Oh Yeah, Developmental Biology!

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neurosciencestuff:

A new weapon against stroke
UC Davis stem cell study uncovers the brain-protective powers of astrocytes
One of regenerative medicine’s greatest goals is to develop new treatments for stroke. So far, stem cell research for the disease has focused on developing therapeutic neurons — the primary movers of electrical impulses in the brain — to repair tissue damaged when oxygen to the brain is limited by a blood clot or break in a vessel. New UC Davis research, however, shows that other cells may be better suited for the task.
Published today in the journal Nature Communications, the large, collaborative study found that astrocytes — neural cells that transport key nutrients and form the blood-brain barrier — can protect brain tissue and reduce disability due to stroke and other ischemic brain disorders.
“Astrocytes are often considered just ‘housekeeping’ cells because of their supportive roles to neurons, but they’re actually much more sophisticated,” said Wenbin Deng, associate professor of biochemistry and molecular medicine at UC Davis and senior author of the study. “They are critical to several brain functions and are believed to protect neurons from injury and death. They are not excitable cells like neurons and are easier to harness. We wanted to explore their potential in treating neurological disorders, beginning with stroke.”
Deng added that the therapeutic potential of astrocytes has not been investigated in this context, since making them at the purity levels necessary for stem cell therapies is challenging. In addition, the specific types of astrocytes linked with protecting and repairing brain injuries were not well understood.
The team began by using a transcription factor (a protein that turns on genes) known as Olig2 to differentiate human embryonic stem cells into astrocytes. This approach generated a previously undiscovered type of astrocyte called Olig2PC-Astros. More importantly, it produced those astrocytes at almost 100 percent purity.
The researchers then compared the effects of Olig2PC-Astros, another type of astrocyte called NPC-Astros and no treatment whatsoever on three groups of rats with ischemic brain injuries. The rats transplanted with Olig2PC-Astros experienced superior neuroprotection together with higher levels of brain-derived neurotrophic factor (BDNF), a protein associated with nerve growth and survival.  The rats transplanted with NPC-Astros or that received no treatment showed much higher levels of neuronal loss.
To determine whether the astrocytes impacted behavior, the researchers used a water maze to measure the rats’ learning and memory. In the maze, the rats were required to use memory rather than vision to reach a destination. When tested 14 days after transplantation, the rats receiving Olig2PC-Astros navigated the maze in significantly less time than the rats that received NPC-Astros or no treatment.
The investigators used cell culture experiments to determine whether the astrocytes could protect neurons from oxidative stress, which plays a significant role in brain injury following stroke. They exposed neurons co-cultured with both types of astrocytes to hydrogen peroxide to replicate oxidative stress. They found that, while both types of astrocytes provided protection, the Olig2PC-Astros had greater antioxidant effects. Further investigation showed that the Olig2PC-Astros had higher levels of the protein Nrf2, which increased antioxidant activity in the mouse neurons.
“We were surprised and delighted to find that the Olig2PC-Astros protected neurons from oxidative stress in addition to rebuilding the neural circuits that improved learning and memory,” said Deng.
The investigators also investigated the genetic qualities of the newly identified astrocytes. Global microarray studies showed they were genetically similar to the standard NPC-Astros. The Olig2PC-Astros, however, expressed more genes (such as BDNF and vasoactive endothelial growth factor, or VEGF) associated with neuroprotection. Many of these genes help regulate the formation and function of synapses, which carry signals between neurons.
Additional experiments showed that both the Olig2PC-Astros and NPC-Astros accelerated synapse development in mouse neurons. The Olig2PC-Astros, however, had significantly greater protective effects over the NPC-Astros.
In addition to being therapeutically helpful, the Olig2PC-Astros showed no tumor formation, remained in brain areas where they were transplanted and did not differentiate into other cell types, such as neurons.
“Dr. Deng’s team has shown that this new method for deriving astrocytes from embryonic stem cells creates a cell population that is more pure and functionally superior to the standard method for astrocyte derivation,” said Jan Nolta, director of the UC Davis Institute for Regenerative Cures. “The functional improvement seen in the brain injury models is impressive, as are the higher levels of BDNF. I will be excited to see this work extended to other brain disease models such as Huntington’s disease and others, where it is known that BDNF has a positive effect.”
Deng added that the results could lead to stem cell treatments for many neurodegenerative diseases.
“By creating a highly purified population of astrocytes and showing both their therapeutic benefits and safety, we open up the possibility of using these cells to restore brain function for conditions such as Alzheimer’s disease, epilepsy, traumatic brain disorder, cerebral palsy and spinal cord injury,” said Deng.

neurosciencestuff:

A new weapon against stroke

UC Davis stem cell study uncovers the brain-protective powers of astrocytes

One of regenerative medicine’s greatest goals is to develop new treatments for stroke. So far, stem cell research for the disease has focused on developing therapeutic neurons — the primary movers of electrical impulses in the brain — to repair tissue damaged when oxygen to the brain is limited by a blood clot or break in a vessel. New UC Davis research, however, shows that other cells may be better suited for the task.

Published today in the journal Nature Communications, the large, collaborative study found that astrocytes — neural cells that transport key nutrients and form the blood-brain barrier — can protect brain tissue and reduce disability due to stroke and other ischemic brain disorders.

“Astrocytes are often considered just ‘housekeeping’ cells because of their supportive roles to neurons, but they’re actually much more sophisticated,” said Wenbin Deng, associate professor of biochemistry and molecular medicine at UC Davis and senior author of the study. “They are critical to several brain functions and are believed to protect neurons from injury and death. They are not excitable cells like neurons and are easier to harness. We wanted to explore their potential in treating neurological disorders, beginning with stroke.”

Deng added that the therapeutic potential of astrocytes has not been investigated in this context, since making them at the purity levels necessary for stem cell therapies is challenging. In addition, the specific types of astrocytes linked with protecting and repairing brain injuries were not well understood.

The team began by using a transcription factor (a protein that turns on genes) known as Olig2 to differentiate human embryonic stem cells into astrocytes. This approach generated a previously undiscovered type of astrocyte called Olig2PC-Astros. More importantly, it produced those astrocytes at almost 100 percent purity.

The researchers then compared the effects of Olig2PC-Astros, another type of astrocyte called NPC-Astros and no treatment whatsoever on three groups of rats with ischemic brain injuries. The rats transplanted with Olig2PC-Astros experienced superior neuroprotection together with higher levels of brain-derived neurotrophic factor (BDNF), a protein associated with nerve growth and survival.  The rats transplanted with NPC-Astros or that received no treatment showed much higher levels of neuronal loss.

To determine whether the astrocytes impacted behavior, the researchers used a water maze to measure the rats’ learning and memory. In the maze, the rats were required to use memory rather than vision to reach a destination. When tested 14 days after transplantation, the rats receiving Olig2PC-Astros navigated the maze in significantly less time than the rats that received NPC-Astros or no treatment.

The investigators used cell culture experiments to determine whether the astrocytes could protect neurons from oxidative stress, which plays a significant role in brain injury following stroke. They exposed neurons co-cultured with both types of astrocytes to hydrogen peroxide to replicate oxidative stress. They found that, while both types of astrocytes provided protection, the Olig2PC-Astros had greater antioxidant effects. Further investigation showed that the Olig2PC-Astros had higher levels of the protein Nrf2, which increased antioxidant activity in the mouse neurons.

“We were surprised and delighted to find that the Olig2PC-Astros protected neurons from oxidative stress in addition to rebuilding the neural circuits that improved learning and memory,” said Deng.

The investigators also investigated the genetic qualities of the newly identified astrocytes. Global microarray studies showed they were genetically similar to the standard NPC-Astros. The Olig2PC-Astros, however, expressed more genes (such as BDNF and vasoactive endothelial growth factor, or VEGF) associated with neuroprotection. Many of these genes help regulate the formation and function of synapses, which carry signals between neurons.

Additional experiments showed that both the Olig2PC-Astros and NPC-Astros accelerated synapse development in mouse neurons. The Olig2PC-Astros, however, had significantly greater protective effects over the NPC-Astros.

In addition to being therapeutically helpful, the Olig2PC-Astros showed no tumor formation, remained in brain areas where they were transplanted and did not differentiate into other cell types, such as neurons.

“Dr. Deng’s team has shown that this new method for deriving astrocytes from embryonic stem cells creates a cell population that is more pure and functionally superior to the standard method for astrocyte derivation,” said Jan Nolta, director of the UC Davis Institute for Regenerative Cures. “The functional improvement seen in the brain injury models is impressive, as are the higher levels of BDNF. I will be excited to see this work extended to other brain disease models such as Huntington’s disease and others, where it is known that BDNF has a positive effect.”

Deng added that the results could lead to stem cell treatments for many neurodegenerative diseases.

“By creating a highly purified population of astrocytes and showing both their therapeutic benefits and safety, we open up the possibility of using these cells to restore brain function for conditions such as Alzheimer’s disease, epilepsy, traumatic brain disorder, cerebral palsy and spinal cord injury,” said Deng.

Women in science: How can we plug the leaking pipeline? - 05 June 2013 - New Scientist

Baby dinos pumped their muscles inside the egg

currentsinbiology:


Sperm Replace the Germ

The physical location of many stem cell niches is difficult to identify, but in the Drosophila testis, the niche is easy to locate. At the tip of each testis is a cluster of nondividing cells called the hub (blue nuclei on left-hand side) with two populations of stem cells surrounding it: the male germline stem cells (green) give rise to interconnected spermatogonia, whereas the somatic cyst stem cells (bright red nuclei) produce cyst cells (faint red nuclei). The cyst cells envelope the germline cells throughout their differentiation and are analogous to Sertoli cells in mammals. Images such as this one have shown that clusters of interconnected spermatogonia can replace missing germline stem cells.
Image: A whole Drosophila testis is imaged with a laser scanning confocal microscope. A nuclear marker stains somatic cyst stem cells bright red, whereas it diminishes in their daughters. Germline stem cells and their progeny are marked green with a cortically localized GFP. DNA is blue. (Erika Matunis and Becca Sheng, Johns Hopkins University

currentsinbiology:

Sperm Replace the Germ

The physical location of many stem cell niches is difficult to identify, but in the Drosophila testis, the niche is easy to locate. At the tip of each testis is a cluster of nondividing cells called the hub (blue nuclei on left-hand side) with two populations of stem cells surrounding it: the male germline stem cells (green) give rise to interconnected spermatogonia, whereas the somatic cyst stem cells (bright red nuclei) produce cyst cells (faint red nuclei). The cyst cells envelope the germline cells throughout their differentiation and are analogous to Sertoli cells in mammals. Images such as this one have shown that clusters of interconnected spermatogonia can replace missing germline stem cells.

Image: A whole Drosophila testis is imaged with a laser scanning confocal microscope. A nuclear marker stains somatic cyst stem cells bright red, whereas it diminishes in their daughters. Germline stem cells and their progeny are marked green with a cortically localized GFP. DNA is blue. (Erika Matunis and Becca Sheng, Johns Hopkins University

heythereuniverse:

Mouse embryo, 10.5 days old | Alan Boyde

heythereuniverse:

Mouse embryo, 10.5 days old Alan Boyde

Jun 4

Lemon Shark: Sac to “Stem” 

Shown about halfway through its 12-month gestation period in a computer-generated illustration, a lemon shark—like a human embryo—is literally connected to its mother via an umbilical cord attached to a placenta. But it wasn’t always so.

Until about three months in the womb, baby sharks feed off a yolk sac. Once the embryo has depleted the yolk, the collapsed sac settles against the womb wall and shoots blood vessels into the wall, tapping into the mother’s circulatory system.

By the time the embryo is six months old (pictured), it has a sense of smell 10,000 times sharper than a human’s. This and other sensory adaptations—including electro-sensors that detect the faint voltage of other animals—will one day allow the shark to detect even a fin flick hundreds of feet away, according to the National Geographic documentary In the Womb: Extreme Animals.

From the National Geographic (US) and Channel 4 (UK) Documentary Animals in the womb.

Jun 2

The Brains of the Animal Kingdom - WSJ.com

fuckyeahneuroscience:

New research shows that we have grossly underestimated both the scope and the scale of animal intelligence. Primatologist Frans de Waal on memory-champ chimps, tool-using elephants and rats capable of empathy.

Who is smarter: a person or an ape? Well, it depends on the task. Consider Ayumu, a young male chimpanzee at Kyoto University who, in a 2007 study, put human memory to shame. Trained on a touch screen, Ayumu could recall a random series of nine numbers, from 1 to 9, and tap them in the right order, even though the numbers had been displayed for just a fraction of a second and then replaced with white squares.

I tried the task myself and could not keep track of more than five numbers—and I was given much more time than the brainy ape. In the study, Ayumu outperformed a group of university students by a wide margin. The next year, he took on the British memory champion Ben Pridmore and emerged the “chimpion.”

How do you give a chimp—or an elephant or an octopus or a horse—an IQ test? It may sound like the setup to a joke, but it is actually one of the thorniest questions facing science today. Over the past decade, researchers on animal cognition have come up with some ingenious solutions to the testing problem. Their findings have started to upend a view of humankind’s unique place in the universe that dates back at least to ancient Greece.

Jun 2

paleoillustration:

Baby rex by Spike Ekins:

“My rendition of Jun Huang´s Baby T. rex sculpt won both Best of Show and 1st place at two of Denmark´s biggest and best competitions for modelmakers a couple of years ago.

I would now add an insulatory coat of down if I could work out how best to do it”

I want it.

Jun 1

Down syndrome neurons grown from stem cells show signature problems

neurosciencestuff:

Down syndrome, the most common genetic form of intellectual disability, results from an extra copy of one chromosome. Although people with Down syndrome experience intellectual difficulties and other problems, scientists have had trouble identifying why that extra chromosome causes such widespread effects.

In new research published this week, Anita Bhattacharyya, a neuroscientist at the Waisman Center at UW-Madison, reports on brain cells that were grown from skin cells of individuals with Down syndrome.

“Even though Down syndrome is very common, it’s surprising how little we know about what goes wrong in the brain,” says Bhattacharyya. “These new cells provide a way to look at early brain development.”

The study began when those skin cells were transformed into induced pluripotent stem cells, which can be grown into any type of specialized cell. Bhattacharyya’s lab, working with Su-Chun Zhang and Jason Weick, then grew those stem cells into brain cells that could be studied in the lab.

One significant finding was a reduction in connections among the neurons, Bhattacharyya says. “They communicate less, are quieter. This is new, but it fits with what little we know about the Down syndrome brain.”  Brain cells communicate through connections called synapses, and the Down neurons had only about 60 percent of the usual number of synapses and synaptic activity. “This is enough to make a difference,” says Bhattacharyya. “Even if they recovered these synapses later on, you have missed this critical window of time during early development.”

The researchers looked at genes that were affected in the Down syndrome stem cells and neurons, and found that genes on the extra chromosome were increased 150 percent, consistent with the contribution of the extra chromosome.

However, the output of about 1,500 genes elsewhere in the genome was strongly affected. “It’s not surprising to see changes, but the genes that changed were surprising,” says Bhattacharyya. The predominant increase was seen in genes that respond to oxidative stress, which occurs when molecular fragments called free radicals damage a wide variety of tissues.

“We definitely found a high level of oxidative stress in the Down syndrome neurons,” says Bhattacharyya. “This has been suggested before from other studies, but we were pleased to find more evidence for that. We now have a system we can manipulate to study the effects of oxidative stress and possibly prevent them.”

Down syndrome includes a range of symptoms that could result from oxidative stress, Bhattacharyya says, including accelerated aging. “In  their 40s, Down syndrome individuals age very quickly. They suddenly get gray hair; their skin wrinkles, there is rapid aging in many organs, and a quick appearance of Alzheimer’s disease. Many of these processes may be due to increased oxidative stress, but it remains to be directly tested.”

Oxidative stress could be especially significant, because it appears right from the start in the stem cells. “This suggests that these cells go through their whole life with oxidative stress,” Bhattacharyya adds, “and that might contribute to the death of neurons later on, or increase susceptibility to Alzheimer’s.”

Other researchers have created neurons with Down syndrome from induced pluripotent stem cells, Bhattacharyya notes. “However, we are the first to report this synaptic deficit, and to report the effects on genes on other chromosomes in neurons. We are also the first to use stem cells from the same person that either had or lacked the extra chromosome. This allowed us to look at the difference just caused by extra chromosome, not due to the genetic difference among people.”

The research, published the week of May 27 in the Proceedings of the National Academy of Sciences, was a basic exploration of the roots of Down syndrome. Bhattacharyya says that while she did not intend to explore treatments in the short term, “we could potentially use these cells to test or intelligently design drugs to target symptoms of Down syndrome.”

What the smallest infectious agents reveal about evolution

on-the-origin-of-species:

Impressive proof of evolution and a summary of what evolution is, whether in the short or long term. A great read.