Lifeboat Foundation

Summary: Scientists are using epigenetic clocks to reveal our biological age, a true marker of health.

A new study delves into the immune system’s role in understanding and improving the accuracy of these clocks. Their innovative approach sheds light on the relationship between immune cell composition and biological age, with a focus on the balance between naïve and memory immune cells.

This research has significant implications for aging insights, health interventions, and targeted cancer treatments.

In this study, we conducted behavioral experiments and measured survival rates in local caves to minimize the impacts of factors other than light. Although energy-costly eyes were highly reduced or lost in cave-dwelling Leptonetela spiders, which spend their entire life cycles in the complete absence of light, our results demonstrated that they could detect light, and light cues may be used to avoid the perilously dry environment outside the cave. The annotation of core PPGs based on transcriptomic data suggests that cave-dwelling Leptonetela spiders have retained a nearly complete set of PPGs as in the entrance spiders. The molecular evolutionary analysis showed strong purifying selection on PPGs of cave-dwelling Leptonetela spiders. Therefore, our study provides evidence supporting the hypothesis that the phototransduction system of cave-dwelling eyeless Leptonetela spiders may have been under purifying selection rather than being a phylogenetic relic. Our results thus refute the neutral hypothesis.

Leptonetela spiders are small cryptozoic spiders that build sheet webs for capturing prey in twilight or lightless environment, such as leaf litter, rotting logs, rock crevices, and caves (31). Light is suggested to be the primary selective force driving the evolution of eyes of cave animals, thus, eyes are often reduced or lost as cave preadaptation in many litter-dwelling arthropods (36–38). Leptonetela spiders have lost anterior median eyes that are generally involved in identifying and stalking prey in spiders, likely due to their twilight or lightless habitats. In addition, cave-dwelling Leptonetela spiders living in lightless deep caves exhibit various degrees of eye reduction (highly reduced or eyeless) compared to their entrance spider relatives that have six intact eyes. Thus, Leptonetela spiders provided an ideal system for studying the evolution of eyes and visual systems.

This study provides evidence demonstrating negative phototaxis in cave-dwelling spiders, a highly diverse group that plays a critical role in cave ecosystems as top predators (23). Negative phototaxis has frequently been found in other subterranean animals. For example, the cave-dwelling carrion beetle Ptomaphagus hirtus that has highly reduced eyes nonetheless displays strongly negative phototaxis and maintains a reduced but functional phototransduction system, as shown by transcriptomic data (13). However, Langille et al. (14) reported that five of six subterranean water beetles completely lacked phototactic responses, and the authors proposed negative phototaxis as a preadaptation to living in permanent darkness for ancestral cave-dwelling animals. We speculate that drought resistance may play an important role in the retention of PPGs in Leptonetela spiders.

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Scientific knowledge can progress rapidly, yet its social, economic, and political impacts often unfold at a painstakingly slow pace. The medicine of the 21st century draws upon genetic and embryological breakthroughs of the 19th century. Our current technology is firmly grounded in quantum physics, which was formulated a century ago. And the topic of the day, artificial intelligence (AI), traces its origins to the secret weapons research during World War II.

‌In 1935, the brilliant British mathematician, Alan Turing, envisioned a conceptual computer. His genius would later lead him to crack the Enigma code used by German submarines for secret communications during the war. Turing’s contributions extended beyond cryptography, as he introduced fundamental concepts of AI, including the training of artificial neural networks. Benedict Cumberbatch portrayed Turing in the 2014 film The Imitation Game, which earned a screenplay Oscar that year. All this historical context brings us to the heart of the current AI revolution.

‌AI uses neural networks, also known as artificial neural networks, which are comprised of multiple layers of artificial neurons. Each neuron receives numerous inputs from the lower layer and produces a single output to the upper layer, similar to the dendrites and axon of natural neurons. As information progresses through each layer, it gradually becomes more abstract, resembling the process that occurs in the visual cortex of our brains.

Aera Therapeutics, a startup launched by the CRISPR pioneer Feng Zhang last year to solve one of the biggest bottlenecks in genetic medicine, has laid off a quarter of its staff, the company confirmed to STAT.

The layoffs come as the biotech market remains mired in a now nearly three-year-long downturn that has left startups struggling to attract both private and public funds. Aera attributed the layoffs to those headwinds and indicated it had axed a portion of the company dedicated to developing new gene-editing enzymes.

“In 2023, Aera launched to pursue an ambitious mission to develop transformative genetic medicines by harnessing enabling delivery technologies and precision payloads,” spokesman Dan Budwick said in a statement. “Although Aera remains in a strong cash position today, given the current biotech funding environment, we have chosen to take steps to focus our strategy and investments on the development of our novel delivery platforms, thereby further extending our cash runway.”

Radon, a naturally occurring radioactive gas produced when metals like uranium or radium break down in rocks and soil, is a known cause of lung cancer. Now new research has found exposure to high levels of this indoor air pollutant is associated with an increased risk of another condition in middle age to older female participants with ischemic stroke. The study is published in the January 3, 2024, online issue of Neurology, the medical journal of the American Academy of Neurology. Ischemic stroke is caused by a blockage of blood flow to the brain and is the most common type of stroke.

The condition, called clonal hematopoiesis of indeterminate potential (CHIP), develops when some hematopoietic stem cells, the building blocks for all blood cells, undergo genetic mutations as a person ages. Cells with such mutations replicate more quickly than cells without them. Previous research has shown people with CHIP may have a higher risk of blood cancers like leukemia and cardiovascular disease including stroke.

Continue reading “Is Radon linked to health condition other than lung cancer?” »

Over the past decades, scientists have made substantial progress unveiling the underlying mechanisms behind many psychiatric disorders. Every year, new genetic mutations or protein dysregulations are identified as potential culprits for the symptoms and sometimes even the root causes of complex neurological diseases, including autism spectrum disorder (ASD), schizophrenia, and Alzheimer’s.

Despite these efforts, the precise roles of several proteins involved in brain function remain obscure. Such is the case for indoleamine 2,3-dioxygenase 2 (IDO2), an enzyme expressed in the brain and metabolized by the tryptophan–kynurenine pathway (TKP).

Changes in the metabolites of this pathway have already been linked to many psychiatric disorders, and genetically modified mice have been invaluable tools in such studies. However, the detailed functions of IDO2 in the brain are not known.

In a recent study published in Molecular Psychiatry, researchers explored the effects of a small humanin-like peptide 2 (SHLP2) variant on mitochondrial function.

Mitochondria are implicated in Parkinson’s disease (PD) pathogenesis. Mitochondrial-derived peptides (MDPs) are microproteins encoded from small open reading frames (sORFs) in the mitochondrial DNA (mtDNA). SHLP2 is an MDP with an essential role in multiple cellular processes, and it improves mitochondrial metabolism by increasing biogenesis and respiration and reducing oxidation.

Recent studies link mitochondrial single nucleotide polymorphisms (mtSNPs) within coding regions of MDPs to age-related deficits. For instance, m.2706 A G, an mtSNP in humanin, predicts reduced circulating levels of humanin and worse cognitive decline. Moreover, another mtSNP, m.2158 T C, is associated with reduced PD risk, albeit the underlying mechanisms are unknown.

Animals exhibit a diverse behavioral repertoire when exploring new environments and can learn which actions or action sequences produce positive outcomes. Dopamine release upon encountering reward is critical for reinforcing reward-producing actions^{1 – 3}. However, it has been challenging to understand how credit is assigned to the exact action that produced dopamine release during continuous behavior. We investigated this problem with a novel self-stimulation paradigm in which specific spontaneous movements triggered optogenetic stimulation of dopaminergic neurons. Dopamine self-stimulation rapidly and dynamically changes the structure of the entire behavioral repertoire. Initial stimulations reinforced not only the stimulation-producing target action, but also actions similar to target and actions that occurred a few seconds before stimulation. Repeated pairings led to gradual refinement of the behavioral repertoire to home in on the target. Reinforcement of action sequences revealed further temporal dependencies of refinement. Action pairs spontaneously separated by long time intervals promoted a stepwise credit assignment, with early refinement of actions most proximal to stimulation and subsequent refinement of more distal actions. Thus, a retrospective reinforcement mechanism promotes not only reinforcement, but gradual refinement of the entire behavioral repertoire to assign credit to specific actions and action sequences that lead to dopamine release.

F.C. is the Director of Open Ephys Production Site.