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Biotech startup Lucy Therapeutics is developing mitochondrial-based small molecule therapies for neurological diseases and recently revealed the first two drugs to emerge from its lead programme targeting Parkinson’s. The company, which takes its name from the 3.2-million-year-old fossil of an ancestor of humankind, presented “promising preclinical data” at the Michael J Fox Foundation’s Parkinson’s Disease Therapeutics Conference in October.

The data shown by Lucy Therapeutics demonstrated that its compounds were able to reverse mitochondrial dysfunctions linked to Parkinson’s. In cellular models of the disease, the drugs boosted levels of cellular energy molecule ATP, prevented the death of neurons, and reduced levels of other hallmarks of Parkinson’s, including a-synuclein.

Longevity. Technology: Mitochondria are widely known as the ‘power generators’ within our cells, and their dysfunction has been linked to a range of age-related diseases. But the role of mitochondria extends beyond cellular energy as they also dictate many of a cell’s key functions. Lucy Therapeutics was founded on the hypothesis that diseases with rate-limiting steps involving mitochondrial dysfunction can potentially be treated by modulating key mitochondrial protein targets. To find out more, we caught up with the company’s founder and CEO, Dr Amy Ripka.

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Biological supramolecular assemblies, such as phospholipid bilayer membranes, have been used to demonstrate signal processing via short-term synaptic plasticity (STP) in the form of paired pulse facilitation and depression, emulating the brain’s efficiency and flexible cognitive capabilities. However, STP memory in lipid bilayers is volatile and cannot be stored or accessed over relevant periods of time, a key requirement for learning. Using droplet interface bilayers (DIBs) composed of lipids, water and hexadecane, and an electrical stimulation training protocol featuring repetitive sinusoidal voltage cycling, we show that DIBs displaying memcapacitive properties can also exhibit persistent synaptic plasticity in the form of long-term potentiation (LTP) associated with capacitive energy storage in the phospholipid bilayer. The time scales for the physical changes associated with the LTP range between minutes and hours, and are substantially longer than previous STP studies, where stored energy dissipated after only a few seconds. STP behavior is the result of reversible changes in bilayer area and thickness. On the other hand, LTP is the result of additional molecular and structural changes to the zwitterionic lipid headgroups and the dielectric properties of the lipid bilayer that result from the buildup of an increasingly asymmetric charge distribution at the bilayer interfaces.

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Ablation of primary cilia in the striatum did not affect the object recognition memory, as evidenced by the more time mice spent with the novel object than the old object (Fig. 4e, f). Similarly, in the novel location recognition assay, IFT88-KO spent more time with the novel location than the old location (Fig. 4g, h), indicating a normal spatial memory. In addition, the contextual memory, measured using the fear conditioning test, was intact in the IFT88-KO mice, as revealed by the similar freezing time on the test day compared with the control mice (Fig. 4i).

The expression of the immediate-early gene cFos was used as a molecular marker of neural activity. We examined cFos immunoreactivity (number of cFos-positive cells) in structures that are parts of striatal circuits and those known to project to or receive projections from the striatum (Fig. 5a, b). First, the rostral dorsal striatum, but not the caudal striatum of IFT88-KO mice, exhibited a significant decrease of cFos immunoreactivity (Fig. 5c, d). Within the basal ganglia circuit, there was a trend for cFos immunoreactivity reductions in the output regions (SNr and the GPm), but not in the nuclei of the indirect pathway structures (lateral globus pallidus and subthalamic nucleus) (Fig. 5c, d). The main input regions to the striatum include the dopaminergic neurons of the substantia nigra pars compact (SNc) and the glutamatergic neurons of the cortices.

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Mammalian sex chromosomes are highly conserved, and sex is determined by SRY on the Y chromosome. Two exceptional rodent groups in which some species lack a Y chromosome and Sry offer insights into how novel sex genes can arise and replace Sry, leading to sex chromosome turnover. However, intensive study over three decades has failed to reveal the identity of novel sex genes in either of these lineages. We here report our discovery of a male-specific duplication of an enhancer of Sox9 in the Amami spiny rat Tokudaia osimensis, in which males and females have only a single X chromosome (XO/XO) and the Y chromosome and Sry are completely lost. We performed a comprehensive survey to detect sex-specific genomic regions in the spiny rat. Sex-related genomic differences were limited to a male-specific duplication of a 17-kb unit located 430 kb upstream of Sox9 on an autosome. Hi-C analysis using male spiny rat cells showed the duplicated region has potential chromatin interaction with Sox9. The duplicated unit harbored a 1,262-bp element homologous to mouse enhancer 14 (Enh14), a candidate Sox9 enhancer that is functionally redundant in mice. Transgenic reporter mice showed that the spiny rat Enh14 can function as an embryonic testis enhancer in mice. Embryonic gonads of XX mice in which Enh14 was replaced by the duplicated spiny rat Enh14 showed increased Sox9 expression and decreased Foxl2 expression. We propose that male-specific duplication of this Sox9 enhancer substituted for Sry function, defining a novel Y chromosome in the spiny rat.

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Accelerating particles to relativistic speeds typically requires particle accelerators that are many kilometers in length. Miniature particle accelerators a few tens of centimeters long or smaller also exist. These so-called laser-plasma accelerators are being tested in research facilities for future use in hospitals, where scientists hope the accelerators could generate x rays for cancer diagnostics and treatment. In these devices, particles are accelerated by short laser pulses, so scientists have only a few femtoseconds to track the particles’ evolving properties. Now Simon Bohlen of the German Electron Synchrotron (DESY) and colleagues experimentally demonstrate a technique to measure the energy evolution of an electron bunch inside a laser-plasma accelerator [1]. The team hopes that the technique could be used to improve laser-plasma accelerators and ready them to generate x rays for medical applications.

For their demonstration Bohlen and colleagues used a phenomenon called Thomson scattering, which is the scattering of photons by electrons. They split in two the laser beam used to accelerate the electrons, using one part for normal electron acceleration and the other part to create a Thomson laser—a beam of photons the accelerated electrons could scatter. They then overlapped the Thomson laser and the accelerated electrons such that the two interacted at 20 locations over a 400- m distance. The team measured the energy of the photons scattered during these interactions using an x-ray detector. From these measurements, the team reconstructed the energy evolution of the electrons over most of the accelerator length without destroying the electron beam.

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A textbook theory for the freezing of water also explains the growth of a new phase in a more complicated phase transition of a different material.

When water freezes, the ice forms first in “nuclei”—tiny seed crystals that can grow or shrink and survive only if they reach a minimum size—at least according to the textbook theory. Researchers have now shown that this understanding also applies to a more complicated phase transition in vanadium dioxide (VO2), a material whose electrical properties and crystal structure both change at its so-called metal-to-insulator phase transition [1]. The team measured the threshold size for the “seeds” that drive this transition and demonstrated a new technique for studying crystal structure transitions. The result suggests that the classical nucleation theory is valid for a range of materials that are important in areas such as catalysis, lasers, and alloy and ceramic manufacturing.

Place a bucket of purified water in a subfreezing-temperature environment, and tiny ice seeds will start forming. Many will quickly dissolve, but those that are larger than a certain threshold size will grow and eventually merge to make a single block of ice. This view of crystallization, associated with classical nucleation theory, has been well accepted for the water–ice transition. Junqiao Wu of the University of California, Berkeley, and his colleagues wanted to test whether the same nucleation phenomenon is at play in VO2 when it makes a transition from one crystalline structure to another.

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