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The cardiac and hematopoietic progenitors (CPs and HPs, respectively) in the mesoderm ultimately form a well-organized circulation system, but mechanisms that reconcile their development remain elusive. We found that activating transcription factor 3 (atf3) was highly expressed in the CPs, HPs, and mesoderm, in zebrafish. The atf3 -/- mutants exhibited atrial dilated cardiomyopathy and a high ratio of immature myeloid cells. These manifestations were primarily caused by the blockade of differentiation of both CPs and HPs within the anterior lateral plate mesoderm. Mechanistically, Atf3 targets cebpγ to repress slc2a1a-mediated glucose utilization. The high rate of glucose metabolism in atf3 -/- mutants inhibited the differentiation of progenitors by changing the redox state. Therefore, atf3 could provide CPs and HPs with metabolic adaptive capacity to changes in glucose levels. Our study provides new insights into the role of atf3 in the coordination of differentiation of CPs and HPs by regulating glucose metabolism.Alzheimer's disease (AD) is a neurodegenerative disorder that causes cognitive decline, memory loss, and inability to perform everyday functions. Hallmark features of AD-including generation of amyloid plaques, neurofibrillary tangles, gliosis, and inflammation in the brain-are well defined; however, the cause of the disease remains elusive. Growing evidence implicates pathogens in AD development, with herpes simplex virus type I (HSV-1) gaining increasing attention as a potential causative agent. Here, we describe a multidisciplinary approach to produce physiologically relevant human tissues to study AD using human-induced neural stem cells (hiNSCs) and HSV-1 infection in a 3D bioengineered brain model. We report a herpes-induced tissue model of AD that mimics human disease with multicellular amyloid plaque-like formations, gliosis, neuroinflammation, and decreased functionality, completely in the absence of any exogenous mediators of AD. This model will allow for future studies to identify potential downstream drug targets for treating this devastating disease.Presently, the Indian Ocean (IO) resides in a climate state that prevents strong year-to-year climate variations. This may change under greenhouse warming, but the mechanisms remain uncertain, thus limiting our ability to predict future changes in climate extremes. Using climate model simulations, we uncover the emergence of a mode of climate variability capable of generating unprecedented sea surface temperature and rainfall fluctuations across the IO. https://www.selleckchem.com/products/SGI-1776.html This mode, which is inhibited under present-day conditions, becomes active in climate states with a shallow thermocline and vigorous upwelling, consistent with the predictions of continued greenhouse warming. These predictions are supported by modeling and proxy evidence of an active mode during glacial intervals that favored such a state. Because of its impact on hydrological variability, the emergence of such a mode would become a first-order source of climate-related risks for the densely populated IO rim.Hundreds of YouTube videos show people running on cornstarch suspensions demonstrating that dense shear thickening suspensions solidify under impact. Such processes are mimicked by impacting and pulling out a plate from the surface of a thickening cornstarch suspension. Here, using both experiments and simulations, we show that applying fast oscillatory shear transverse to the primary impact or extension directions tunes the degree of solidification. The forces acting on the impacting surface are modified by varying the dimensionless ratio of the orthogonal shear to the compression and extension flow rate. Simulations show varying this parameter changes the number of particle contacts governing solidification. To demonstrate this strategy in an untethered context, we show the sinking speed of a cylinder dropped onto the suspension varies markedly by changing this dimensionless ratio. These results suggest applying orthogonal shear while people are running on cornstarch would de-solidify the suspension and cause them to sink.The Tibetan Plateau exerts a major influence on Asian climate, but its long-term environmental history remains largely unknown. We present a detailed record of vegetation and climate changes over the past 1.74 million years in a lake sediment core from the Zoige Basin, eastern Tibetan Plateau. Results show three intervals with different orbital- and millennial-scale features superimposed on a stepwise long-term cooling trend. The interval of 1.74-1.54 million years ago is characterized by an insolation-dominated mode with strong ~20,000-year cyclicity and quasi-absent millennial-scale signal. The interval of 1.54-0.62 million years ago represents a transitional insolation-ice mode marked by ~20,000- and ~40,000-year cycles, with superimposed millennial-scale oscillations. The past 620,000 years are characterized by an ice-driven mode with 100,000-year cyclicity and less frequent millennial-scale variability. A pronounced transition occurred 620,000 years ago, as glacial cycles intensified. These new findings reveal how the interaction of low-latitude insolation and high-latitude ice-volume forcing shaped the evolution of the Tibetan Plateau climate.Sensory processing requires mechanisms of fast coincidence detection to discriminate synchronous from asynchronous inputs. Spike threshold adaptation enables such a discrimination but is ineffective in transmitting this information to the network. We show here that presynaptic axonal sodium channels read and transmit precise levels of input synchrony to the postsynaptic cell by modulating the presynaptic action potential (AP) amplitude. As a consequence, synaptic transmission is facilitated at cortical synapses when the presynaptic spike is produced by synchronous inputs. Using dual soma-axon recordings, imaging, and modeling, we show that this facilitation results from enhanced AP amplitude in the axon due to minimized inactivation of axonal sodium channels. Quantifying local circuit activity and using network modeling, we found that spikes induced by synchronous inputs produced a larger effect on network activity than spikes induced by asynchronous inputs. Therefore, this input synchrony-dependent facilitation may constitute a powerful mechanism, regulating synaptic transmission at proximal synapses.