formerly a microbiology blog, this will now be a science blog, in which I post science only material. enjoy! p.s. I no longer teach microbiology, so I'm all out of original content, but reblogs will be plenty!
The Revolution in Prenatal Medicine
Prenatal medical testing has long been a balance of risk with information. Submit yourself to tests and you can find out about the genetic makeup of your future child, but risk miscarriage and other complications. Omit the tests, and a pregnancy is safer, its outcome uncertain.
That’s how it used to be, anyway. Now, genetic tests are becoming so cheap and non-invasive that they could become as routine as an ultrasound. DNA from the fetus is known to float freely in the mother’s blood and can be drawn in seconds, to be later analyzed for things like Down syndrome.
What will this mean for parents who discover birth defects or diseases in their unborn children? It’s impossible to know precisely who a child will become, but a world in which parents are informed of their baby’s genetics just weeks after conception brings with it a lot of ethical dilemmas.
Erin Biba analyzes this in one of the most interesting medical articles I’ve read in a long time, at Wired Science.
hm, sounds thought provoking and truly will cause a huge ethical dilemma with regards to how much do you really wanna know before the baby is even born.
Norovirus: The Human Pathogen That Turns Your Digestive System Into A Two-Way Firehose of Infection
Behold the humble norovirus. The humbly evil norovirus, one of the most perfect human pathogens. To be fair, viruses can’t be evil or not evil, they just want to reproduce. And how that happens to make their hosts feel is none of their concern. Noroviruses are masters of replication and infection, and they wreak havoc on the human digestive system in order to to their bidding.
That’s right. You know where this is going. Carl Zimmer reports, disgustingly:
Noroviruses come roaring out of the infected cells in vast numbers. And then they come roaring out of the body. Within a day of infection, noroviruses have rewired our digestive system so that stuff comes flying out from both ends.
How can a virus with just nine protein-coding genes do so much damage to a creature (us) with 20,000? Over a million people have come down with norovirus vomitorrhea in just the UK this winter.
These wee beasties replicate in the digestive system, waiting for you to “eject” them out of one end of your body. People who come in contact with the remnants of that “ejection”, even after cleaning, on planes or other crowded places, can be infected at alarming rates. Chances are it’s happened to you at some point in your life and you just called it a “stomach bug”.
Such a simple biological entity, refined by centuries upon centuries of molecular evolution, to exploit the digestive system of one class of mammals, reproducing in the safe warm home of our gut, and getting a free bi-directional rocket ride to their next host. Viruses never cease to amaze. And sometimes disgust.
Check out more on this virus from Carl Zimmer at Phenomena: The Loom.
‘Lady of the Cells’ Dead at 103
Italy has lost a truly fascinating centenarian. Nobel Prize winner Rita Levi-Montalcini died at her home yesterday at age 103, leading Rome’s mayor to declare the scientist’s death a loss “for all of humanity.” It may not be much of an exaggeration: The so-called “Lady of the Cells” faced many obstacles, reports the AP: a father who believed women should not study (she ultimately obtained a degree in medicine and surgery), a Fascist regime (Levi-Montalcini lost her neurobiology job in 1938 when Jews were banned from major professions), and the Nazis, whose 1943 invasion of Italy forced her family to flee to Florence and live underground.
But the petite woman’s determination was formidable: In the face of the Fascist regime she studied chicken embryos in a makeshift lab in her bedroom. She chose not to marry or have a family—without hesitation or regret, she once said—fearing doing so would weaken her independence. She claimed to sleep no more than three hours a night, and worked well into her final years. That effort produced contributions that were just as formidable.
Levi-Montalcini shared the Nobel medicine prize in 1986 with American biochemist Stanley Cohen for their groundbreaking cellular research. Her research increased the understanding of many conditions, including tumors, developmental malformations, and senile dementia.
(Image: AP Photo/Riccardo De Luca)
Another Muscular Dystrophy Mystery Solved; MU Scientists Inch Closer to a Therapy for Patients
Approximately 250,000 people in the United States suffer from muscular dystrophy, which occurs when damaged muscle tissue is replaced with fibrous, bony or fatty tissue and loses function. Three years ago, University of Missouri scientists found a molecular compound that is vital to curing the disease, but they didn’t know how to make the compound bind to the muscle cells. In a new study, published in the Proceedings of the National Academies of Science, MU School of Medicine scientists Yi Lai and Dongsheng Duan have discovered the missing pieces to this puzzle that could ultimately lead to a therapy and, potentially, a longer lifespan for patients suffering from the disease.
Duchenne muscular dystrophy (DMD), predominantly affecting males, is the most common type of muscular dystrophy. Patients with Duchenne muscular dystrophy have a gene mutation that disrupts the production of dystrophin, a protein essential for muscle cell survival and function. Absence of dystrophin starts a chain reaction that eventually leads to muscle cell degeneration and death. While dystrophin is vital for muscle development, the protein also needs several “helpers” to maintain the muscle tissue. One of these “helper” molecular compounds is nNOS, which produces nitric oxide that can keep muscle cells healthy after exercise.
“Dystrophin not only helps build muscle cells, it’s also a key factor to attracting nNOS to the muscles cells and helping nNOS bind to the cell and help repair it following activity,” said Lai, a research assistant professor in the Department of Molecular Microbiology and Immunology. “Prior to this discovery, we didn’t know how dystrophin made nNOS bind to the cells. What we found was that dystrophin has a special ‘claw’ that is used to grab nNOS and bring it close to the muscle cell. Now that we have that key, we hope to begin the process of developing a therapy for patients.”
(via neurosciencestuff)
Figure 2. Angiographie sélective de l’artère rénale gauche. Anévrisme à l’origine de l’artère segmentaire du pôle inférieur du rein gauche. Cette anévrisme présente un large collet et son diamètre est de 6 mm environ.
Figure 2. Left renal angiography showing an aneurysm at the segmental artery of the left kidney’s inferior pole. This aneurysm exhibits a large collar and a diameter of approximately 6 mm.
(via scinerds)
The Revolution in Prenatal Medicine
Prenatal medical testing has long been a balance of risk with information. Submit yourself to tests and you can find out about the genetic makeup of your future child, but risk miscarriage and other complications. Omit the tests, and a pregnancy is safer, its outcome uncertain.
That’s how it used to be, anyway. Now, genetic tests are becoming so cheap and non-invasive that they could become as routine as an ultrasound. DNA from the fetus is known to float freely in the mother’s blood and can be drawn in seconds, to be later analyzed for things like Down syndrome.
What will this mean for parents who discover birth defects or diseases in their unborn children? It’s impossible to know precisely who a child will become, but a world in which parents are informed of their baby’s genetics just weeks after conception brings with it a lot of ethical dilemmas.
Erin Biba analyzes this in one of the most interesting medical articles I’ve read in a long time, at Wired Science.
An x-ray micrograph of a yeast cell, Saccharomyces cerevisiae, as it buds before dividing. Courtesy of Carolyn Larabell, UC San Francisco, Lawrence Berkeley National Laboratory and the National Institute of General Medical Sciences.
In Epigenomics, Location is Everything
Researchers exploit gene position to test “histone code”
In a novel use of gene knockout technology, researchers at the University of California, San Diego School of Medicine tested the same gene inserted into 90 different locations in a yeast chromosome – and discovered that while the inserted gene never altered its surrounding chromatin landscape, differences in that immediate landscape measurably affected gene activity.
The findings, published online in the Jan. 3 issue of Cell Reports, demonstrate that regulation of chromatin – the combination of DNA and proteins that comprise a cell’s nucleus – is not governed by a uniform “histone code” but by specific interactions between chromatin and genetic factors.
“One of the main challenges of epigenetics has been to get a handle on how the position of a gene in chromatin affects its expression,” said senior author Trey Ideker, PhD, chief of the Division of Genetics in the School of Medicine and professor of bioengineering in UC San Diego’s Jacobs School of Engineering. “And one of the major elements of that research has been to look for a histone code, a general set of rules by which histones (proteins that fold and structure DNA inside the nucleus) bind to and affect genes.”
The Cell Reports findings indicate that there is no singular universal code, according to Ideker. Rather, the effect of epigenetics on gene expression or activity depends not only on the particular mix of histones and other epigenetic material, but also on the identity of the gene being expressed.
To show this, the researchers exploited an overlooked feature of an existing resource. The widely-used gene knockout library for yeast, originally created to see what happens when a particular gene is missing, was built by systematically inserting the same reporter gene into different locations. Ideker and colleagues focused on this reporter gene and observed what happens to gene expression at different locations along yeast chromosome 1.
“If epigenetics didn’t matter – the state of histones and DNA surrounding the gene – the expression of a gene would be the same regardless of where on the chromosome that gene is positioned,” said Ideker. But in every case, gene expression was measurably influenced by interaction with nearby epigenetic players.
Chronic myeloid leukemia blood cells.
Enzyme Accelerates Malignant Stem Cell Cloning in Chronic Myeloid Leukemia
An international team, headed by researchers at the University of California, San Diego School of Medicine, has identified a key enzyme in the reprogramming process that promotes malignant stem cell cloning and the growth of chronic myeloid leukemia (CML), a cancer of the blood and marrow that experts say is increasing in prevalence.
The findings are published in the Dec. 24 online early edition of the Proceedings of the National Academy of Sciences (PNAS).
Despite the emergence of new therapies, such as tyrosine kinase inhibitors, CML and other leukemias remain problematic because some cancer stem cells avoid destruction and eventually regenerate themselves, a stem cell process known as self-renewal that can result in a return and spread (metastasis) of the disease.
In the PNAS paper, principal investigator Catriona H. M. Jamieson, MD, PhD, associate professor of medicine at UC San Diego, with colleagues in the United States, Canada and Italy, report that inflammation – long associated with the development of cancer – boosts activity of an enzyme called adenosine deaminase or ADAR1.
Expressed during embryogenesis to help blood cell development, ADAR1 subsequently turns off and is triggered by viral infections where it protects normal hematopoietic stem cells from attack. In leukemia stem cells, however, overexpression of ADAR1 enhances the missplicing of RNA, which leads to greater self-renewal and therapeutic resistance of malignant stem cells.
The findings build upon previous studies by Jamieson and others that elucidate the effects of RNA missplicing and instability. “People normally think about DNA instability in cancer, but in this case, it’s how the RNA is edited by enzymes that really matters in terms of cancer stem cell generation and resistance to conventional therapy.”
The described RNA editing process, which occurs in the context of human and other primate specific sequences, also underscores the importance of addressing inflammation as “an essential driver of cancer relapse and therapeutic resistance,” Jamieson said. It also presents a new target for future therapies.
“ADAR1 is an enzyme that we may be able to specifically target with a small molecule inhibitor, an approach we have already used effectively with other inhibitors,” said Jamieson. “If we can block the capacity of leukemia stem cells to use ADAR1, if we can knock down that pathway, maybe we can put stem cells back on the right track and stop malignant cloning.”
CML is a cancer initiated by a mutant gene called BCR-ABL in blood forming stem cells that leads to an expansion of white blood cells and their precursors. It is typically slow-growing and often not diagnosed until its later stages when there can be a sudden, dramatic increase in malignant cells, known as blast crisis. Median age of diagnosis is 66 years; incidence of the disease increases with age. Despite tremendous advances in BCR-ABL tyrosine kinase inhibitor therapies, the majority of patients relapse if therapy is discontinued, in part as a result of dormant cancer stem cell resistance. This work suggests a novel mechanism for overcoming cancer stem cell resistance to therapy that may prevent relapse and progression.
The estimated prevalence of CML in the United States is 70,000 persons with the disease, projected to steadily increase to approximately 181,000 by 2050. CML is initiated by the mutant BCR-ABL gene, but scientists have not yet identified the cause of the mutation.
What Makes Cancer Cells Different?
We’ve talked before about how tricky a disease cancer is. Or, if you want to be accurate, how tricky a “set of diseases” it is. I mean, a single tumor is like a world unto itself, full of different populations of cells, each with their own individual set of mutations. That’s crazy to think about.
Cancer is the result of one of our cells’ most basic and core functions, cell division, gone awry. What causes it, in the large sense? How can we use cancer’s tricks against it to try and treat these diseases?
George Zaidan tackles those questions for TED-Ed in the video above. If nothing else, it’s the best combination of beans, fabric and cancer biology I’ve ever seen in a video. Goes nicely with my TED-Ed video on how the human genome is organized in the first place.
In Schizophrenia Patients, Auditory Cues Sound Bigger Problems
Researchers at the University of California, San Diego School of Medicine and the VA San Diego Healthcare System have found that deficiencies in the neural processing of simple auditory tones can evolve into a cascade of dysfunctional information processing across wide swaths of the brain in patients with schizophrenia.
The findings are published in the current online edition of the journal Neuroimage.
Schizophrenia is a mental disorder characterized by disturbed thought processes and difficulty in discerning real from unreal perceptions. Common symptoms include auditory hallucinations and unfounded suspicious ideas. The disorder affects about 1 percent of the U.S. population, or roughly 3 million people.
“Impairments in the early stages of sensory information processing are associated with a constellation of abnormalities in schizophrenia patients,” said Gregory Light, PhD, associate professor of psychiatry at UC San Diego and senior author of the study.
These impairments, according to Light, may explain how schizophrenia patients develop clinical symptoms such as hearing voices that others cannot hear and difficulty with cognitive tasks involving attention, learning and recalling information. “If someone’s brain is unable to efficiently detect subtle changes in sounds despite normal hearing, they may not be able to automatically direct their attention and rapidly encode new information as it is being presented.”
Light and colleagues used electroencephalography – a technique that records patterns of electrical brain activity using electrodes positioned on the scalp – on 410 schizophrenia patients and 247 nonpsychiatric comparison subjects. The researchers employed novel computational imaging approaches to deconstruct the brain dynamics that underlie two leading neurobiological markers used in schizophrenia research: mismatch negativity (MMN) and P3a event-related potentials.
