzilai. “Those are the switches [Dillin] is working on,” Barzilai told The Scientist. “What Dillin is doing here is connecting the interaction between genes and the environment” in Caenorhabditis elegans.

Dillin and his colleagues knew that eliminating a gene involved in protein degradation — wwp-1 — from the C. elegans genome resulted in adult worms that were more vulnerable to environmental stresses. This led them to suspect that the gene and the enzyme for which it coded — WWP-1 — might play a role in longevity. They showed that mutating WWP-1 in diet-restricted C. elegans could reduce the longer lifespans seen in diet restricted worms with normally functioning WWP-1. Preliminary studies suggested that another enzyme — UBC-18 — works in tandem with WWP-1 to produce this effect. “It was very surprising that this enzyme pair was so incredibly specific for the response to diet restriction,” said Dillin.

In humans, Dillin said, this enzyme pathway is conserved, so it may be possible to find compounds that alter the activity of these enzymes, essentially tricking the human body into thinking it is calorie-restricted under normal dietary conditions. That in turn could produce the longevity gains seen in calorie restricted individuals without the need for dieting. “WWP-1 and UBC-18 are both enzymes, so they give us good pharmacological targets to make small molecules to go after them,” said Dillin.

“You want to have some drug that will imitate caloric restriction, without us eating less,” Barzai said, calling Dillin’s findings “a natural step” towards this goal.

Dillin and his colleagues elicited this exact effect in normally-fed C. elegans when they over expressed WWP-1 and found that the worms lived 25% longer than normal.

Dillin’s lab is now searching for a receptor upstream of WWP-1 and UBC-18 that likely orchestrates the whole longevity/dietary-restriction pathway. His team is also searching for small molecules that target the two enzymes. “We may have some hints, but we don’t have any homeruns yet,” he said.

CDC Recommendations for State and Local Planning for a 2009 Novel H1N1 Influenza Vaccination Program

The purpose of this document is to describe planning scenarios for state and local governments to target high-priority populations for vaccination in order to reduce the health and societal impact of the novel H1N1 influenza virus.

Background

Data from U.S. and international sources suggests that it is appropriate to plan for a vaccination program to reduce the health and societal impacts of the novel H1N1 influenza virus.  In order to increase the probability of success of such a program, planning scenarios should be provided to state and local health authorities promptly.  Planning scenarios can facilitate readiness to implement specific plans within states and large cities, improving the chances that vaccine will reach target populations when recommendations are made, and that distribution, delivery, and communication efforts regarding vaccination will overcome local challenges and maximize capacities.  

Ongoing analysis through the summer of available data on the epidemiology and virologic characteristics of 2009-H1N1 virus and about vaccine efficacy will guide decisions about features of the program.  These decisions will be made in collaboration with expert panels and with input from the public.  For example, CDC’s Advisory Committee on Immunization Practices will provide specific vaccination recommendations, including specific target populations and priorities for circumstances of limited or phased vaccine supply.  In addition, the National Vaccine Advisory Committee will provide guidance on implementation and evaluation of vaccine safety.  A public engagement effort will also seek input from citizens from several regions around the country about these matters.  While additional data are collected and reviewed, state and local public health authorities need to accelerate their outreach to health care providers, the private sector, occupational groups, and others to put in place mechanisms and to develop vaccination venues appropriate to reach groups most likely to be included in a vaccination program against pandemic H1N1 influenza. 

Rationale Used in Developing the Planning Scenarios

The particular configuration of the vaccination program in each state and local jurisdiction will be determined by the population groups for which vaccine is recommended, and vaccination planning needs to encompass the diverse venues where vaccine might be delivered.  Identification of highly affected populations to date can highlight venues that need to be ready to administer vaccine to the various populations that might be included in the program, and provide the rationale for the planning scenarios.  Populations included in planning scenarios are based on the best current data to facilitate state and local planning.

Evidence to date suggests that population immunity to this virus is low, particularly among the young.  In one small serologic study of samples collected during 2006-08, cross-reacting antibody were found among some older persons but not in any younger adults or children.  Widespread susceptibility to this virus among young persons creates the potential for large numbers of cases with more hospitalizations and deaths among younger age groups than would be expected for a typical routine seasonal influenza virus. Importantly, severe disease and death caused by novel H1N1 thus far have affected younger adults, children, and pregnant women, in addition to persons of all ages with certain underlying medical conditions more than the elderly.  The virus has also caused numerous outbreaks in schools and summer camps.

Planning Assumptions

These planning scenarios are based on the following assumptions at the time vaccine becomes available and distribution begins:

  • 1. severity of illness is unchanged from what has already been observed
  • 2. risk groups affected by this virus do not change significantly
  • 3. vaccine testing suggests safe and efficacious product
  • 4. adequate supplies of vaccine can be produced
  • 5. no major antigenic changes are evident that would signal the lack of likely efficacy of the vaccines being produced

Planning Scenarios

The following are best-case planning scenarios that would be recommended in a setting of limited initial vaccine availability. 

Target population:  Students and staff (all ages) associated with schools (K-12th grade) and children (age ≥6 months) and staff (all ages) in child care centers. 

Primary venues:  schools and child care centers.
Goals:  Provide direct protection against illness among persons who have high attack rates of illness, reduce likelihood of outbreaks that may lead to disruptive school dismissals, reduce transmission from schools into homes and the community.

Adherence to these guidelines will require state and local authorities to carry out extensive planning to reach school-aged populations either through venues such as school-associated mass vaccination efforts, or, where private capacity is sufficient, through local pediatric providers.  Local pediatric care providers may play a particularly prominent role in vaccinating preschool-aged children who have a medical home.  These planning efforts will reinforce longer-term immunization targets of strengthening vaccination efforts in these populations, and building links between health and education.  The disruptive outbreaks prevalent in schools and some universities in the spring of 2009 may provide impetus for these planning steps to move forward actively.  They will also permit strengthening capacity for seasonal influenza vaccination of school-aged children in future seasons.

Target population: Pregnant women, children 6 months – 4 years of age, new parents and household contacts of children <6 months of age. 

Primary venues: Provider offices, community clinics.
Goal:  Reduce complications of novel H1N1 influenza, such as excess hospitalizations and deaths among those vulnerable for serious complications of influenza, as evidenced by higher rates of hospitalization; protect the youngest (<6 months) who are not themselves able to be vaccinated through immunization of their household contacts.

Sustaining a focus on pregnant women and young children is appropriate given their high rates of complications and hospitalizations to date, and is consistent with tier 1 prioritization for these groups in pre-pandemic planning.

Target population:  Non-elderly adults (age <65 years) with medical conditions that increase the risk of complications of influenza. 

Primary venues: Occupational settings, community clinics, pharmacies, providers’ offices.  (Experience with seasonal influenza vaccine suggests that persons with underlying illness age 50 to 64 years may be more likely to receive vaccine from their provider, while younger persons may be more likely to be vaccinated elsewhere).
Goal:  Reduce risk of hospitalizations and deaths among persons with higher rates of these complications than the general population, and focus vaccine where its impact can be most beneficial for direct protection. 

The planning requirement to offer vaccine to young adults with risk factors will permit state and local authorities to address a group that does not frequently seek health care and has relatively low rates of vaccination against seasonal influenza.  Links with occupational clinics, adult providers, or contingency plans for community venues or pharmacies are all options that might address this important at-risk group.

Target population:  Health care workers and emergency services sector personnel (regardless of age). 

Primary venue:  Occupational settings, providers’ offices.
Goal:  Reduce risk of illness, sustain health system functioning, and reduce absenteeism among front-line providers; reduce transmission from emergency services personnel and  health care workers to patients; provide additional worker protection in settings of increased exposure; reinforce importance of influenza vaccination among all health care workers.

Note:  Immunization of military (e.g., deployed forces) may be appropriate given the current circumstances; however, this memo focuses on vaccination of civilian populations under the authority of CDC and state and local health departments.

Vaccine Availability Considerations

If vaccine is widely available, CDC would recommend offering vaccine at multiple venues to anyone who wants to be vaccinated.  Although the benefits of vaccine may be greatest in the persons in groups at increased risk, and interest in being vaccinated may be lower among the general population, offering vaccine to everyone can reduce the risk of influenza for general population may reduce transmission to unvaccinated persons.  At the same time, if vaccine supply is limited, it will be important to consider a balance between international needs for vaccine in relation to the vaccination of low risk individuals in the United States.

adn_animation

The structure of part of a DNA double helix 

Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms and some viruses. The main role of DNA molecules is the long-term storage of information. DNA is often compared to a set of blueprints or a recipe, or a code, since it contains the instructions needed to construct other components of cells, such as proteins and RNA molecules. The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in regulating the use of this genetic information.

Chemically, DNA consists of two long polymers of simple units called nucleotides, with backbones made of sugars and phosphate groups joined by ester bonds. These two strands run in opposite directions to each other and are therefore anti-parallel. Attached to each sugar is one of four types of molecules called bases. It is the sequence of these four bases along the backbone that encodes information. This information is read using the genetic code, which specifies the sequence of the amino acids within proteins. The code is read by copying stretches of DNA into the related nucleic acid RNA, in a process called transcription.

Within cells, DNA is organized into X-shaped structures called chromosomes. These chromosomes are duplicated before cells divide, in a process called DNA replication. Eukaryotic organisms (animals, plants, fungi, and protists) store most of their DNA inside the cell nucleus and some of their DNA in the mitochondria (animals and plants) and chloroplasts (plants only)[1]. Prokaryotes (bacteria and archaea) however, store their DNA in the cell’s cytoplasm. Within the chromosomes, chromatin proteins such as histones compact and organize DNA. These compact structures guide the interactions between DNA and other proteins, helping control which parts of the DNA are transcribed.

GoogleNews.com, June/July 2009, by Sue Wuetcher  —  The concept of “personalized medicine” has gone from the traditional idea of a physician making a diagnosis and prescribing a medication to the next step: how the patient interacts with that medication once he or she starts taking it, Gene D. Morse, professor and associate dean for clinical and translational research in the School of Pharmacy and Pharmaceutical Sciences, told those attending yesterday’s inaugural lecture in this summer’s UBThisSummer lecture series.

As part of the FDA approval process for drugs, everyone participating in a clinical trial gets the same dosage of the same drug and “we really don’t have a very good way of figuring out who in this group will do well and who will not do well,” said Morse, whose lecture was titled “Personalized Medicine and Pharmacogenomics: Discovering New Genetic Methods to Link Diagnosis and Drug Treatment.”

Morse cited as an example a group of people who have high blood pressure and take a certain medication.

Some, he said, will take the medication and their blood pressure will go down and they will have no adverse side effects. Others will take the medication and their blood pressure will decline, but they will have serious adverse effects. And still others on the medication will continue to have high blood pressure, as well as the side effects.

“When you approach a group of individuals who are all on the same medication, we don’t know who’s going to have that response. So rather than the current system, which is trial and error, wouldn’t it be nice if we could predict which of these individuals would have different responses?” he asked.

He explained that the Human Genome Project has laid the groundwork for personalized medicine, determining the roadmap of our DNA and decoding the chromosomes down to the base players-the genes. Everyone has thousands of genes, and they vary from patient to patient, he said, adding that the technology now exists that can detect those differences in genes among large groups of people.

Morse said the research is starting to show that there are certain genetic tests that can be done to help determine how some medications will work in individuals based on their genetic makeup.

“If you can do that, then you can personalize things. You’ll have an idea what might happen when everybody gets the same medication,” he said. “Being able to predict this would be very useful.”

Researchers at UB and elsewhere are working with the DNA-the code for what proteins are made in the body-and the proteins, which define different functions of the cells.

“So if you can figure out what’s going in the DNA, then figure out which parts of the DNA encode, or send a message, for different proteins, you can actually begin to take what might be a population response (as in the high blood pressure example) and bring it down to an individual response. And that’s eventually what we’d like to be able to do.

“Understanding the DNA allows us to figure out why certain diseases make too much protein or why certain diseases don’t make enough protein,” he said.

20090708-1

Legend:
Illustration of the double helical structure of the DNA molecule.

The structure of DNA is illustrated by a right handed double helix, with about 10 nucleotide pairs per helical turn. Each spiral strand, composed of a sugar phosphate backbone and attached bases, is connected to a complementary strand by hydrogen bonding (non- covalent) between paired bases, adenine (A) with thymine (T) and guanine (G) with cytosine (C).

Adenine and thymine are connected by two hydrogen bonds (non-covalent) while guanine and cytosine are connected by three.

This structure was first described by James Watson and Francis Crick in 1953.

20090708-2

The double helix of the DNA is shown along with details of how the bases, sugars and phosphates connect to form the structure of the molecule.

DNA is a double-stranded molecule twisted into a helix (think of a spiral staircase). Each spiraling strand, comprised of a sugar-phosphate backbone and attached bases, is connected to a complementary strand by non-covalent hydrogen bonding between paired bases. The bases are adenine (A), thymine (T), cytosine (C) and guanine (G).

A and T are connected by two hydrogen bonds. G and C are connected by three hydrogen bonds.  

Comparative Scale of Mapping

20090708-3

Legend:

The relative mapping of cells, chromosomes and genes illustrated by comparing them to the relative mapping of features on Earth.

Developed by BSCS, in collaboration with the American Medical Association, under the United States Department of Energy Grant# DE-FGO2-91ER61147.

From:”Mapping and Sequencing the Human Genome: Science, Ethics, and Public Policy.” Developed by BSCS, in collaboration with the American Medical Association, under the United States Department of Energy Grant# DE-FGO2-91ER61147. 

Genes

20090708-4

Legend:
Illustration of the placement of genes in a chromosome.

 

A gene can be defined as a region of DNA that controls a hereditary characteristic. It usually corresponds to a sequence used in the production of a specific protein or RNA.

A gene carries biological information in a form that must be copied and transmitted from each cell to all its progeny. This includes the entire functional unit: coding DNA sequences, non-coding regulatory DNA sequences, and introns.

Genes can be as short as 1000 base pairs or as long as several hundred thousand base pairs. It can even be carried by more than one chromosome.

The estimate for the number of genes in humans has decreased as our knowledge has increased. As of 2001, humans are thought to have between 30,000 and 40,000 genes.

Gene

20090708-5

Chromosome

20090708-6

Biotechnology: Present and Future

20090708-7

Legend:
Areas of applied biotechnology:

In 1885, a scientist named Roux demonstrated embryonic chick cells could be kept alive outside an animal’s body. For the next hundred years, advances in cell tissue culture have provided fascinating glimpses into many different areas such as biological clocks and cancer therapy.

Monoclonal antibodies are new tools to detect and localize specific biological molecules. In principle, monoclonal antibodies can be made against any macromolecule and used to locate, purify or even potentially destroy a molecule as for example with anticancer drugs.

Molecular biology is useful in many fields. DNA technology is utilized in solving crimes. It also allows searchers to produce banks of DNA, RNA and proteins, while mapping the human genome. Tracers are used to synthesize specific DNA or RNA probes, essential to localizing sequences involved in genetic disorders.

With genetic engineering, new proteins are synthesized. They can be introduced into plants or animal genomes, producing a new type of disease resistant plants, capable of living in inhospitable environments (i.e. temperature and water extremes,…). When introduced into bacteria, these proteins have also produced new antibiotics and useful drugs.

Techniques of cloning generate  large quantities of pure human proteins, which are used to treat diseases like diabetes. In the future, a resource bank for rare human proteins or other molecules is a possibility. For instance, DNA sequences which are modified to correct a mutation, to increase the production of a specific protein or to produce a new type of protein can be stored . This technique will be probably play a key role in gene therapy.
 

Adapted from: BIO. “Biotechnology in Perspective.” Washington, D.C.: Biotechnology Industry Organization

Transgenic Mice

20090708-8

Legend:

Illustration of how transgenic mice are produced.

Genes responsible for particular traits or disease susceptibility are chosen and extracted. Next they are injected into fertilized mouse eggs. Embryos are implanted in the uterus of a surrogate mother. The selected genes will be expressed by some of the offspring.

Since the first gene transfers into mice were successfully executed in 1980, transgenic mice have allowed researchers to observe experimentally what happens to an entire organism during the progression of a disease. Transgenic mice have become models for studying human diseases and their treatments. 

Construction of a Human Genomic Library

20090708-9

Human genomic libraries can be constructed using restriction nucleases and ligase. A genomic library comprises a set of bacteria, each carrying a different small fragment of human DNA. For simplicity, cloning of just a few representative fragments (colored) is shown. In reality, all the gray DNA fragments will also be cloned.

20090708-10

20090710-1

The Nike+ team – (from left) Trevor Edwards, Michael Tchao, and Stefan Olander – at the company’s headquarters in Beaverton, Oregon.
Image: Kate Gibb

Wired.com, June/July 2009, by Mark McClusky  —  On June 6, 2008, Veronica Noone attached a small sensor to her running shoes and headed out the door. She pressed start on her iPod and began keeping track of every step she took. It wasn’t a long run-just 1.67 miles in 18 minutes and 36 seconds, but it was the start of something very big for her., emblazoned with Nike’s iconic Swoosh logo, sits on the conference room table at the company’s headquarters in Beaverton, Oregon. It’s a clunky thing, the size of a thick paperback book, with a waist strap and two ports on the front that look like miniature speakers, lending it the air of a shrunken mid-’80s boom box.

Since that day, she’s run 95 more times, logging 283.8 miles in about 48 hours on the road. She’s burned 28,672 calories. And her weight, which topped 225 pounds when she was pregnant, has settled in at about 145.

Noone knows all of that thanks to the sensor system, called Nike+. After each run, she can sync her iPod to the Nike+ Web site and get a visual representation of the workout-a single green line. Its length shows how far she’s gone, and the peaks and valleys reflect her speed.

For a self-described “stat whore,” there’s something powerfully motivating about all the data that Nike+ collects. “It just made running so much more entertaining for me,” says Noone, who blogs at ronisweigh.com. “There’s something about seeing what you’ve done, how your pace changes as you go up and down hills, that made me more motivated.”

Noone is now running four times a week and just did her first 10-mile race. She’s training for a half marathon and hoping to do a full marathon by the end of the year. And she attributes much of her newfound fitness to the power of data. “I can log in to Nike+ and see what I’ve done over the past year,” she says. “That’s really powerful for me. When I started, I was running shorter and slower. But I can see that progression. I don’t have to question what I’ve done. The data is right there in white and green.”

Noone has joined the legion of people, from Olympic-level athletes to ordinary folks just hoping to lower their blood pressure, who are plugging into a data-driven revolution. And it goes way beyond Nike+. Using a flood of new tools and technologies, each of us now has the ability to easily collect granular information about our lives-what we eat, how much we sleep, when our mood changes.

And not only can we collect that data, we can analyze it as well, looking for patterns, information that might help us change both the quality and the length of our lives. We can live longer and better by applying, on a personal scale, the same quantitative mindset that powers Google and medical research. Call it Living by Numbers-the ability to gather and analyze data about yourself, setting up a feedback loop that we can use to upgrade our lives, from better health to better habits to better performance.

Few things illustrate the power and promise of Living by Numbers quite as clearly as the Nike+ system. By combining a dead-simple way to amass data with tools to use and share it, Nike has attracted the largest community of runners ever assembled-more than 1.2 million runners who have collectively tracked more than 130 million miles and burned more than 13 billion calories.

20090710-3 

There is a vast universe of personal metrics to capture. Start with these:

Vital Statistics
height // weight // age // birth weight // birth length

20090710-4 

Vital Signs
body temperature // pulse // blood pressure // respiratory rate

20090710-5 

Senses
visual acuity // auditory acuity

20090710-6 

Blood
glucose level // blood-alcohol level // hemoglobin level // HDL level // LDL level // liver enzyme level

With such a huge group, Nike is learning things we’ve never known before. In the winter, people in the US run more often than those in Europe and Africa, but for shorter distances. The average duration of a run worldwide is 35 minutes, and the most popular Nike+ Powersong, which runners can set to give them extra motivation, is “Pump It” by the Black Eyed Peas.

The company couldn’t have gathered all that information, and gained all those insights, if it hadn’t reconfigured how runners approach their sport. Nike has done more than create a successful product; it has fundamentally changed the way more than a million people think about exercise.

A brown plastic box

It was called the Nike Monitor, and it was the company’s first attempt to sell runners a product that would tell them how far and fast they had run. The ports on the front weren’t speakers-they were sonar detectors that would calculate a runner’s speed, which would then be announced over a pair of headphones. The Monitor had to be strapped to the runner’s waist facing forward. It may have been a good idea, but it was utterly impractical. Less than two years after its 1987 launch, the Monitor was dropped from Nike’s product lineup.

How Nike+ Works

20090710-2