Sonogenetic control of mammalian cells using exogenous Transient Receptor Potential A1 channels.

Ultrasound has been used to non-invasively manipulate neuronal functions in humans and other animals. However, this approach is limited as it has been challenging to target specific cells within the brain or body. Here, we identify human Transient Receptor Potential A1 (hsTRPA1) as a candidate that confers ultrasound sensitivity to mammalian cells. Ultrasound-evoked gating of hsTRPA1 specifically requires its N-terminal tip region and cholesterol interactions; and target cells with an intact actin cytoskeleton, revealing elements of the sonogenetic mechanism. Next, we use calcium imaging and electrophysiology to show that hsTRPA1 potentiates ultrasound-evoked responses in primary neurons. Furthermore, unilateral expression of hsTRPA1 in mouse layer V motor cortical neurons leads to c-fos expression and contralateral limb responses in response to ultrasound delivered through an intact skull. Collectively, we demonstrate that hsTRPA1-based sonogenetics can effectively manipulate neurons within the intact mammalian brain, a method that could be used across species.

Evolution of COVID-19 Pregnancies Treated With Nitazoxanide in a Third-Level Hospital.

Background Nitazoxanide shows adequate in vitro activity against coronavirus. The aim of this study was to describe the behavior of coronavirus disease 2019 (COVID-19) in pregnant women treated with nitazoxanide. Methodology This cross-sectional study included the files of COVID-19 positive pregnant women treated with nitazoxanide 500 mg every 6 hours, levofloxacin every 12 hours, and clarithromycin 500 mg every 12 hours. Results The data of 51 women (mean age: 27.4 ± 7.2 years) were analyzed. Eleven (21.56%) patients had to receive medical attention in the intensive care unit. There were 22 (43.13%) preterm deliveries, 21 by cesarean and one by vaginal delivery. The medical attention of this population was as follows: 31 cesareans, five vaginal deliveries, nine still pregnant, two requiring manual vacuum aspiration, two ectopic pregnancies, one requiring curettage, and one requiring hysterotomy. There were seven (13.72%) cases of preeclampsia, and there were two (3.92%) deaths. Conclusion Nitazoxanide prescription could be an option against COVID-19 in pregnancy due to its safety profile.

The G2-to-M Transition Is Ensured by a Dual Mechanism that Protects Cyclin B from Degradation by Cdc20-Activated APC/C.

In the eukaryotic cell cycle, a threshold level of cyclin B accumulation triggers the G2-to-M transition, and subsequent cyclin B destruction triggers mitotic exit. The anaphase-promoting complex/cyclosome (APC/C) is the E3 ubiquitin ligase that, together with its co-activator Cdc20, targets cyclin B for destruction during mitotic exit. Here, we show that two pathways act in concert to protect cyclin B from Cdc20-activated APC/C in G2, in order to enable cyclin B accumulation and the G2-to-M transition. The first pathway involves the Mad1-Mad2 spindle checkpoint complex, acting in a distinct manner from checkpoint signaling after mitotic entry but employing a common molecular mechanism-the promotion of Mad2-Cdc20 complex formation. The second pathway involves cyclin-dependent kinase phosphorylation of Cdc20, which is known to reduce Cdc20's affinity for the APC/C. Cooperation of these two mechanisms, which target distinct APC/C binding interfaces of Cdc20, enables cyclin B accumulation and the G2-to-M transition.