Guidance cues along the longitudinal axis of the CNS are poorly understood. Wnt proteins attract ascending somatosensory axons to project from the spinal cord to the brain. Here we show that Wnt proteins repel corticospinal tract (CST) axons in the opposite direction. Several Wnt genes were found to be expressed in the mouse spinal cord gray matter, cupping the dorsal funiculus, in an anterior-to-posterior decreasing gradient along the cervical and thoracic cord. Wnts repelled CST axons in collagen gel assays through a conserved high-affinity receptor, Ryk, which is expressed in CST axons. Neonatal spinal cord secretes diffusible repellent(s) in an anterior-posterior graded fashion, with anterior cord being stronger, and the repulsive activity was blocked by antibodies to Ryk (anti-Ryk). Intrathecal injection of anti-Ryk blocked the posterior growth of CST axons. Therefore, Wnt proteins may have a general role in anterior-posterior guidance of multiple classes of axons.

Computational modelling has suggested that at least two counteracting forces are required for establishing topographic maps. Ephrin-family proteins are required for both anterior-posterior and medial-lateral topographic mapping, but the opposing forces have not been well characterized. Wnt-family proteins are recently discovered axon guidance cues. We find that Wnt3 is expressed in a medial-lateral decreasing gradient in chick optic tectum and mouse superior colliculus. Retinal ganglion cell (RGC) axons from different dorsal-ventral positions showed graded and biphasic response to Wnt3 in a concentration-dependent manner. Wnt3 repulsion is mediated by Ryk, expressed in a ventral-to-dorsal decreasing gradient, whereas attraction of dorsal axons at lower Wnt3 concentrations is mediated by Frizzled(s). Overexpression of Wnt3 in the lateral tectum repelled the termination zones of dorsal RGC axons in vivo. Expression of a dominant-negative Ryk in dorsal RGC axons caused a medial shift of the termination zones, promoting medially directed interstitial branches and eliminating laterally directed branches. Therefore, a classical morphogen, Wnt3, acting as an axon guidance molecule, plays a role in retinotectal mapping along the medial-lateral axis, counterbalancing the medial-directed EphrinB1-EphB activity.

Individuals involved in shift work are more likely to become overweight or obese. Appropriate preventive interventions in the organization of shift schedules according to ergonomic criteria would allow shift workers to avoid potential health impairment.

Background: Non-small-cell lung cancer (NSCLC) is a highly lethal disease and an improved understanding of the molecular pathogenesis mechanisms is needed. Results: RACK1 promotes NSCLC via interacting with and activating Smoothened to mediate Gli1-dependent transcription in NSCLC cells. Conclusion: Silencing RACK1 inhibits NSCLC tumorigenicity by blocking Sonic hedgehog signaling pathway. Significance: Highlighting RACK1 serves as a potential biomarker and a therapeutic target of NSCLC.

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BackgroundRabies is invariably a fatal disease. Appropriate wound treatment and prompt rabies post-exposure prophylaxis (PEP) are of great importance to rabies prevention. The objective of this study was to investigate the prevalence and influencing factors of improper wound treatment and delay of rabies PEP after an animal bite in Wuhan, China.MethodologyThis cross-sectional study was conducted among animal bite victims visiting rabies prevention clinics (RPCs). We selected respondents by a multistage sampling technique. A face-to-face interview was conducted to investigate whether the wound was treated properly and the time disparity between injury and attendance to the RPCs. Determinants of improper wound treatment and delay of rabies PEP were identified by a stepwise multivariate logistic regression analysis.Principal findingsIn total, 1,015 animal bite victims (564 women and 451 men) responded to the questionnaire, and the response rate was 93.98%. Overall, 81.2% of animal bite victims treated their wounds improperly after suspected rabies exposure, and 35.3% of animal bite victims delayed the initiation of PEP. Males (OR = 1.871, 95% CI: 1.318–2.656), residents without college education (OR = 1.698, 95% CI: 1.203–2.396), participants liking to play with animals (OR = 1.554, 95% CI: 1.089–2.216), and people who knew the fatality of rabies (OR = 1.577, 95% CI: 1.096–2.270), were more likely to treat wounds improperly after an animal bite. Patients aged 15–44 years (OR = 2.324, 95% CI: 1.457–3.707), who were bitten or scratched by a domestic animal (OR = 1.696, 95% CI: 1.103–2.608) and people who knew the incubation period of rabies (OR = 1.844, 95% CI: 1.279–2.659) were inclined to delay the initiation of PEP.ConclusionsOur investigation shows that improper wound treatment and delayed PEP is common among animal bite victims, although RPCs is in close proximity and PEP is affordable. The lack of knowledge and poor awareness might be the main reason for improper PEP. Educational programs and awareness raising campaigns should be a priority to prevent rabies, especially targeting males, the less educated and those aged 15–44 years.

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