Archive for the ‘Biology and Medicine’ Category

WE HAVE MOVED!

June 10, 2012

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Neuroscientists reach major milestone in whole-brain circuit mapping

June 2, 2012

Neuroscientists at Cold Spring Harbor Laboratory (CSHL) reached a major milestone this week – publicly releasing the first data from their groundbreaking project, to construct the first whole-brain wiring diagram of a vertebrate brain, that of the mouse.

The data, which totals 500 terabytes, consists of gigapixel images (a billion pixels each) of whole-brain sections. These can be zoomed to show individual neurons and their processes, creating a “virtual microscope.” The images are integrated with other data sources from the web, and are being made fully accessible to neuroscientists as well as interested members of the general public (http://mouse.brainarchitecture.org). The data are being released pre-publication in the spirit of open science initiatives that have become familiar in digital astronomy (e.g. Sloan Digital Sky Survey) but are not yet as widespread in neurobiology.

A slice of the mouse brain. Click to enlarge.

Each sampled brain is represented in about 500 images, each image being an optical section through a 20 micron-thick slice of tissue. Users can journey through each brain from “front” to “back”, following the pathways taken through 3D brain space by tracer-labeled neuronal pathways. The tracers were picked to follow neuronal inputs and outputs of different brain regions.

“Our project seeks to address a remarkable gap in our knowledge of the brain,” says Partha Mitra, Professor of Biomathematics at CSHL and director of the Mouse Brain Architecture (MBA) Project.

“Our knowledge of how the brain is wired remains piecemeal and partial after a century of activity. To understand how the brain works (or fails to work in neurological disease), it is critical that we understand this wiring diagram more fully. Further, there remain fundamental questions about brain evolution that cannot be addressed without obtaining such wiring diagrams for the brains of different species.”

Projections from a motor cortex AAV injection (credit: CSHL)

The MBA Project is distinguished by the approach advocated by Mitra in a 2009 paper. Back then, Mitra proposed mapping vertebrate brains at what he described as the “mesoscopic” scale – a mid-range amenable to light microscopy, giving far more detail than MRI-based methods, yet considerably less detail than via electron microscopy (EM). The latter, while useful for mapping synaptic connections between individual neurons, is feasible on a whole-brain basis only for tiny brains (e.g. fruitflies) or very small portions of the mouse brain.

The pragmatic approach Mitra advocated, and which is realised in this first data release, is to image whole mouse brains in a semi-automated, quality-controlled process using light microscopy and injected neural tracers. While the basic methodology has been available for some time, systematically applying it to a grid of locations spanning the entire brain, and digitising/re-assembling the resulting collection of brains, is a new approach made feasible by the exponentially falling costs of computer storage. A mouse brain, at light-microscope resolution, generates around one terabyte (1000 GB) of data. Thus, producing and storing the data sets currently being gathered would have been impossibly expensive a decade or so ago.

“Our project is what I’d call a necessary first step in a much larger enterprise – that of understanding both structure and dynamics of the vertebrate, and ultimately, the human brain,” says Mitra.

Project highlights: http://brainarchitecture.org/mouse/highlights

Nokia Sensing X Challenge

May 30, 2012

The X PRIZE Foundation and Nokia have announced the launch of the Nokia Sensing X CHALLENGE – a $2.25 million global competition aimed at developing a new generation of health sensors and sensing technologies that can drastically improve the quality, accuracy and ease of monitoring a person’s health.

Improvements in these technologies will empower individuals to effortlessly monitor and collect their own real-time health data, providing both consumers and healthcare providers convenient access to critical information whenever and wherever they need it.

The announcement was made by X PRIZE Foundation Chairman and CEO Dr. Peter Diamandis and Nokia Executive Vice President and Chief Technology Officer Dr. Henry Tirri during their keynote address at the Wireless Health Convergence Summit in San Diego.

“Partnering with Nokia is a natural fit for this competition. Health sensing technologies enabled by artificial intelligence, lab-on-a-chip, and digital imaging are advancing exponentially and will ultimately integrate with your phone. We need to expand sensor and sensing technology beyond disease management to areas such as public health and fitness,” said Dr. Diamandis.

“The Nokia Sensing X CHALLENGE will bring about radical innovation in health sensors and sensing technologies, which paves the way for better choices in when, where, and how individuals receive care. Ultimately, healthcare will be more convenient, affordable, and accessible to consumers worldwide through these integrated digital health solutions.”

The inefficiencies and total cost of the U.S. healthcare system (and healthcare systems around the globe) has been a pressing social and political issue for many years. In the U.S., the total spent annually on the healthcare system is more than $2 trillion, which accounts for more than 15 percent of the nation’s GDP. Health sensors have the capacity to stem this trend. Consumer use of sensors and sensing solutions has the potential to improve, extend and ease delivery of healthcare services, as well as reduce costs to the benefit of health providers and patients.

“Nokia engages in Open Innovation on many different levels; this type of ‘grand challenge’ is not only a unique method of driving significant progress in a short space of time, but one which can also help to create an entire ecosystem,” said Dr. Tirri.

“This competition will enable us to realize the full potential of mobile sensing devices, leading to advances in sensing technology which can play a major role in transforming the lives of billions of people around the world.”

“Personality genes” may help account for longevity

May 29, 2012

“It’s in their genes” is a common refrain from scientists when asked what factors allow people to reach the age of 100 and beyond. Until now, research has focused on genetic variations that offer a physiological advantage like high levels of HDL (“good”) cholesterol.

But in a new study, researchers have found that personality traits – like being outgoing, optimistic, easygoing and enjoying laughter, as well as staying engaged in activities – may also help to produce extreme longevity.

The findings are published in the journal Aging, and come from Einstein’s Longevity Genes Project. This studied 500 Ashkenazi Jews, aged from 95 to 122, and their 700 offspring. Ashkenazi (Eastern European) Jews were selected because they are genetically homogeneous – making it easier to spot genetic differences within the group.

Previous studies have shown that personality arises from underlying genetic mechanisms directly affecting health. This new study was aimed at detecting genetically-based personality characteristics by developing a measure called the Personality Outlook Profile Scale (POPS).

“When I started working with centenarians, I thought we’d find they survived so long in part because they were mean and ornery,” said Nir Barzilai, director of Einstein’s Institute for Aging Research. “But when we assessed the personalities … we found qualities that clearly reflect a positive attitude towards life. Most were outgoing, optimistic and easygoing. They considered laughter an important part of life and had a large social network. They expressed emotions openly rather than bottling them up.”

In addition, the centenarians had lower scores for displaying neurotic personality and higher scores for being conscientious, compared with a representative sample of the U.S. population.

“Some evidence indicates that personality can change between the ages of 70 and 100, so we don’t know whether our centenarians have maintained their personality traits across their entire lifespans,” continued Dr. Barzilai. “Nevertheless, our findings suggest that centenarians share particular personality traits and genetically-based aspects of personality may play an important role in achieving both good health and exceptional longevity.”

Jet-injected drugs could mean the end of needles

May 26, 2012

Getting a shot at your doctor’s office may become less painful in the not-too-distant future.

MIT researchers have engineered a device that delivers a tiny, high-pressure jet of medicine through the skin without the use of a hypodermic needle. The device can be programmed to deliver a range of doses to various depths — an improvement over similar jet-injection systems that are now commercially available.

The researchers say that among other benefits, the technology may help reduce the potential for needle-stick injuries; the Centers for Disease Control and Prevention estimates that hospital-based health care workers accidentally prick themselves with needles 385,000 times each year. A needleless device may also help improve compliance among patients who might otherwise avoid the discomfort of injecting themselves with drugs such as insulin.

“If you are afraid of needles and have to frequently self-inject, compliance can be an issue,” says Catherine Hogan, a scientist in MIT’s Department of Mechanical Engineering and a member of the research team. “We think this kind of technology … gets around some of the phobias that people may have about needles.”

Hearts damaged by cardiac arrest could be repaired with stem cells

May 23, 2012

Israeli scientists have turned skin cells from heart failure patients into new, healthy heart muscle cells.

The study, which was published in the European Heart Journal, took skin cells from patients and re-programmed them to become stem cells capable of becoming heart muscle. They were then shown to integrate with existing heart tissue in rats.

This opens up the possibility of literally mending broken hearts. Since the reprogrammed cells would be obtained directly from the patients themselves, it could also avoid the problem of their immune systems rejecting the cells as “foreign.”

Professor Lior Gepstein, who led the research, said: “What is new and exciting about our research is that we have shown that it’s possible to take skin cells from an elderly patient with advanced heart failure and end up with his own beating cells in a laboratory dish that are healthy and young – the equivalent to the stage of his heart cells when he was just born.”

However, the team warns that there are a number of obstacles to overcome before it would be possible to use stem cells in humans in this way, and it could take 5-10 years before clinical trials begin.

This is nevertheless an important breakthrough, and the procedure may eventually help countless people who survive heart attacks but are severely debilitated by damage to the organ.

First gene therapy against aging is successful: mouse lifespan extended by 24% with a single treatment

May 15, 2012

Studies have shown it is possible to lengthen the average lifespan of many species, including mammals, by acting on specific genes. To date, however, this has meant altering genes permanently from the embryonic stage – an approach impracticable in humans.

Now, researchers at the Spanish National Cancer Research Centre (CNIO), led by its director María Blasco, have demonstrated that the mouse lifespan can be extended in adult life by a single treatment acting directly on the animal’s genes. And they have done so using gene therapy, a strategy never before employed to combat aging. This therapy has been found to be safe and effective in mice.

The results are published in the journal EMBO Molecular Medicine. The CNIO team, in collaboration with scientists from the Universitat Autònoma de Barcelona (UAB), treated adult (one year old) and aged (two year old) mice, with gene therapy delivering a “rejuvenating” effect in both cases, according to the authors.

Mice treated at the age of one lived longer by 24% on average, and those treated at the age of two, by 13%. Furthermore, the therapy produced a significant improvement in the animals’ health – delaying the onset of age-­related diseases like osteoporosis and insulin resistance – and improving their neuromuscular coordination.

The gene therapy itself treated mice with a DNA-­modified virus, the viral genes replaced by those of a telomerase enzyme with a key role in aging. Telomerase repairs the tips of chromosomes, known as telomeres, and in doing so slows the cell’s and therefore the body’s biological clock. When the animal is infected, the virus acts as a vehicle depositing the telomerase gene in the cells.

This study proves “it is possible to develop a telomerase-­based anti-­aging gene therapy without increasing the incidence of cancer,” the authors affirm. “Aged organisms accumulate damage in their DNA due to telomere shortening. [This study] finds that a gene therapy based on telomerase production can repair or delay this kind of damage,” they add.

Telomeres are the “caps” that protect the end of chromosomes, but they cannot do so indefinitely: each time the cell divides the telomeres get shorter, until they are so short that they lose all functionality. The cell, as a result, stops dividing and ages or dies. Telomerase gets around this by preventing telomeres from shortening or even rebuilding them. What it does, in essence, is stop or reset the cell’s biological clock.

But in most cells the telomerase gene is only active before birth; the cells of an adult organism, with few exceptions, have no telomerase. The exceptions in question are adult stem cells and cancer cells, which divide limitlessly and are therefore immortal – several studies have, in fact, shown that telomerase expression is the key to the immortality of tumour cells.

It is precisely this risk of tumour development that has set back the investigation of telomerase-based anti-aging therapies.

In 2007, Blasco’s group demonstrated that it was feasible to prolong the lives of transgenic mice, whose genome had been permanently altered at the embryonic stage, by causing their cells to express telomerase and extra copies of cancer-resistant genes. These animals lived 40% longer, without developing cancer.

Mice given the new gene therapy now under test are likewise free of cancer. Researchers believe this is because the therapy begins when the animals are adult, so do not have time to accumulate sufficient numbers of abnormal divisions for tumours to appear.

Bosch also states: “Because the vector we use expresses the target gene (telomerase) over a long period, we were able to apply a single treatment. This might be the only practical solution for an anti-aging therapy, since other strategies would require the drug to be administered over the patient’s lifetime, multiplying the risk of adverse effects.”

A potential new treatment for obesity

May 8, 2012

In mammals, there are two types of fat cells – brown and white. Brown fat expends energy, white fat stores it. The latter increases your risk of diabetes and heart disease, and the danger is especially linked to visceral fat. Visceral fat is the build-up of fat around the organs in the belly. So in the battle against obesity, brown fat appears to be our friend and white fat our foe.

Now a team of scientists at Brigham and Women’s Hospital and Harvard Medical School has discovered how to turn foe into friend. By manipulating the metabolic pathways in the body responsible for converting vitamin A – or retinol – into retinoic acid, they have essentially made white fat take on characteristics of brown fat.

The researchers found that inhibiting the Aldh1a1 gene by injecting antisense molecules into mice (made fat by diet) resulted in less visceral fat, less weight gain, and lower glucose levels compared to control mice.

Their findings bring science a step closer to developing potential new treatments for obesity. The full results of the study are published in Nature Medicine.

Aged stem cells rejuvenated to be functionally younger

May 6, 2012

Scientists have rejuvenated aged hematopoietic stem cells to be functionally younger, offering intriguing clues into how medicine might one day prevent some aspects of old age.

Researchers at Cincinnati Children’s Hospital Medical Center and the Ulm University Medicine in Germany report their findings online in the journal Cell Stem Cell. This study overturns what used to be a broad consensus – that the aging of hematopoietic stem cells (HSCs) was locked in by nature and impossible to reverse.

HSCs are stem cells that originate in the bone marrow and generate all of the body’s red and white blood cells and platelets. They are an essential support mechanism of blood cells and the immune system. As humans and other species age, HSCs become more numerous, but less effective at regenerating blood cells and immune cells. This makes older people more susceptible to infections and disease, including leukemia.

Researchers in the current study determined a protein that regulates cell signaling – Cdc42 – also controls a molecular process that causes HSCs from mice to age. Inhibition of Cdc42 reversed HSC aging and restored function similar to that of young stem cells according to Hartmut Geiger, the study’s lead investigator.

“Aging is interesting, in part because we still don’t understand how we age,” Geiger said. “Our findings suggest a novel and important role for Cdc42 and identify its activity as a target for ameliorating natural HSC aging. We know the aging of HSCs reduces in part the response of the immune system response in older people, which contributes to diseases such as anemia, and may be the cause of tissue attrition in certain systems of the body.”

The findings are early and involve lab manipulation of mouse cells, so it remains to be seen what direct application they may have for human beings. Still, the study expands what is known about the molecular and cellular mechanisms of aging – a necessary step on the long road to defeating the process.

These images of flouresced cells (which illuminate structural and functional components) illustrate the difference between young and aged hematopoietic stem cells. Younger cells have proteins grouped together in a concentrated and organised fashion, while the components of aged cells are more disorganised and scattered.

Could stem cells cure AIDS?

April 15, 2012

Expanding on previous research (providing proof-of-principle that human stem cells can be genetically engineered into fighting HIV), a team of UCLA researchers has now demonstrated that these cells can actually attack HIV-infected cells in a living organism.

The study, published in the 12th April journal PLoS Pathogens, demonstrates for the first time that engineering stem cells to form immune cells that target HIV is effective in suppressing the virus in living tissues in an animal model.

“We believe this study lays the groundwork for the potential use of this type of an approach in combating HIV infection in infected individuals, in the hope of eradicating the virus from the body,” says lead investigator Scott Kitchen, assistant professor at UCLA and a member of the UCLA AIDS Institute.

In previous research, scientists took CD8 cytotoxic T lymphocytes — the “killer” T cells that help fight infection — from an HIV-infected individual and identified the T cell receptor, which guides the T cell in recognizing and killing HIV-infected cells. However, these T cells, while able to destroy HIV-infected cells, do not exist in high enough quantity to clear the virus from the body. So the researchers cloned the receptor, using this to genetically engineer human blood stem cells. They then placed the engineered stem cells into human thymus tissue that had been implanted in mice, allowing them to study the reaction in a living organism.

The engineered stem cells developed into a large population of mature, multi-functional HIV-specific CD8 cells that could specifically target cells containing HIV proteins. The researchers also discovered that HIV-specific T cell receptors have to be matched to an individual in much the same way an organ is matched to a transplant patient.

In this current study, the researchers similarly engineered human blood stem cells and found that they can form mature T cells that can attack HIV in tissues where the virus resides and replicates. They did so by using a surrogate model — the humanised mouse — in which HIV infection closely resembles the disease and its progression in humans.

HIV virus (click to enlarge)

In a series of tests on the mice’s peripheral blood, plasma and organs conducted two weeks and six weeks after introducing the engineered cells, the researchers found that the number of CD4 “helper” T cells — which are depleted by HIV infection — increased, while levels of HIV in the blood decreased. CD4 cells are white blood cells that are a vital part of the immune system, helping to fight off infections. These results indicated that the engineered cells were able to develop and migrate to the organs to fight infection there.

The researchers did note a potential weakness with the study: Human immune cells reconstituted at a lower level in the humanised mice than they would in humans. As a result, the mice’s immune systems were mostly, though not completely, reconstructed. Because of this, HIV may be slower to mutate in the mice than in human hosts. So the use of multiple, engineered T cell receptors may be one way to adjust for the higher potential for HIV mutation in humans.

“We believe this is the first step in developing a more aggressive approach in correcting the defects in the human T cell responses that allow HIV to persist in infected people,” Kitchen said.

The researchers will now begin making T cell receptors that target different parts of HIV and that could be used in more genetically matched individuals, he said.