Stabilization of β-catenin promotes melanocyte specification at the expense of the Schwann cell lineage

The canonical Wnt/β-catenin pathway governs a multitude of developmental processes in various cell lineages, including the melanocyte lineage. Indeed, β-catenin regulates Mitf-M transcription, the master regulator of this lineage. The first wave of melanocytes to colonize the skin is directly derived from neural crest cells, while the second wave of melanocytes is derived from Schwann-cell precursors (SCPs). We investigated the influence of β-catenin in the development of melanocytes of the first and second waves by generating mice expressing a constitutively active form of β-catenin in cells expressing tyrosinase. Constitutive activation of β-catenin did not affect the development of truncal melanoblasts but led to marked hyperpigmentation of the paws. By activating β-catenin at various stages of development (E8.5-E11.5), we showed that the activation of β-catenin in bipotent SCPs favored melanoblast specification at the expense of Schwann cells in the limbs within a specific temporal window. Furthermore, in vitro hyperactivation of the Wnt/β-catenin pathway, which is required for melanocyte development, induces activation of Mitf-M, in turn repressing FoxD3 expression. In conclusion, β-catenin overexpression promotes SCP cell fate decisions towards the melanocyte lineage.

Electron quantum path control in high harmonic generation via chirp variation of strong laser pulses

The quantum phases of the electron paths driven by an ultrafast laser in high harmonic generation in an atomic gas depends linearly on the instantaneous cycle-averaged laser intensity. Using high laser intensities, a complete single ionisation of the atomic gas may occur before the laser pulse peak. Therefore, high harmonic generation could be localised only in a temporal window at the leading edge of laser pulse envelope. Varying the laser frequency chirp of an intense ultrafast laser pulse, the centre, and the width of the temporal window, that the high harmonic generation phenomenon occurs, could be controlled with high accuracy. This way, both the duration and the phase of the electron trajectories, that generate efficiently high harmonics, is fully controlled. A method of spectral control and selection of the high harmonic extreme ultraviolet light from distinct quantum paths is experimentally demonstrated. Furthermore, a phenomenological numerical model enlightens the physical processes that take place. This novel approach of the electron quantum path selection via laser chirp is a simple and versatile way of controlling the time-spectral characteristics of the coherent extreme ultraviolet light with applications in the fields of attosecond pulses and soft x-ray nano-imaging.

Dynamic Hormone Gradients Regulate Wound-Induced de novo Organ Formation in Tomato Hypocotyl Explants

Plants have a remarkable regenerative capacity, which allows them to survive tissue damage after biotic and abiotic stresses. In this study, we use Solanum lycopersicum ‘Micro-Tom’ explants as a model to investigate wound-induced de novo organ formation, as these explants can regenerate the missing structures without the exogenous application of plant hormones. Here, we performed simultaneous targeted profiling of 22 phytohormone-related metabolites during de novo organ formation and found that endogenous hormone levels dynamically changed after root and shoot excision, according to region-specific patterns. Our results indicate that a defined temporal window of high auxin-to-cytokinin accumulation in the basal region of the explants was required for adventitious root formation and that was dependent on a concerted regulation of polar auxin transport through the hypocotyl, of local induction of auxin biosynthesis, and of local inhibition of auxin degradation. In the apical region, though, a minimum of auxin-to-cytokinin ratio is established shortly after wounding both by decreasing active auxin levels and by draining auxin via its basipetal transport and internalization. Cross-validation with transcriptomic data highlighted the main hormonal gradients involved in wound-induced de novo organ formation in tomato hypocotyl explants.

Effect of Beach-Chair Position on Cerebral Blood Flow in Patients Undergoing Shoulder Surgery—A Preliminary Observational Study

Background Hypotension and cerebral hypoperfusion, commonly encountered in beach-chair position under general anesthesia, carry the risk of neurologic complications. There is a paucity of data on monitoring cerebral perfusion. Our objective was to compare the mean arterial pressure (MAP) and middle cerebral artery velocity (Vmca) in the supine and beach-chair position and estimate its correlation during hypotension. Materials and Methods Twenty ASA class I and II patients undergoing elective shoulder surgery in beach-chair position were included in the study. MAP was measured invasively with the pressure transducer leveled to the phlebostatic axis. Vmca was measured with a 2 MHz transcranial Doppler (TCD) probe through the temporal window. Both MAP and Vmca were measured at baseline after anesthetic induction in the supine position (BL), on assuming the beach-chair position (AP), at steady-state hemodynamics in beach-chair position (P1), whenever there was a drop in MAP > 20% (P2), and on the restoration of MAP (P3). Results A mean decrease in MAP and Vmca by 24.76% and 27.96%, respectively, from supine to beach-chair position with a significant linear correlation between MAP and Vmca along with a Pearsons’ coefficient of 0.77 was seen. A change in MAP of 1 mm of Hg resulted in a change in Vmca by 0.53 cm/sec (p < 0.05). Conclusion A significant decrease in MAP and Vmca was observed in the beach-chair position. TCD could be used as a point-of-care noninvasive technique to reliably assess cerebral perfusion.

CCR5 closes the temporal window for memory linking

Real world memories are formed in a particular context and are not acquired or recalled in isolation. Time is a key variable in the organization of memories, since events experienced close in time are more likely to be meaningfully associated, while those experienced with a longer interval are not. How does the brain segregate events that are temporally distinct? Here, we report that a delayed (12-24h) increase in the expression of the C-C chemokine receptor type 5 (CCR5), an immune receptor well known as a co-receptor for HIV infection, following the formation of a contextual memory, determines the duration of the temporal window for associating or linking that memory with subsequent memories. This delayed CCR5 expression in mouse dorsal CA1 (dCA1) neurons results in a decrease in neuronal excitability, which in turn negatively regulates neuronal memory allocation, thus reducing the overlap between dCA1 memory ensembles. Lowering this overlap affects the ability of one memory to trigger the recall of the other, thus closing the temporal window for memory linking. Remarkably, our findings also show that an age-related increase in CCL5/CCR5 expression leads to impairments in memory linking in aged mice, which could be reversed with a CCR5 knockout and an FDA approved drug that inhibits this receptor, a result with significant clinical implications. All together the findings reported here provide the first insights into the molecular and cellular mechanisms that shape the temporal window for memory linking.

Grid-Based Anomaly Detection of Freight Vehicle Trajectory considering Local Temporal Window

The security travel of freight vehicles is of high societal concern and is the key issue for urban managers to effectively supervise and assess the possible social security risks. With continuous improvements in motion-based technology, the trajectories of freight vehicles are readily available, whose unusual changes may indicate hidden urban risks. Moreover, the increasing high spatial and temporal resolution of trajectories provides the opportunity for the real-time recognition of the abnormal or risky vehicle motion. However, the existing researches mainly focus on the spatial anomaly detection, and there are few researches on the real-time temporal anomaly detection. In this paper, a grid-based algorithm, which combines the spatial and temporal anomaly detection, is proposed for tracing the risk of urban freight vehicles trajectory by considering local temporal window. The travel time probability distribution of vehicle historical trajectory is analyzed to meet the time complexity requirements of real-time anomaly calculation. The developed methodology is applied to a case study in Beijing to demonstrate its accuracy and effectiveness.

Electron quantum path control in high harmonic generation via chirp variation of strong laser pulses

The quantum phases of the electron paths driven by an ultrafast laser in high harmonic generation in an atomic gas depends linearly on the instantaneous cycle-averaged laser intensity. Using high laser intensities, a complete single ionisation of the atomic gas may occur before the laser pulse peak. Therefore, high harmonic generation could be localized only in a temporal window at the leading edge of laser pulse envelope. Varying the laser frequency chirp of an intense ultrafast laser pulse, the centre, and the width of the temporal window, that the high harmonic generation phenomenon occurs, could be controlled with high accuracy. This way, both the duration and the phase of the electron trajectories, that generate efficiently high harmonics, is fully controlled. An accurate and robust method of spectral control and selection of the high harmonic extreme ultraviolet light from distinct quantum paths is experimentally demonstrated. Furthermore, a phenomenological numerical model enlightens the physical processes that take place. This novel approach of the electron quantum path selection via laser chirp is a simple and versatile way of controlling the time-spectral characteristics of the coherent extreme ultraviolet light with future applications in the fields of attosecond pulses and soft x-ray nano-imaging.

Inhibitory gating of coincidence-dependent sensory binding in secondary auditory cortex

Integration of multi-frequency sounds into a unified perceptual object is critical for recognizing syllables in speech. This “feature binding” relies on the precise synchrony of each component’s onset timing, but little is known regarding its neural correlates. We find that multi-frequency sounds prevalent in vocalizations, specifically harmonics, preferentially activate the mouse secondary auditory cortex (A2), whose response deteriorates with shifts in component onset timings. The temporal window for harmonics integration in A2 was broadened by inactivation of somatostatin-expressing interneurons (SOM cells), but not parvalbumin-expressing interneurons (PV cells). Importantly, A2 has functionally connected subnetworks of neurons preferentially encoding harmonic over inharmonic sounds. These subnetworks are stable across days and exist prior to experimental harmonics exposure, suggesting their formation during development. Furthermore, A2 inactivation impairs performance in a discrimination task for coincident harmonics. Together, we propose A2 as a locus for multi-frequency integration, which may form the circuit basis for vocal processing.