Lifeboat Foundation

Systemic gamma-aminobutyric acid (GABA) therapy prevents or ameliorates type 1 diabetes (T1D), by suppressing autoimmune responses and stimulating pancreatic beta cells. In beta cells, it increases insulin secretion, prevents apoptosis, and induces regeneration. It is unclear how GABA mediates these effects. We hypothesized that Klotho is involved. It is a multi-functional protein expressed in the kidneys, brain, pancreatic beta cells, other tissues, and is cell-bound or soluble. Klotho knockout mice display accelerated aging, and in humans Klotho circulating levels decline with age, renal disease and diabetes. Here, we report that GABA markedly increased circulating levels of Klotho in streptozotocin (STZ)-induced diabetes. GABA also increased Klotho in the islet of Langerhans of normal mice, as well as the islets and kidneys of STZ-treated mice. In vitro, GABA stimulated production and secretion of Klotho by human islet cells. Knockdown (KD) of Klotho with siRNA in INS-1E insulinoma cells abrogated the protective effects of GABA against STZ toxicity. Following KD, soluble Klotho reversed the effects of Klotho deficiency. In human islet cells soluble Klotho protected against cell death, and stimulated proliferation and insulin secretion. NF-κB activation triggers beta-cell apoptosis, and both GABA and Klotho suppress this pathway. We found Klotho KD augmented NF-κB p65 expression, and abrogated the ability of GABA to block NF-κB activation. This is the first report that GABAergic stimulation increases Klotho expression. Klotho protected and stimulated beta cells and lack of Klotho (KD) was reversed by soluble Klotho. These findings have important implications for the treatment of T1D.

Circa 2017

Hunting for meat was a critical step in all animal and human evolution. A key brain-trophic element in meat is vitamin B₃ / nicotinamide. The supply of meat and nicotinamide steadily increased from the Cambrian origin of animal predators ratcheting ever larger brains. This culminated in the 3-million-year evolution of Homo sapiens and our overall demographic success. We view human evolution, recent history, and agricultural and demographic transitions in the light of meat and nicotinamide intake. A biochemical and immunological switch is highlighted that affects fertility in the ‘de novo’ tryptophan-to-kynurenine-nicotinamide ‘immune tolerance’ pathway. Longevity relates to nicotinamide adenine dinucleotide consumer pathways. High meat intake correlates with moderate fertility, high intelligence, good health, and longevity with consequent population stability, whereas low meat/high cereal intake (short of starvation) correlates with high fertility, disease, and population booms and busts. Too high a meat intake and fertility falls below replacement levels. Reducing variances in meat consumption might help stabilise population growth and improve human capital.

Keywords: Meat, nicotinamide, evolution, NAD(H), vitamin B₃, Malthus, fertility, immunological tolerance, longevity.

Continue reading “Meat and Nicotinamide: A Causal Role in Human Evolution, History, and Demographics” »

The team compared germ-free (sterile) mice and mice with normal microbes. They used a laboratory technique called mass spectrometry to characterize the non-living molecules in every mouse organ. They identified as many molecules as possible by comparing them to reference structures in the GNPS database, a crowdsourced mass spectrometry repository developed by Dorrestein and collaborators. They also determined which living microbes co-locate with these molecules by sequencing a specific genetic region that acts as a barcode for bacterial types.

In total, they analyzed 768 samples from 96 sites of 29 different organs from four germ-free mice and four mice with normal microbes. The result was a map of all of the molecules found throughout the body of a normal mouse with microbes, and a map of molecules throughout a mouse without microbes.

A comparison of the maps revealed that as much as 70 percent of a mouse’s gut chemistry is determined by its gut microbiome. Even in distant organs, such as the uterus or the brain, approximately 20 percent of molecules were different in the mice with gut microbes.

Drug overdoses can be life threatening, but for two women who accidentally took massive hits of LSD the experience was life changing — and in a good way.

A 46-year-old woman snorted a staggering 550 times the normal recreational dose of LSD and not only survived, but found that the foot pain she had suffered from since her 20s was dramatically reduced.

Separately, a 15-year-old girl with bipolar disorder overdosed on 10 times the normal dose of the drug, which she said resulted in a massive improvement in her mental health.

Scientists say current system for labelling children with difficulties is ‘too simple’.

Scientists found parasitic worms in the brains of lizard embryos. How did they get there?

Researchers in the UK claim to have developed a microfluidic chip that can rapidly tell whether someone has suffered a traumatic brain injury from a finger-prick blood sample. The optofluidic device detects a biomarker linked to brain injury, based on the way that it scatters light (Nat. Biomed. Eng. 10.1038/s41551-019‑0510-4).

An optofluidic device uses Raman spectroscopy to detect a biomarker in blood associated with traumatic brain injury.

One of the most remarkable characteristics of the vertebrate eye is its retina. Surprisingly, the sensitive portions of the photoreceptor cells are found on the hind side of the retina, meaning that light needs to travel through living neural tissue before it can be detected. While the origin of the high optical quality of the retina remain largely uninvestigated, it has long been proposed that a peculiar DNA organization would serve to improve vision in nocturnal mammals. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics in Dresden now showed that the optical quality of the mouse retina increases in the first month after birth that imparts improved visual sensitivity under low light conditions. This improvement is caused by a compact organization of the genetic material in the cell nucleus of rod photoreceptor cells that responsible for dim light vision.

Our retina is an amazing feature of the eye of vertebrates. This light-sensitive layer of tissue is lining the back of the eye-ball and acts as a screen for images projected by the lens. The retina has a thickness of 130 to 500 micrometer and is composed of five layers of dense neural tissue. Since the sensitive portions of the photoreceptor cells are found on the hind side of the retina, light needs to travel through this dense neural tissue to reach the photoreceptors. Researchers suggested that a certain compact arrangement of DNA in the cell nucleus of the rod photoreceptors could improve night vision in nocturnal animals but it remained unclear if and how night vision would benefit from this organization of genetic material.

Scientists around the research group leader Moritz Kreysing at the Max Planck Institute of Molecular Cell Biology and Genetics together with colleagues from the TU Dresden and the Biozentrum at the Ludwig Maximilians Universität in Munich wanted to find out, if and why cells of retinal neural cells are optically special and what the implications for the transparency of the retina are. Transparency in this context means that each rod cell scatters less light, which causes it to be more transparent.

WASHINGTON: Scientists have found that people who have a variant of a longevity gene have improved brain skills such as thinking, learning and memory. Researchers found that increasing levels of the gene, called KLOTHO, in mice made them smarter, possibly by increasing the strength of connections between nerve cells in the brain.

“This could be a major step toward helping millions around the world who are suffering from Alzheimer’s disease and other dementias,” said Dena Dubal, an assistant professor of neurology, the David A Coulter Endowed Chair in Aging and Neurodegeneration at the University of California San Francisco (UCSF) and the lead author of the study published in Cell Reports. “If we could boost the brain’s ability to function, we may be able to counter dementias,” Dubal said.

People who have one copy of a variant, or form, of the KLOTHO gene, called KL-VS, tend to live longer and have lower chances of suffering a stroke whereas people who have two copies may live shorter lives and have a higher risk of stroke. In the study, researchers found that people who had one copy of the KL-VS variant performed better on a battery of cognitive tests than subjects who did not have it, regardless of age, sex or the presence of the apolipoprotein 4 gene, the main genetic risk factor for Alzheimer’s disease.