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Category: biotech/medical – Page 118

A bioelectrical phase transition patterns the first vertebrate heartbeats

A regular heartbeat is essential to vertebrate life. In the mature heart, this function is driven by an anatomically localized pacemaker. By contrast, pacemaking capability is broadly distributed in the early embryonic heart1–3, raising the question of how tissue-scale activity is first established and then maintained during embryonic development. The initial transition of the heart from silent to beating has never been characterized at the timescale of individual electrical events, and the structure in space and time of the early heartbeats remains poorly understood. Using all-optical electrophysiology, we captured the very first heartbeat of a zebrafish and analysed the development of cardiac excitability and conduction around this singular event. The first few beats appeared suddenly, had irregular interbeat intervals, propagated coherently across the primordial heart and emanated from loci that varied between animals and over time. The bioelectrical dynamics were well described by a noisy saddle-node on invariant circle bifurcation with action potential upstroke driven by CaV1.2. Our work shows how gradual and largely asynchronous development of single-cell bioelectrical properties produces a stereotyped and robust tissue-scale transition from quiescence to coordinated beating.

© 2023. The Author(s), under exclusive licence to Springer Nature Limited.

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Elon Musk on AGI Timeline, US vs China, Job Markets, Clean Energy & Humanoid Robots

Questions to inspire discussion.

🤖 Q: How quickly will AI and robotics replace human jobs? A: AI and robotics will do half or more of all jobs within the next 3–7 years, with white-collar work being replaced first, followed by blue-collar labor through humanoid robots.

🏢 Q: What competitive advantage will AI-native companies have? A: Companies that are entirely AI-powered will demolish competitors, similar to how a single manually calculated cell in a spreadsheet makes it unable to compete with entirely computer-based spreadsheets.

💼 Q: What forces companies to adopt more AI? A: Companies using more AI must outcompete those using less, creating a forcing function for increased AI adoption, as inertia currently keeps humans doing AI-capable tasks.

📊 Q: How much of enterprise software development can AI handle autonomously? A: Blitzy, an AI platform using thousands of specialized agents, autonomously handles 80%+ of enterprise software development, increasing engineering velocity 5x when paired with human developers.

Energy and Infrastructure.

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Viral evasion of cGAS-STING pathway: opportunities for intervention

The cyclic GMP-AMP (cGAMP) synthase (cGAS) and stimulator of interferon genes (STING) pathway, a crucial component of host innate immunity, detects aberrant DNA during viral infection. It is well established that cGAS-STING signaling activation during viral infections is often insufficient for complete viral clearance, indicating that numerous viruses have evolved countermeasures against this major pathway. However, the precise mechanisms by which viruses antagonize the cGAS-STING pathway to ensure intracellular survival remain incompletely understood. This review synthesizes recent progress in elucidating how diverse RNA and DNA viruses disrupt various stages of cGAS-STING pathway activation. These mechanistic insights into viral evasion have significant implications for the development of targeted therapeutic interventions.

Abstract: Can we help fat cells get in shape in diabetes?

Here, James C. Lo & team identify FAM20C as a key mediator of obesity-induced adipocyte dysfunction and inflammation, suggesting its inhibition as a potential therapy for Type2 Diabetes:

The figure shows visceral white adipose tissue in mice with adipocyte-specific deletion of Fam20c shifts shows lower macrophage area compared with controls.

1Division of Cardiology, Department of Medicine, Weill Center for Metabolic Health, Cardiovascular Research Institute, and.

2Department of Medicine, Weill Cornell Medicine, New York, New York, USA.

3Helmholtz Institute for Metabolic, Obesity, and Vascular Research, Helmholtz Center Munich, University of Leipzig and University Hospital Leipzig, Leipzig, Germany.

This CRISPR breakthrough turns genes on without cutting DNA

A new CRISPR breakthrough shows scientists can turn genes back on without cutting DNA, by removing chemical tags that act like molecular anchors. The work confirms these tags actively silence genes, settling a long-running scientific debate. This gentler form of gene editing could offer a safer way to treat Sickle Cell disease by reactivating a fetal blood gene. Researchers say it opens the door to powerful therapies with fewer unintended side effects.

Astrocyte CCN1 stabilizes neural circuits in the adult brain

In early life, astrocytes help to mold neural pathways in response to the environment. In adulthood, however, those cells curb plasticity by secreting a protein that stabilizes circuits, according to a mouse study published last month in Nature.

“It’s a new and unique take on the field,” says Ciaran Murphy-Royal, assistant professor of neuroscience at Montreal University, who was not involved in the study. Most research focuses on how glial cells drive plasticity but “not how they apply the brakes,” he says.

Astrocytes promote synaptic remodeling during the development of sensory circuits by secreting factors and exerting physical control—in humans, a single astrocyte can clamp onto 2 million synapses, previous studies suggest. But the glial cells are also responsible for shutting down critical periods for vision and motor circuits in mice and fruit flies, respectively.

It has been unclear whether this loss of plasticity can be reversed. Some evidence hints that modifying the neuronal environment—through matrix degradation or transplantation of young neurons—can rekindle flexibility in adult brains.

The new findings confirm that in adulthood, plasticity is only dormant, rather than lost entirely, says Nicola Allen, professor of molecular neurobiology at the Salk Institute for Biological Studies and an investigator on the new paper. “Neurons don’t lose an intrinsic ability to remodel, but that process is controlled by secreted factors in the environment,” she says.

Specifically, astrocytes orchestrate that dormancy by releasing CCN1, a protein that stabilizes circuits by prompting the maturation of inhibitory neurons and glial cells, Allen’s team found. The findings suggest that astrocytes have an active role in stabilizing adult brain circuits.

The loss of plasticity in adulthood is often seen as a “sad feature of getting older,” says Laura Sancho Fernandez, project manager in Guoping Feng’s lab at the Massachusetts Institute of Technology, who worked on the study as a postdoctoral researcher in Allen’s lab. “But it’s really important for maintaining stable representations and circuits in the brain.”

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