Alternative antibody architecture

The complex genomic apparatus for making lampreys' antibody-like receptors

The age of blood

Investigating how long blood can be stored before the benefit of transfusion is compromised

PTH for stroke: stem cells lite

Spur the body's regenerative agents to emerge from the bone marrow

Contraception and HIV risk

Does hormonal contraception increase the risk for a woman to acquire HIV from an infected partner?

This topic, with implications for public health in countries where HIV risk is high, has been contentious. Some previous studies had found the answer to be yes, for methods involving injectable progesterone such as Depo-Provera. This led the World Health Organization in 2012 to advise women using progesterone-only injections to use condoms to prevent HIV infection.

At the recent AIDS 2014 meeting in Australia, Emory epidemiologist Kristin Wall presented data from public health programs in Zambia. This is another study emerging from the Zambia-Emory HIV Research Project directed by Susan Allen.

Wall’s presentation is available here.

Studying 1393 heterosexual couples with a HIV-positive male partner over 17 years, Wall and her colleagues found no significant difference in incidence rate per 100 couple years between hormonal and non-hormonal forms of contraception. Read more

Posted on by Quinn Eastman in Immunology Leave a comment

Antibiotic resistance enzyme caught in the act

Resistance to an entire class of antibiotics – aminoglycosides — has the potential to spread to many types of bacteria, according to new biochemistry research.

A mobile gene called NpmA was discovered in E. coli bacteria isolated from a Japanese patient several years ago. Global spread of NpmA and related antibiotic resistance enzymes could disable an entire class of tools doctors use to fight serious or life-threatening infections.

Using X-ray crystallography, researchers at Emory made an atomic-scale snapshot of how the enzyme encoded by NpmA interacts with part of the ribosome, protein factories essential for all cells to function. NpmA imparts a tiny chemical change that makes the ribosome, and the bacteria, resistant to the drugs’ effects.

The results, published in PNAS, provide clues to the threat NpmA poses, but also reveal potential targets to develop drugs that could overcome resistance from this group of enzymes.

First author of the paper is postdoctoral fellow Jack Dunkle, PhD. Co-senior authors are assistant professor of biochemistry Christine Dunham, PhD and associate professor of biochemistry Graeme Conn, PhD. Read more

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Fighting HIV, biomedical and behavioral hand in hand

In the HIV/AIDS arena, the idea of “treatment as prevention” has been gaining strength. Multiple studies have shown that treatment with anti-retroviral drugs can dramatically reduce the likelihood that someone infected with HIV will be able to pass the virus to someone else.

However, a recent strategy document for HIV/AIDS prevention developed by a International Antiviral Society–USA panel, co-led by Rollins Global Health chair Carlos Del Rio, puts biomedical interventions hand in hand with psychosocial measures such as couples counseling and treatment for drug dependence.

Why? Because people everywhere can have trouble sticking to antiretroviral treatment, even if drugs are available. And couples counseling by itself is valuable.

A powerful example of how this plays out, and of the importance of couples counseling to the effectiveness of antiretroviral drugs in prevention, comes from a recent presentation from Emory epidemiologist Kristin Wall at the AIDS 2014 meeting in Australia. The website NAM Aidsmap had a helpful write-up of her presentation, which is available here. Thanks to co-author Susan Allen for alerting us to this.

CVCT (couples voluntary counseling and treatment) greatly enhanced the preventive effect of antiretroviral treatment, when compared to treatment without counselling, Wall’s analysis of a large cohort of couples in Zambia showed. 

Update: Allen points out that couples counseling by itself was effective in helping people avoid HIV, with a 75 percent reduction in incidence for couples where the HIV+ partner was not receiving antiviral therapy or with HIV negative couples.  Read more

Posted on by Quinn Eastman in Immunology 2 Comments

Socialization relative strength in fragile X longitudinal study

A study published in Pediatrics this week tracks “adaptive behavior” as children and adolescents with fragile X syndrome are growing up. This is the largest longitudinal study to date in fragile X, which is the leading inherited cause of intellectual disability and the leading single-gene risk factor for autism spectrum disorder.

Adaptive behavior covers a range of everyday social and practical skills, including communication, socialization, and completing tasks of daily living such as getting dressed. In this study, socialization emerged as a relative strength in boys with fragile X, in that it did not decline as much as the other two domains of adaptive behavior measured: communication and daily living skills.

The lead author of the paper is Cheryl Klaiman, formerly of the Stanford University Center for Interdisciplinary Brain Sciences, now senior psychologist at Marcus Autism Center.

The “socialization as relative strength in fragile X” findings meshes with a growing awareness in the autism field, summarized nicely here by Jessica Wright at the Simons Foundation Autism Research Initiative, that fragile X syndrome symptoms are often distinct from those in autism spectrum disorder.

One key distinction between the disorders, for example, is in social interactions. Children with autism and those with fragile X syndrome both shy away from social contact, have trouble making friends and avert their gaze when people look at them.

But children with fragile X syndrome often sneak a peek when the other person turns his back, researchers say. Children with autism, in contrast, seem mostly uninterested in social interactions.

“Children with fragile X syndrome all have very severe social anxiety that plays a big role in the perception that they have autism,” says Stephen Warren, professor of human genetics at Emory University School of Medicine in Atlanta. “They are actually interested in their environment; they are just very shy and anxious about it.”

Posted on by Quinn Eastman in Neuro Leave a comment

Debunking detour to DNA

Debunking the idea that most humans only use 10 percent of our brains, which is a starting point for the Scarlett Johansson/Luc Besson movie Lucy, was popular last week.
Many media outlets and popular Web sites took on this task. Emory’s Krish Sathian – known for his work on rehabilitation, how the brain processes sensory experiences and how we understand metaphors – does an able job of it in the video below.

But a related question is still a matter of debate: how much of our DNA do we “use”? This is an important question for geneticists because it seeks to define the most productive mutation hunting grounds.

A study published in PLOS Genetics last week concluded that just 8.2 percent of the human genome is constrained during evolution and is likely to be “functional”. The press release on this paper pointed out sharply that this contrasts with the more expansive analysis from the multinational ENCODE project, which assigned some biochemical function to 80 percent of the human genome.

Read more

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Anti-inflammatory drug prevents neuron loss in Parkinson’s model

A lot of evidence has piled up suggesting that inflammation plays a big role in the progression of Parkinson’s.

Immune system genes are linked to disease risk. People who regularly take NSAIDs such as ibuprofen have lower risk. Microglia, the immune system’s ambassadors to the brain, have been observed in PD patients.

Malu Tansey and her postdoc CJ Barnum make a convincing case for an anti-inflammatory — specifically, anti-TNF– therapy to Parkinson’s. They’ve been working with the Michael J. Fox Foundation for Parkinson’s Research to push this promising approach forward. Please check it out.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Potential anticancer drugs from humble sources

Jing Chen and colleagues at Winship Cancer Institute recently published a paper in Molecular CellMost of the paper deals with a metabolic enzyme, 6PGD (6-phosphogluconate dehydrogenase), and how it is more active in cancer cells.

Rhubarb_Flower

Rheum palmatum/Chinese rhubarb/da-huang

Tucked in at the end is a note that an inhibitor of 6GPD with an odd name, physcion, has anticancer activity in Chen’s team’s hands. Physcion, also known as parietin, is an orange-yellow pigment extractable from lichens and Chinese rhubarb that has been employed as an anti-mildew agent.

Probing cancer cells’ warped metabolism is a promising approach, for both drug discovery and finding effective ways to combine existing drugs, because of the Warburg effect: cancer cells’ tendency to suck up lots of sugar and use it in energy-inefficient ways. Read more

Posted on by Quinn Eastman in Cancer Leave a comment

Buzzword overuse alert: epigenetics

The term “epigenetics” has come up a lot here on the Lab Land blog.

In June a discussion came up on Twitter about scientific terms that are overused. I began to wonder whether I was contributing to the problem and may need to tighten up my use of the word “epigenetics.” Read more

Posted on by Quinn Eastman in Uncategorized Leave a comment

Making cardiac progenitor cells feel at home

One lab uses goopy alginate, another uses peptides that self-assemble into hydrogels. The objective is the same: protecting cells that are injected into the heart and making them feel like they’re at home.

Around the world, thousands of heart disease patients have been treated in clinical studies with some kind of cell-based therapy aimed at regenerating the heart muscle or at least promoting its healing. This approach is widely considered promising, but its effectiveness is limited in that most of the cells don’t stay in the heart or die soon after being introduced. [UPDATE: Nice overview of cardiac cell therapy controversy in July 18 Science]

Biomedical engineer Mike Davis and his colleagues recently published a paper in Biomaterials describing hydrogels that can encourage cardiac progenitor cells injected into the heart to stay in place. The first author is former graduate student Archana Boopathy, who recently started her postdoctoral work at MIT. Davis has been working with these self-assembling peptides for some time: see this 2005 Circulation paper he published during his own postdoctoral work with Richard Lee at Harvard.DavisDiagram

How do these hydrogels keep cells from washing away? We don’t have to go much beyond the name: think Jello. Researchers design snippets of proteins (peptides) that, like Jello*, form semisolid gels under the right conditions in solution. Helpfully, they also are customized with molecular tools for making cardiac progenitor cells happy. Read more

Posted on by Quinn Eastman in Heart 1 Comment

Rare disease diagnosis, accelerated by social media

Seth Mnookin’s long piece in the New Yorker, on how social media accelerated the diagnosis of several children with a rare genetic disorder, is getting a lot of praise this week. This is the same story that was on CNN.com in March, titled “Kids who don’t cry”, and that Emory Genetics Laboratory director Madhuri Hedge mentioned as a recent diagnostic success for the technique of whole exome sequencing.

Briefly: parents of or doctors treating several children with a previously unknown metabolic disorder, with multiple symptoms — absent tear production, developmental delay, movement deficits, digestive problems etc — found each other via Internet searches/blog posts. The problems were traced back to mutations in the NGLY1 gene.

Emory geneticists Michael Gambello, Melanie Jones (now at the Greenwood Genetic Center in South Carolina) and Hegde are co-authors on the Genetics in Medicine paper that lays everything out scientifically.

Gambello, Jones and Hegde were responsible for sequencing the DNA of a North Georgia family (they live in Jackson County), whose members are mentioned in Mnookin’s piece. The Gambello lab is developing an animal model of NGLY1 deficiency and is studying the mechanisms of how NGLY1 deficiency affects brain development.

Posted on by Quinn Eastman in Neuro Leave a comment
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