AbstractmRNA structure is important for post-transcriptional regulation, largely because it affects binding of trans-acting factors 1 . However, little is known about the in vivo structure of full-length mRNAs. Here we present hiCLIP, a high-throughput technique to identify RNA secondary structures interacting with RNA-binding proteins (RBPs) in vivo. Using this technique to investigate RNA structures bound by Staufen 1 (STAU1), we uncover a dominance of intra-molecular RNA duplexes, a depletion of duplexes from coding regions of highly translated mRNAs, an unforeseen prevalence of long-range duplexes in 3′ untranslated regions (UTRs), and a decreased incidence of SNPs in duplex-forming regions. We also discover a duplex spanning 858nts in the 3′ UTR of the X-box binding Protein 1 (XBP1) mRNA that regulates its cytoplasmic splicing and stability. Our study reveals the fundamental role of mRNA secondary structures in gene regulation and introduces hiCLIP as a widely applicable method for discovering novel, especially long-range, RNA duplexes.

Background and Purpose-We evaluated recanalization rates, clinical outcomes, and safety when manual aspiration thrombectomy is used in conjunction with other thrombolytic modalities in a consecutive case series of patients with large vessel intracranial occlusion. Methods-We conducted a retrospective review of a prospectively acquired acute endovascular stroke database. Manual aspiration thrombectomy was carried out with Distal Access and Penumbra reperfusion catheters of different sizes placed in the thrombus and aspirated with a syringe. Results-We identified 191 patients: Occlusion locations were as follows: M1% to 50%, M2% to 10%, internal carotid artery terminus 25%, and vertebrobasilar 15%. Median treatment duration was 90 minutes. Recanalization results were Thrombolysis in Myocardial Ischemia 2/3 93%, Thrombolysis in Myocardial Ischemia 3 27%, Thrombolysis In Cerebral Infarction 2a/2b/3 91%, Thrombolysis In Cerebral Infarction 2b/3 71%, and Thrombolysis In Cerebral Infarction 3 25%. Larger catheters were associated with higher recanalization rates. Parenchymal hematoma rate was 13.6%. The favorable outcome (90-day modified Rankin Scale Յ2) rate was 54%. Mortality at 90 days was 25%. Conclusions-Manual aspiration thrombectomy is a useful addition to the armamentarium of endovascular treatment modalities for acute stroke.

Since the reprogramming of adult human terminally differentiated somatic cells into induced pluripotent stem cells (hiPSCs) became a reality in 2007, only eight years have passed. Yet over this relatively short period, myriad experiments have revolutionized previous stem cell dogmata. The tremendous promise of hiPSC technology for regenerative medicine has fuelled rising expectations from both the public and scientific communities alike. In order to effectively harness hiPSCs to uncover fundamental mechanisms of disease, it is imperative to first understand the developmental neurobiology underpinning their lineage restriction choices in order to predictably manipulate cell fate to desired derivatives. Significant progress in developmental biology provides an invaluable resource for rationalising directed differentiation of hiPSCs to cellular derivatives of the nervous system. In this paper we begin by reviewing core developmental concepts underlying neural induction in order to provide context for how such insights have guided reductionist in vitro models of neural conversion from hiPSCs. We then discuss early factors relevant in neural patterning, again drawing upon crucial knowledge gained from developmental neurobiological studies. We conclude by discussing open questions relating to these concepts and how their resolution might serve to strengthen the promise of pluripotent stem cells in regenerative medicine.

Background Parkinson's disease (PD) affects males more than females. The reasons for the gender differences in PD prevalence remain unclear. Objective The objective of this systematic review and meta‐analysis was to update the overall male/female prevalence ratios (OPR). Methods We updated previous work by searching MEDLINE, SCOPUS, and OVID for articles reporting PD prevalence for both genders between 2011 and 2021. We calculated OPRs and investigated heterogeneity in effect estimates. Results We included 19 new articles and 13 articles from a previously published meta‐analysis. The OPR was 1.18, 95% CI, [1.03, 1.36]. The OPR was lowest in Asia and appeared to be decreasing over time. Study design, national wealth, and participant age did not explain OPR heterogeneity. Conclusion Gender differences in PD prevalence may not be as stark as previously thought. Studies are needed to understand the role of other determinants of gender differences in PD prevalence.