How time is measured by neural stem cells during temporal neurogenesis has remained unresolved. By combining experiments and computational modeling, we define a Shh/Gli-driven three-node timer underlying the sequential generation of motor neurons (MNs) and serotonergic neurons in the brainstem. The timer is founded on temporal decline of Gli-activator and Gli-repressor activities established through down-regulation of Gli transcription. The circuitry conforms an incoherent feed-forward loop, whereby Gli proteins not only promote expression of Phox2b and thereby MN-fate but also account for a delayed activation of a self-promoting transforming growth factor-β (Tgfβ) node triggering a fate switch by repressing Phox2b. Hysteresis and spatial averaging by diffusion of Tgfβ counteract noise and increase temporal accuracy at the population level, providing a functional rationale for the intrinsically programmed activation of extrinsic switch signals in temporal patterning. Our study defines how time is reliably encoded during the sequential specification of neurons.The coastal Pacific Northwest USA hosts thousands of deep-seated landslides. Historic landslides have primarily been triggered by rainfall, but the region is also prone to large earthquakes on the 1100-km-long Cascadia Subduction Zone megathrust. Little is known about the number of landslides triggered by these earthquakes because the last magnitude 9 rupture occurred in 1700 CE. Here, we map 9938 deep-seated bedrock landslides in the Oregon Coast Range and use surface roughness dating to estimate that past earthquakes triggered fewer than half of the landslides in the past 1000 years. We find landslide frequency increases with mean annual precipitation but not with modeled peak ground acceleration or proximity to the megathrust. Our results agree with findings about other recent subduction zone earthquakes where relatively few deep-seated landslides were mapped and suggest that despite proximity to the megathrust, most deep-seated landslides in the Oregon Coast Range were triggered by rainfall.Comparative research indicates that projections from midbrain dopamine nuclei [including the ventral tegmental area (VTA)] to the ventral striatum [including the nucleus accumbens (NAcc)] critically support motivated behavior. Using diffusion-weighted imaging and probabilistic tractography in humans, we characterized the trajectory and structure of two tracts connecting the VTA and NAcc, as well as others connecting the substantia nigra and dorsal striatum. Decreased structural coherence of an inferior VTA-NAcc tract was primarily and replicably associated with increased trait impulsivity and also distinguished individuals with a stimulant use disorder from healthy controls. These findings suggest that decreased coherence of the inferior VTA-NAcc tract is associated with increased impulsivity in humans and identify a previously uncharacterized structural target for diagnosing disorders marked by impulsivity.Arctic sea ice affects climate on seasonal to decadal time scales, and models suggest that sea ice is essential for longer anomalies such as the Little Ice Age. However, empirical evidence is fragmentary. Here, we reconstruct sea ice exported from the Arctic Ocean over the past 1400 years, using a spatial network of proxy records. We find robust evidence for extreme export of sea ice commencing abruptly around 1300 CE and terminating in the late 1300s. The exceptional magnitude and duration of this "Great Sea-Ice Anomaly" was previously unknown. The pulse of ice along East Greenland resulted in downstream increases in polar waters and ocean stratification, culminating ~1400 CE and sustained during subsequent centuries.  https://www.selleckchem.com/products/FK-506-(Tacrolimus).html  While consistent with external forcing theories, the onset and development are notably similar to modeled spontaneous abrupt cooling enhanced by sea-ice feedbacks. These results provide evidence that marked climate changes may not require an external trigger.Bacteria control the length of their polysaccharides, which can control cell viability, physiology, virulence, and immune evasion. Polysaccharide chain length affects immunomodulation, but its impact on bacterial physiology and antibiotic susceptibility was unclear. We probed the consequences of truncating the mycobacterial galactan, an essential linear polysaccharide of about 30 residues. Galactan covalently bridges cell envelope layers, with the outermost cell wall linkage point occurring at residue 12. Reducing galactan chain length by approximately half compromises fitness, alters cell morphology, and increases the potency of hydrophobic antibiotics. Systematic variation of the galactan chain length revealed that it determines periplasm size. Thus, glycan chain length can directly affect cellular physiology and antibiotic activity, and mycobacterial glycans, not proteins, regulate periplasm size.Glacial lake outburst floods (GLOFs) are a substantial hazard for downstream communities in vulnerable regions, yet unpredictable triggers and remote source locations make GLOF dynamics difficult to measure and quantify. Here, we revisit a destructive GLOF that occurred in Bhutan in 1994 and apply cross-correlation-based seismic analyses to track the evolution of the GLOF remotely (~100 kilometers from the source region). We use the seismic observations along with eyewitness reports and a downstream gauge station to constrain a numerical flood model and then assess geomorphic change and current state of the unstable lakes via satellite imagery. Coherent seismic energy is evident from 1 to 5 hertz beginning approximately 5 hours before the flood impacted Punakha village, which originated at the source lake and advanced down the valley during the GLOF duration. Our analysis highlights potential benefits of using real-time seismic monitoring to improve early warning systems.Caste differentiation happens early in development to produce gynes as future colony germlines and workers as present colony soma. However, gynes need insemination to become functional queens, a transition that initiates reproductive role differentiation relative to unmated gynes. Here, we analyze the anatomy and transcriptomes of brains during this differentiation process within the reproductive caste of Monomorium pharaonis Insemination terminated brain growth, whereas unmated control gynes continued to increase brain volume. Transcriptomes revealed a specific gene regulatory network (GRN) mediating both brain anatomy changes and behavioral modifications. This reproductive role differentiation GRN hardly overlapped with the gyne-worker caste differentiation GRN, but appears to be also used by distantly related ants where workers became germline individuals after the queen caste was entirely or partially lost. The genes corazonin and neuroparsin A in the anterior neurosecretory cells were overexpressed in individuals with reduced or nonreproductive roles across all four ant species investigated.