X-chromosome inactivation (XCI) is essential for extraembryonic tissue growth and embryo development in mice. However, species-specific differences in its timing and regulation have left its role in human development unclear. Here, we show that the in vitro differentiation of naive human pluripotent stem cells to trophoblast stem cells and extraembryonic mesoderm cells is accompanied by XCI. The inactive X chromosome displays an atypical chromatin state, lacking DNA methylation and canonical heterochromatin marks. We demonstrate that extraembryonic differentiation and XCI are temporally linked. Using loss of function approaches, we found that XIST is required for XCI establishment in humans. Furthermore, we show that XCI is needed for the survival of human female extraembryonic cells. Together, these findings link XCI to the formation of human extraembryonic lineages, with important implications for human reproductive biology. X-chromosome inactivation (XCI) silences one of the two X chromosomes in females, but its role in human development is unclear. Here, the authors show that human extraembryonic differentiation triggers XIST-dependent XCI, important for cell survival.
Highly compliant deformable soft actuators enable the engineering of adaptive life-like systems. Biohybrid living materials expand possibilities for autonomous, self-powered, environmentally responsive systems with easy biological integration. Here, we present a light-driven living soft actuator that integrates the photosynthetic microalga Chlamydomonas reinhardtii with a pH-responsive poly(3-(acrylamido)phenylboronic acid-acrylamide)/polyacrylamide bilayer hydrogel. When exposed to light, through photosynthesis and N-assimilation, the microalgae locally ionize the polymer network, causing the bilayer actuator to bend. In darkness, through respiration, the microalgae locally release CO2 that protonates the polymer chains, reversing the deformation. This algae actuator enables finely controlled and reversible motions, with a large bending amplitude achieved within 18 hours and an initial response time of 10-20 s, which is maintained over 10 cycles of continuous operation. We demonstrate light-controlled grippers, highlighting the potential of algae-powered actuation for sustainable and autonomous soft devices. Deformable actuators can be used for adaptive life-like systems, and biohybrid materials can expand the possibilities for responsive materials. Here the authors integrate microalgae into a pH-responsive hydrogel to achieve a biohybrid photoresponsive actuator.
Multi-Tb/s optical interconnects for artificial intelligence data centers necessitate high-speed, energy-efficient, and compact transceivers. However, conventional silicon Mach-Zehnder modulators are fundamentally limited by low modulation efficiency and large physical dimensions that typically extend several millimeters, requiring high-swing drivers and power-intensive digital signal processing to achieve data rates exceeding 100 Gb/s per lane. Here we show a silicon photonic crystal waveguide slow-light modulator that overcomes the bandwidth-efficiency trade-off via a built-in electro-optic equalizer. By monolithically integrating optical delay lines and crossings within segmented slow-light phase shifters, we synthesized an on-chip feedforward response that extends the 3-dB bandwidth. The fabricated modulator with a small device length of 320 µm demonstrated 140-Gb/s on-off keying operation with an energy consumption of 26 fJ/bit using drive voltages compatible with fin field-effect transistor-based complementary metal-oxide-semiconductor technology. Furthermore, four-level pulse amplitude modulation achieved 180 Gb/s without digital signal processing and 200 Gb/s with a low-complexity 11-tap digital equalizer. By reducing reliance on power-dissipating electronics, this strategy provides a potential route toward future dense multi-Tb/s co-packaged optics for energy-constrained switching systems. Silicon photonic modulators are central to future high-capacity optical interconnects but face a trade-off between efficiency and bandwidth. This work addresses that challenge using a slow-light modulator with an integrated EO equalizer, enabling 200 Gb/s operation.
Blood phosphorylated tau 217 (p-tau217) accurately detects Alzheimer’s disease (AD) pathology but is also elevated in amyotrophic lateral sclerosis (ALS), likely reflecting peripheral (big) tau released from muscle. Assays selectively measuring brain-derived (BD-) tau and BD-p-tau217 are therefore needed. We analysed serum BD-tau and p-tau217 in ALS (n = 139), AD (n = 101) and controls (n = 75) using direct immunoassays and after BD-Tau immunoprecipitation (BD-Tau-IP), and tau species in brain (n = 16), spinal cord (n = 11) and muscle (n = 10) by targeted mass spectrometry. With the direct immunoassays, BD-tau and p-tau217 were increased in AD and ALS versus controls. After BD-Tau-IP, BD-tau and BD-p-tau217 were elevated in AD only, improving diagnostic accuracy. Mass spectrometry revealed a central-to-peripheral shift from BD-tau to big tau predominance, with exclusively big p-tau217 detected in muscle. Selective detection of BD-tau species improves the specificity of blood AD biomarkers by reducing peripheral tau confounding. Blood p-tau217 is a leading Alzheimer’s test but is also raised in ALS. Here, the authors show that muscle makes its own form of tau which leaks into the blood, and that detecting brain-derived p-tau217 improves the test’s accuracy.
