Human cortical organoids expose a differential function of GSK3 on cortical neurogenesis

The regulation of the proliferation and polarity of neural progenitors is crucial for the development of the brain cortex. Animal studies have implicated glycogen synthase kinase 3 (GSK3) as a pivotal regulator of both proliferation and polarity, yet the functional relevance of its signaling for the unique features of human corticogenesis remains to be elucidated. We harnessed human cortical brain organoids to probe the longitudinal impact of GSK3 inhibition through multiple developmental stages. Chronic GSK3 inhibition increased the proliferation of neural progenitors and caused massive derangement of cortical tissue architecture. Single-cell transcriptome profiling revealed a direct impact on early neurogenesis and uncovered a selective role of GSK3 in the regulation of glutamatergic lineages and outer radial glia output. Our dissection of the GSK3-dependent transcriptional network in human corticogenesis underscores the robustness of the programs determining neuronal identity independent of tissue architecture

Current Estimates for HIV-1 Production Imply Rapid Viral Clearance in Lymphoid Tissues

It has recently been estimated that a single HIV-1 infected cell produces between and more than viral particles over its life span. Since body-wide estimates of the ratio of free virus to productively infected cells are smaller than and much smaller than , individual virions must be cleared rapidly. This seems difficult to reconcile with the fact that most of the total body virus is trapped on follicular dendritic cells where it can survive for many months. It has also been difficult to reconcile the vast difference in the rates at which the virus is cleared from the blood in rhesus macaques and in chronically infected patients. Here we attempt to reconcile these seemingly contradictory observations by considering the virion clearance rate in various organs and the virion exchange rates between them. The main results are that the per capita clearance rate of free virus in lymphoid tissue should be fast, the virion exchange rate between lymphoid tissue and the blood should be slow, and the comparatively slow previous estimates for the virion clearance rate from the blood correspond to the rate of virion efflux from the blood to other organs where the virus is ultimately cleared

An empirical investigation of performance overhead in cross-platform mobile development frameworks

The heterogeneity of the leading mobile platforms in terms of user interfaces, user experience, programming language, and ecosystem have made cross-platform development frameworks popular. These aid the creation of mobile applications – apps – that can be executed across the target platforms (typically Android and iOS) with minimal to no platform-specific code. Due to the cost- and time-saving possibilities introduced through adopting such a framework, researchers and practitioners alike have taken an interest in the underlying technologies. Examining the body of knowledge, we, nonetheless, frequently encounter discussions on the drawbacks of these frameworks, especially with regard to the performance of the apps they generate. Motivated by the ongoing discourse and a lack of empirical evidence, we scrutinised the essential piece of the cross-platform frameworks: the bridge enabling cross-platform code to communicate with the underlying operating system and device hardware APIs. The study we present in the article benchmarks and measures the performance of this bridge to reveal its associated overhead in Android apps. The development of the artifacts for this experiment was conducted using five cross-platform development frameworks to generate Android apps, in addition to a baseline native Android app implementation. Our results indicate that – for Android apps – the use of cross-platform frameworks for the development of mobile apps may lead to decreased performance compared to the native development approach. Nevertheless, certain cross-platform frameworks can perform equally well or even better than native on certain metrics which highlights the importance of well-defined technical requirements and specifications for deliberate selection of a cross-platform framework or overall development approach