The Eph receptor tyrosine kinases (RTKs) are regulators of cell migration and axon guidance. However, our understanding of the molecular mechanisms by which Eph RTKs regulate these processes is still ...incomplete. To understand how Eph receptors regulate axon guidance in Caenorhabditis elegans, we screened for suppressors of axon guidance defects caused by a hyperactive VAB-1/Eph RTK. We identified NCK-1 and WSP-1/N-WASP as downstream effectors of VAB-1. Furthermore, VAB-1, NCK-1, and WSP-1 can form a complex in vitro. We also report that NCK-1 can physically bind UNC-34/Enabled (Ena), and suggest that VAB-1 inhibits the NCK-1/UNC-34 complex and negatively regulates UNC-34. Our results provide a model of the molecular events that allow the VAB-1 RTK to regulate actin dynamics for axon guidance. We suggest that VAB-1/Eph RTK can stop axonal outgrowth by inhibiting filopodia formation at the growth cone by activating Arp2/3 through a VAB-1/NCK-1/WSP-1 complex and by inhibiting UNC-34/Ena activity.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The moments and torques acting on a deforming body determine its stability and maneuverability. For animals, robots, vehicles, and other deforming objects locomoting in liquid or gaseous fluids, ...these fluid moments are challenging to accurately measure during unconstrained motion. Particle image velocimetry and aerodynamic force platforms have the potential to resolve this challenge through the use of control surface integration. These measurement techniques have previously been used to recover fluid forces. Here, we show how control surface integration can similarly be used to recover the 3D fluid moments generated about a deforming body’s center of mass. We first derive a general formulation that can be applied to any body locomoting in a fluid. We then show when and how this formulation can be greatly simplified without loss of accuracy for conditions commonly encountered during fluid experiments, such as for tests done in wind or water channels. Finally, we provide detailed formulations to show how measurements from an aerodynamic force platform can be used to determine the net instantaneous moments generated by a freely flying body. These formulations also apply more generally to other fluid applications, such as underwater swimming or locomotion over water surfaces.
Graphic abstract
Efficient white‐light‐emitting diodes (WLEDs) have been developed using a polyfluorene‐type blue‐emitting conjugated polymer doped with green and red phosphorescent dyes. The emission spectrum of the ...conjugated polymer, which has a very high luminescent efficiency, shows a large spectral overlap with the absorbance of green and red iridium complexes. Also, efficient energy transfer from the conjugated polymer to the iridium complexes is observed. Poly(N‐vinyl carbazole) is used to improve the miscibility between conjugated polymer and iridium complexes because of their poor chemical compatibility and phase separation. A white emission spectrum is easily obtained by varying the contents of the three materials and controlling the phase morphology. Moreover, these WLEDs show a voltage‐independent electroluminescence owing to the threshold and driving voltage of the three materials being similar as a result of energy transfer.
Efficient polymer‐based electrophosphorescent devices for stable white‐light emission (see Figure) take advantage of efficient energy transfer from a conjugated polymer to iridium complexes. Poly(N‐vinylcarbazole) increases energy transfer from the conjugated polymer to the phosphorescent dyes by improving the chemical compatibility; hence, the microphase‐separated morphology of the blend allows blue‐light emission from the polymer, and green and red from the iridium complexes.
This article aims to detail illustrative examples of what equity pedagogy looks like in a classroom in terms of a teacher's interactions with students, and it highlights how these teacher-student ...interactions directly stem from beliefs fundamental to equity pedagogy. If there is belief in equity, educators are more likely to embrace such practices: What we value, we do.
RUNX1/AML1 is among the most commonly mutated genes in human leukemia. Haploinsufficiency of RUNX1 causes familial platelet disorder with predisposition to myeloid malignancies (FPD/MM). However, the ...molecular mechanism of FPD/MM remains unknown. Here we show that murine Runx1(+/-) hematopoietic cells are hypersensitive to granulocyte colony-stimulating factor (G-CSF), leading to enhanced expansion and mobilization of stem/progenitor cells and myeloid differentiation block. Upon G-CSF stimulation, Runx1(+/-) cells exhibited a more pronounced phosphorylation of STAT3 as compared with Runx1(+/+) cells, which may be due to reduced expression of Pias3, a key negative regulator of STAT3 signaling, and reduced physical sequestration of STAT3 by RUNX1. Most importantly, blood cells from a FPD patient with RUNX1 mutation exhibited similar G-CSF hypersensitivity. Taken together, Runx1 haploinsufficiency appears to predispose FPD patients to MM by expanding the pool of stem/progenitor cells and blocking myeloid differentiation in response to G-CSF.
OBJECTIVE: Hospitals provide clinical care to many tuberculosis (TB) patients, but limited linkage with public health programmes is contributing to low TB case detection and rising TB drug ...resistance. We evaluated a hospital-public health collaboration to improve the follow-up of TB
patients initially seen in hospitals.DESIGN: In nine counties in eastern China, we evaluated a collaboration with three interventions: hospitals carried out internet-based reporting and patient referral to the local Center for Disease Control (CDC). The CDC regularly checked on hospital
reporting and referrals and performed active follow-up of reported patients, and a government coordinating group facilitated implementation of collaborative activities.RESULTS: Compared to the pre-intervention period, the percentage of TB suspects and patients needing referral from the
hospitals who arrived in the CDC increased from 59.3% to 83.2% (P < 0.001). This increase was a result of improved hospital reporting (42.5% to 95.3%, P < 0.001), improved referral from hospitals (48.1% to 83.3%, P < 0.001), active CDC follow-up of 82.5% of reported
patients who did not attend CDC by themselves, and successful tracing of 60.8% of these patients. This contributed to a 33% increase in reported smear-positive pulmonary TB cases.CONCLUSION: This model collaboration successfully improved the follow-up of TB patients seen by hospitals,
and contributed to an increase in TB case detection.
The conserved ATM checkpoint kinase and the Mre11 DNA repair complex play essential and overlapping roles in maintaining genomic integrity. We conducted genetic and cytological studies on Drosophila ...atm and mre11 knockout mutants and discovered a telomere defect that was more severe than in any of the non-Drosophila systems studied. In mutant mitotic cells, an average of 30% of the chromosome ends engaged in telomere fusions. These fusions led to the formation and sometimes breakage of dicentric chromosomes, thus starting a devastating breakage-fusion-bridge cycle. Some of the fusions depended on DNA ligase IV, which suggested that they occurred by a nonhomologous end-joining (NHEJ) mechanism. Epistasis analyses results suggest that ATM and Mre11 might also act in the same telomere maintenance pathway in metazoans. Since Drosophila telomeres are not added by a telomerase, our findings support an additional role for both ATM and Mre11 in telomere maintenance that is independent of telomerase regulation.
Animal flight requires aerodynamic power, which is challenging to determine accurately
Existing methods rely on approximate calculations based on wake flow field measurements, inverse dynamics ...approaches, or invasive muscle physiological recordings. In contrast, the external mechanical work required for terrestrial locomotion can be determined more directly by using a force platform as an ergometer. Based on an extension of the recent invention of the aerodynamic force platform, we now present a more direct method to determine the
aerodynamic power by taking the dot product of the aerodynamic force vector on the wing with the representative wing velocity vector based on kinematics and morphology. We demonstrate this new method by studying a slowly flying dove, but it can be applied more generally across flying and swimming animals as well as animals that locomote over water surfaces. Finally, our mathematical framework also works for power analyses based on flow field measurements.
High-pressure equation of state and isentropic sound speed data for fluid silicon to pressures of 2100 GPa (21 Mbar) are reported. Principal Hugoniot measurements were performed using impedance ...matching techniques with α-quartz as the reference. Sound speeds were determined by time correlating imposed shock-velocity perturbations in both the sample (Si) and reference material (α-quartz). A change in shock velocity versus particle velocity ( us–up) slope on the fluid silicon principal Hugoniot is observed at 200 GPa. Density functional theory based quantum molecular dynamics simulations suggest that both an increase in ionic coordination and a 50% increase in average ionization are coincident with this experimentally observed change in slope.
Multiple schedules are effective at decreasing challenging behavior and maintaining alternative behavior at acceptable levels. Currently, no conclusive guidance is available for empirically deriving ...multiple‐schedule components (continuous reinforcement for alternative behavior and extinction for challenging behavior discriminative stimulus and extinction for both alternative and challenging behavior delta stimulus) during the schedule‐thinning process. In the current investigation, we describe a terminal schedule probe method to determine delta stimulus starting points and strategies for subsequent schedule‐thinning progressions to reach caregiver‐informed terminal schedules. We review schedule‐thinning outcomes for a clinical cohort using a consecutive controlled case series approach and report results for two groups: One group included applications of terminal probe thinning (n = 24), and the other involved traditional dense‐to‐lean thinning (n = 18). Outcomes suggest that the terminal schedule probe method produced effective treatments with less resurgence of challenging behavior and leaner, more feasible, multiple schedules.
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