Tag: mice

Bioethics Blogs

Protein Links Gut Microbes, Biological Clocks, and Weight Gain

Caption: Lipids (red) inside mouse intestinal cells with and without NFIL3.
Credit: Lora V. Hooper, University of Texas Southwestern Medical Center, Dallas

The American epidemic of obesity is a major public health concern, and keeping off the extra pounds is a concern for many of us. Yet it can also be a real challenge for people who may eat normally but get their days and nights mixed up, including night-shift workers and those who regularly travel overseas. Why is that?

The most obvious reason is the odd hours throw a person’s 24-hour biological clock—and metabolism—out of sync. But an NIH-funded team of researchers has new evidence in mice to suggest the answer could go deeper to include the trillions of microbes that live in our guts—and, more specifically, the way they “talk” to intestinal cells. Their studies suggest that what gut microbes “say” influences the activity of a key clock-driven protein called NFIL3, which can set intestinal cells up to absorb and store more fat from the diet while operating at hours that might run counter to our fixed biological clocks.

NFIL3 is a transcription factor, a protein that switches certain genes on and off. Earlier studies had focused on its role in immune cells, but a team led by Lora Hooper at the University of Texas Southwestern Medical Center, Dallas, discovered that NFIL3 is also found in cells in the inner lining, or epithelium, of the mouse small intestine.

Intriguingly, as reported recently in the journal Science [1], they noticed that NFIL3 levels were much lower in the intestines of “germ-free” mice that don’t have any gut microbes.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

3D artificial ovary constructed with excellent results. New hope for women infertility

A team of researchers from the McCormick School of Engineering at Northwestern University in the United States has reported that it has managed to construct the structure of an artificial ovary 3D  (see HERE) a hydrogel that, once transplanted in an animal, can interact with its tissues and create a functioning ovary. This artificial scaffold was implanted in sterilized female mice, with cell division to ovulation taking place in two months. After mating, these females became pregnant and gave birth to healthy mice that survived, after being nursed by their mothers. This is undoubtedly a great technological breakthrough with visions of being used in humans to resolve infertility issues (see HERE).

La entrada 3D artificial ovary constructed with excellent results. New hope for women infertility aparece primero en Bioethics Observatory.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Charlie Gard Post-Mortem: Could He Have Been Saved?

Charlie Gard would have turned one year old tomorrow.

Two days before the British infant died of a mitochondrial disease on July 28, a short article in MIT Technology Review teased that Shoukhrat Mtalipov and his team at Oregon Health & Science University and colleagues had used CRISPR-Cas9 to replace a mutation in human embryos, a titillating heads-up that didn’t actually name the gene or disease.

Yesterday Nature published the details of what the researchers call gene correction, not editing, because it uses natural DNA repair. I covered the news conference, with a bit of perspective, for Genetic Literacy Project.

Might gene editing enable Charlie’s parents, who might themselves develop mild symptoms as they age, to have another child free of the family’s disease? Could anything have saved the baby?

A TRAGIC CASE

The court hearing testimony on the case between Great Ormond Street Hospital (GOSH) and the family, published April 11, chronicles the sad story. The hospital had requested discontinuing life support based on the lack of tested treatment.

Charlie was born August 4, 2016, at full term and of a good weight, but by a few weeks of age, his parents noticed that he could no longer lift his head nor support any part of his body. By the October 2 pediatrician visit, Charlie hadn’t gained any weight, despite frequent breastfeeding. After an MRI and EEG, Charlie had a nasogastric tube inserted to introduce high-caloric nutrition.

By October 11, the baby was lethargic, his breathing shallow. So his parents, Connie Yates and Chris Gard, took him to GOSH.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Charlie Gard Post-Mortem: Could He Have Been Saved?

Charlie Gard would have turned one year old tomorrow.

Two days before the British infant died of a mitochondrial disease on July 28, a short article in MIT Technology Review teased that Shoukhrat Mtalipov and his team at Oregon Health & Science University and colleagues had used CRISPR-Cas9 to replace a mutation in human embryos, a titillating heads-up that didn’t actually name the gene or disease.

Yesterday Nature published the details of what the researchers call gene correction, not editing, because it uses natural DNA repair. I covered the news conference, with a bit of perspective, for Genetic Literacy Project.

Might gene editing enable Charlie’s parents, who might themselves develop mild symptoms as they age, to have another child free of the family’s disease? Could anything have saved the baby?

A TRAGIC CASE

The court hearing testimony on the case between Great Ormond Street Hospital (GOSH) and the family, published April 11, chronicles the sad story. The hospital had requested discontinuing life support based on the lack of tested treatment.

Charlie was born August 4, 2016, at full term and of a good weight, but by a few weeks of age, his parents noticed that he could no longer lift his head nor support any part of his body. By the October 2 pediatrician visit, Charlie hadn’t gained any weight, despite frequent breastfeeding. After an MRI and EEG, Charlie had a nasogastric tube inserted to introduce high-caloric nutrition.

By October 11, the baby was lethargic, his breathing shallow. So his parents, Connie Yates and Chris Gard, took him to GOSH.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Snapshots of Life: Muscling in on Development

Credit: Gabrielle Kardon, University of Utah, Salt Lake City

Twice a week, I do an hour of weight training to maintain muscle strength and tone. Millions of Americans do the same, and there’s always a lot of attention paid to those upper arm muscles—the biceps and triceps. Less appreciated is another arm muscle that pumps right along during workouts: the brachialis. This muscle—located under the biceps—helps your elbow flex when you are doing all kinds of things, whether curling a 50-pound barbell or just grabbing a bag of groceries or your luggage out of the car.

Now, scientific studies of the triceps and brachialis are providing important clues about how the body’s 40 different types of limb muscles assume their distinct identities during development [1]. In these images from the NIH-supported lab of Gabrielle Kardon at the University of Utah, Salt Lake City, you see the developing forelimb of a healthy mouse strain (top) compared to that of a mutant mouse strain with a stiff, abnormal gait (bottom).

In each strain, you see the lateral triceps and brachialis muscles (purple), other types of muscle (red) and tendons (green). However, in the healthy mouse, the lateral triceps and brachialis muscles are distinct, which gives the forelimb its flexibility; while in the mutant mouse, the two muscles are fused and indistinct, limiting the forelimb’s function.

The mice with the abnormal lateral triceps and brachialis have a mutation in a gene called Tbx3, which codes for a transcription factor that switches other genes off and on. If you follow this blog, you know that a lot of exciting research is currently focused on transcription factors, including how precise combinations of transcription factors can turn skin cells into blood stem cells or be used to make neurons.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Charlie Gard, the sick baby hospital doctors want to disconnect. Our medical and ethical assessement

He and his parents await the Judge’s decision regarding the possibility of withdrawing or not the life support who keep him alive and the possibility of receiving an experimental treatment in the United States

Medical aspects

Charlie was born on 4 August 2016. In October the same year, he was admitted to Great Osmond Street Hospital (GOSH-NHS) in London, and diagnosed with a disease that affects mitochondrial function, called mitochondrial DNA depletion syndrome (MDDS). This means that he cannot obtain sufficient energy for his muscles, kidneys, brain and other organs, which causes progressive muscle weakness and brain damage.

Although there seemed to be no specific treatment for the mitochondrial abnormality at that time, in January 2017, his mother became aware of an experimental treatment using nucleosides that was being evaluated in the United States in patients with a disease similar to Charlie’s. Consequently, his parents assessed the possibility of taking him to the US for treatment because, according to them, it might improve their son’s health by at least 10%.

At the same time, British newspaper “The Guardian” announced that the US Hospital that had the medication offered to ship it so that Charlie could be treated immediately, but GOSH (NHS hospital) disagreed, proposing instead to withdraw the child’s respiratory support.

In effect, New York-Presbyterian Hospital and Irving Medical Center, also in New York, published a statement saying that they were willing to admit and clinically evaluate Charlie, as they had FDA approval for the use of an experimental treatment using nucleosides.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics Blogs

Creative Minds: Reprogramming the Brain

Caption: Neuronal circuits in the mouse retina. Cone photoreceptors (red) enable color vision; bipolar neurons (magenta) relay information further along the circuit; and a subtype of bipolar neuron (green) helps process signals sensed by other photoreceptors in dim light.
Credit: Brian Liu and Melanie Samuel, Baylor College of Medicine, Houston.

When most people think of reprogramming something, they probably think of writing code for a computer or typing commands into their smartphone. Melanie Samuel thinks of brain circuits, the networks of interconnected neurons that allow different parts of the brain to work together in processing information.

Samuel, a researcher at Baylor College of Medicine, Houston, wants to learn to reprogram the connections, or synapses, of brain circuits that function less well in aging and disease and limit our memory and ability to learn. She has received a 2016 NIH Director’s New Innovator Award to decipher the molecular cues that encourage the repair of damaged synapses or enable neurons to form new connections with other neurons. Because extensive synapse loss is central to most degenerative brain diseases, Samuel’s reprogramming efforts could help point the way to preventing or correcting wiring defects before they advance to serious and potentially irreversible cognitive problems.

Melanie Samuel

Melanie Samuel

The human brain is wired with a vast number of circuits. They travel winding, contorted paths through the densely packed neurons in the human brain, making them extremely difficult to study. Samuel will start in less expansive and daunting neural terrain. She has chosen to focus first on synapses in the mouse retina, the complex neural tissue that lines the back of the eye.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

Memory-Enhancing Drug Reverses Effects of Traumatic Brain Injury In Mice

Whether caused by a car accident or repeated blows to your cranium from high-contact sports, traumatic brain injury can be permanent. There are no drugs to reverse the cognitive decline and memory loss, and any surgical interventions must be carried out within hours to be effective, according to the current medical wisdom. But a compound previously used to enhance memory in mice may offer hope

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.

Bioethics News

The amazing finding of senescent cells in embryos. Until now, these cells had been found only in aging tissue

The discovery raises the possibility that the start and end of life are intimately connected

The process by which cells cease multiplying is known as senescence. In 1961, biologists Hayflick and Moorehead cryoconserved human fetal cells and found that these divide around 50 times and then simply stop doing so, as occurs in the human body (see recent article, AGING CELLS ARE KEY TO FINDING FOUNTAIN OF YOUTH)

In fact, senescent cells are involved in many of the signs of aging: wrinkled skin, cataracts, and arthritic joints, which are produced by the effect of an increase in these cells. On the contrary, it has been found that by decreasing senescent cells in mice, signs of rejuvenation can be detected in these animals.

Considering that in all research, senescent cells have been found only in old or damaged tissues, the last place one would expect to find them would be at the very beginning of life, in the embryo. Now, however, three scientific teams have reported that they have observed the same phenomenon at this point.

Senescent cells in embryos

For the first time, senescent cells have been found in embryos, and scientists have presented proof that senescence is crucial for their proper development.

This discovery raises the possibility that the start and end of life are intimately connected. In order for life to have a good start, senescent cells are needed, i.e. youth needs a little bit of old age.

Scott Lowe, an expert in senescence at Memorial Sloan-Kettering Cancer Center, who did not participate in the research, has lauded the studies, which point to the unexpected role of old age, and predicted that it would provoke a spirited debate between developmental biologists, who study how embryos are formed.

The views, opinions and positions expressed by these authors and blogs are theirs and do not necessarily represent that of the Bioethics Research Library and Kennedy Institute of Ethics or Georgetown University.