Neural Cell News Volume 5.03 | Jan 26 2011

TOP STORY

Conversion of Brain Tumor Cells into Blood Vessels Thwarts Treatment Efforts 
When faced with a life-threatening oxygen shortage, glioblastoma cells can shift gears and morph into blood vessels to ensure the continued supply of nutrients, reports a study. [Press release from the Salk Institute for Biological Studies discussing online prepublication in the Proceedings of the National Academy of Sciences USA]

SPECIAL FEATURE

A Very Sad Loss – Stem Cell Pioneer Ernest A. McCulloch Passes Away
It is with great sadness that scientists honour the life and extraordinary contributions of Dr. Ernest “Bun” McCulloch who passed away on Wednesday, January 19th, 2011. Dr. McCulloch, along with his close friend and colleague, Dr. James Till, was a pioneer in the field of stem cell research. [Canadian Stem Cell Foundation Press Release]

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Deubiquitylase HAUSP Stabilizes REST and Promotes Maintenance of Neural Progenitor Cells
The repressor element 1-silencing transcription factor (REST) functions as a master regulator to maintain neural stem/progenitor cells (NPCs). REST undergoes proteasomal degradation through beta-TrCP-mediated ubiquitylation during neuronal differentiation. However, reciprocal mechanisms that stabilize REST in NPCs are undefined. Here researchers show that the deubiquitylase HAUSP counterbalances REST ubiquitylation and prevents NPC differentiation. [Nat Cell Biol]

Alpha-Synuclein Propagates from Mouse Brain to Grafted Dopaminergic Neurons and Seeds Aggregation in Cultured Human Cells
Post-mortem analyses of brains from patients with Parkinson disease who received fetal mesencephalic transplants show that alpha-synuclein-containing (alpha-syn-containing) Lewy bodies gradually appear in grafted neurons. Here, researchers explored whether intercellular transfer of alpha-syn from host to graft, followed by seeding of alpha-syn aggregation in recipient neurons, can contribute to this phenomenon. [J Clin Invest]

Ephaptic Coupling of Cortical Neurons
The extent to which such ephaptic coupling alters the functioning of neurons under physiological conditions remains unclear. To address this question, researchers stimulated and recorded from rat cortical pyramidal neurons in slices with a 12-electrode setup. [Nat Neurosci]

Calmodulin as a Direct Detector of Ca2+ Signals
Researchers have determined the rate at which Ca2+ binds to calmodulin (CaM) and found that Ca2+ binds more rapidly to CaM than to other Ca2+-binding proteins. This property of CaM and its high concentration support a new view of signal transduction: CaM directly intercepts incoming Ca2+ and sets the free Ca2+ level (that is, it strongly contributes to fast Ca2+ buffering) rather than responding to the lower Ca2+ level set by other buffers. [Nat Neurosci]

Transdifferentiation of Glioblastoma Cells into Vascular Endothelial Cells
To assess the resistance mechanism to anti-VEGF therapy, researchers examined the vessels of glioblastomas in tumors that were induced by the transduction of p53+/- heterozygous mice with lentiviral vectors containing oncogenes and the marker GFP in the hippocampus of GFAP-Cre recombinase (Cre) mice. [Proc Natl Acad Sci USA]

Repression of Puma by Scratch2 is Required for Neuronal Survival during Embryonic Development
Data indicate that the regulatory loop linking p53/Puma with Scratch is active in the vertebrate nervous system, not only controlling cell death in response to damage but also during normal embryonic development. [Cell Death Differ]

Multipotent Adult Progenitor Cells Prevent Macrophage-Mediated Axonal Dieback and Promote Regrowth after Spinal Cord Injury
Using an in vitro model of axonal dieback as well as an adult rat dorsal column crush model of spinal cord injury, researchers found that multipotent adult progenitor cells (MAPCs) can affect both macrophages and dystrophic neurons simultaneously. [J Neurosci]

A Reduction in ATP Demand and Mitochondrial Activity with Neural Differentiation of Human Embryonic Stem Cells
Although stem cells collectively in vivo might be expected to rely primarily on anaerobic glycolysis for ATP supply, to minimise production of reactive oxygen species, researchers show that in vitro this is not so: human embryonic stem cells (hESCs) generate an estimated 77% of their ATP through oxidative phosphorylation. Upon differentiation of hESCs into neural stem cells, oxidative phosphorylation declines both in absolute rate and in importance relative to glycolysis. [J Cell Sci]

Determination of Somatic and Cancer Stem Cell Self-Renewing Symmetric Division Rate Using Sphere Assays
The neurosphere assay represents a method to detect the presence of neural stem cells, however owing to a deficiency of specific and definitive markers to identify them, their quantification and the rate they expand is still indefinite. Here researchers propose a mathematical interpretation of the neurosphere assay allowing actual measurement of neural stem cell symmetric division frequency. [PLoS ONE]

BrainStorm Appoints Dr. Adrian Harel as Chief Operating Officer and Acting Chief Executive Officer
BrainStorm Cell Therapeutics Inc., a leading developer of adult stem cell technologies and therapeutics, announced the recruitment of a highly experienced drug developer, Adrian Harel, Ph.D., as its Chief Operating Officer and Acting Chief Executive Officer. [Brainstorm Cell Therapeutics, Inc. Press Release]

New SFU Surrey Lab Targets Biomedical Research
Research in Sparrey’s lab will target the biomechanics of tissue degeneration and the effect of aging on brain and spinal cord injury susceptibility. [Simon Fraser University Press Release]

Repligen Licenses Rights to Use of HDAC3 Inhibitors for Memory Disorders
Repligen Corporation announced that it has entered into an exclusive license agreement with the University of California, Irvine (UCI) for a patent application covering the use of histone deacetylase 3 (HDAC3) inhibitors for the treatment of disorders involving preservation or extinction of memory including Alzheimer’s disease, memory impairment and post traumatic stress disorder. [Repligen Corporation Press Release]

Targacept Announces Positive Top-Line Results from Phase 2 Trial of TC-5619 in Cognitive Dysfunction in Schizophrenia
Targacept, Inc. announced positive top-line results from a Phase 2 clinical proof of concept trial to assess TC-5619 as an augmentation therapy to improve cognition in patients with schizophrenia. [Targacept, Inc. Press Release]

Research Leaders Move Forward
On January 21, the Canada Foundation for Innovation (CFI) announced it has awarded $1,332,798 to eight University of Manitoba researchers who are working on a variety of projects, enabling them to improve our knowledge of the world and continue to lead in their field. [University of Manitoba Press Release]

National Institutes of Health (United States)

Food and Drug Administration (United States)

Center for Biologics Evaluation and Research (United States)

European Medicines Agency (European Union)

Medicines and Healthcare Products Regulatory Agency (United Kingdom)

Therapeutic Goods Administration (Australia)

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