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The expression “once bitten, twice shy” is an illustration of how a bad experience can induce fear and caution. How to effectively reduce the memory of aversive events is a fundamental question in neuroscience. Scientists in China are reporting that by transplanting mouse embryonic interneurons into the brains of mice and combining that procedure with training to lessen fear, they can help to reduce the fear response. The study is being published December 8 in Neuron.

“Anxiety and fear-related disorders such as post-traumatic stress disorder [PTSD] cause great suffering and impose high costs to society,” says Yong-Chun Yu, a professor at the Institutes of Brain Science at Fudan University in Shanghai and the study’s senior author. “Pharmacological and behavioral treatments of PTSD can reduce symptoms, but many people tend to relapse. There’s a pressing need for new strategies to treat these refractory cases.”

Continue reading “Transplanted interneurons can help reduce fear in mice” »

A new study finds that having a single extra chromosome may reduce the chance of cancerous tumors. But like everything, it’s a balancing act.

Gene therapy techniques were used to insert a peptide into cultures of human cancer cells that blocked their ability to use the enzyme Hypoxia-inducible factor-1, a heterodimeric transcription factor that enables cell survival under low oxygen conditions by altering the transcription of over 300 genes.

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival, and progression of tumors. There is significant evidence that inhibition of HIF-1 would be beneficial for cancer therapy, since tumor cells must thrive in a microenvironment characterized by lack of oxygen. In previous work, investigators at the University of Southampton (United Kingdom) discovered a cyclic hexapeptide (cyclo-CLLFVY) that inhibited the HIF-1alpha/HIF-1beta protein–protein interaction in vitro and prevented HIF-1-mediated hypoxia-response signaling in cells. This cyclic peptide was identified by screening a library that contained more than 3.2 million compounds.

With a view to demonstrating the potential for encoding the production of a therapeutic agent in response to a disease marker, the investigators engineered human cells with an additional chromosomal control circuit that conditionally encoded the production of the cyclic peptide HIF-1 inhibitor. They then demonstrated the conditional production of the HIF-1 inhibitor in response to hypoxia, and its inhibitory effect on HIF-1 dimerization and downstream hypoxia-response signaling.

Continue reading “Gene Therapy Prevents Cancer Cells from Surviving in Hypoxic Environment” »

Synthetic Biology Diabetes mellitus affects hundreds of millions of people worldwide. Blood glucose levels are chronically deregulated in diabetics, and this can lead to many serious disorders, including cardiovascular disease and renal failure. Xie et al. engineered a synthetic circuit into human.

A severely brain injured woman, who recovered the ability to communicate using her left eye, restored connections and function of the areas of her brain responsible for producing expressive language and responding to human speech, according to new research from Weill Cornell Medicine scientists.

The study, published Dec. 7 in Science Translational Medicine, began 21 months after Margaret Worthen suffered massive strokes, and her continuing recovery was tracked for nearly three years. The research signifies the first time that scientists have captured the restoration of communication of a minimally conscious patient by measuring aspects of brain structure and function before and after communication resumed. It also raises the question of whether other patients in chronic care facilities who appear to be minimally responsive or unresponsive may harbor organized, higher-level brain function.

“From the beginning of Margaret’s attempt to communicate, through the course of our study, we were able to show reorganization of the areas of her brain responsible for expressive language, as well as an exceptionally large change in the correlation across the brain areas in response to human speech,” said study lead author Daniel Thengone, the Fred Plum Fellow in Systems Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute at Weill Cornell Medicine. Adds senior study author Dr. Nicholas D. Schiff, the Jerold B. Katz Professor of Neurology and Neuroscience in the Feil Family Brain and Mind Research Institute: “This is a unique demonstration of plastic change in the brain of an adult starting years after a severe brain injury. We showed a convergence of measurements over years and at multiple time points, revealing an evolving biological process of recovery.”

Precise stimulation could be useful for visual prosthetics or brain-computer interfaces.

In the George Lucas classic Star Wars, hero Luke Skywalker’s arm is severed and amputated during a lightsaber fight and consequently fitted with a bionic arm that he can use as if it were his own limb. At the time the script was written, such a remedy was pure science fiction; however, the ability to manufacture bionic arms that have the functionality and even feel of a natural limb is becoming very real, with goals of launching a prototype as soon as 2009. Already, primates have been trained to feed themselves using a robotic arm merely by thinking about it, while brain sensors have been picking up their brain-signal patterns since 2003. The time has come for implementing this technology on paralyzed human patients and amputees. This article will provide a brief explanation of the technology, its current status, and the potential future it holds.

A new way to destroy and replace the immune system without harsh chemo or radiation could be the path to fixing immunosenescence.

Destroying and replacing the aging immune system could help with a host of age-related problems as well as autoimmune diseases. Radiation or Chemo were previously the only options which carries significant risks. With this new technique and a few others currently being developed we may soon have a way to replace aging dysfunctional immune systems and treating diseases like MS to boot.

#aging #crowdfundthecure

Continue reading “Withholding amino acid depletes blood stem cells” »

FightAging! interviews Mantas from CellAge about their campaign on Lifespan.io / Life Extension Advocacy Foundation and talks about senolytics and synthetic biology.

I mentioned CellAge some weeks ago; a new entry to the collection of companies and research groups interested in developing the means to safely identify and remove senescent cells from old tissues. A few days later one of those companies, UNITY Biotechnology, announced a sizable $116 million venture round, which certainly put the field on the map for anyone who wasn’t paying attention up until that point. In contrast, CellAge are determinedly taking the non-profit route, and intend to make the progress they create freely available to the field. Why are senescent cells important? Because they are a cause of aging, and removing them is a narrowly focused form of rejuvenation, shown to restore function and extend healthy life in animal studies. An increasing number of senescent cells linger in our bodies as we age, secreting signals that harm tissue structures, produce chronic inflammation, and alter the behavior of nearby cells for the worse. Senescent cells also participate more directly in some disease processes, such as the growth of fatty deposits, weakening and blocking blood vessels, that takes place in atherosclerosis. By the time that senescent cells come to make up 1% of the cell population in an organ, their presence causes noticeable dysfunction and contributes significantly to the progression of all of the common age-related diseases.

This coming Monday, the CellAge team will be hosting an /r/futurology AMA event — the post is up already if you want add your own questions for the scientists involved. Earlier this week, the CellAge principals launched a crowdfunding campaign with Lifespan.io: they are seeking $40,000 with stretch goals and rewards beyond that to get started on their vision for senescent cell therapies. If you’ve ever wanted the chance to have a DNA promoter sequence named after you … well, here it is. This has certainly been a busy year for community fundraising in rejuvenation research: I imagine that things will heat up even more in the years ahead. The CellAge view of the field of senescent cell clearance is that the markers currently used to identify senescent cells are too crude and lacking in specificity.

Continue reading “An Interview with Mantas Matjusaitis of CellAge, Crowdfunding New Senescent Cell Markers and Removal Methodologies” »