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

Prostatic basal cell carcinoma treated by chemoradiation with weekly cisplatine: case report and literature review

Abstract Background Basal cell carcinoma of the prostate is a relatively rare entity. Their evolution is characterized by the frequency of local and/or distant relapses. Due to their rarity, the treatment is not consensual in the literature. We report here a case of Basal cell carcinoma of the prostate in a 40-year-old patient. Case presentation Our patient initially presented an obstructive lower urinary tract symptoms with a normal initial level of prostate specific antigen (PSA) test (3.5 ng/m). The transurethral resection of the prostate (TURP) was in favor of a prostatic basal cell carcinoma with its specific anatomopathological and immunohistochemical characteristics. The prostatic MRI and thoraco-abdominal CT realized after the TURP revealed a tumoral lesion of the prostatic peripheral zone with extra-capsular extension combined with right seminal vesicle invasion and a suggestion of posterior bladder wall adherence. No evidence of visceral or nodal metastases at this point. Considering the tumor being locally advanced, a concurrent chemoradiotherapy with intensity modulated technique was indicated after a multidisciplinary meeting with a 70 Gy total target dose delivered in 35 fractions and weekly Cisplatin. A year and a half after, he developed a cerebellous metastases revealed by intracranial hypertension with no other visceral lesion and complete local remission with the disappearance of the lower urinary tract symptoms and the pain and the appearance of a prostatic atrophy. The PSA level was still on the upper limit of normal. He underwent metastasectomy, and the anatomopathological study was in favor of a cerebellous metastasis of the known BCC. The patient presented postoperatively paraparesis of lower limbs with balance problems for which he was placed in palliative care with indication of postoperative radiation therapy in case of improvement of his general condition. He did not recover and deceased three months later. Conclusions The prostatic basal cell carcinoma is a rare aggressive entity often non-evoked at the clinical or radiological stages because of its unspecific appearance. The diagnostic of these tumors is based on histological examination and a large immunohistochemistry panel. Given its scarity, very few data is available for locally advanced non-metastatic stages treated by radiation therapy. We assess here a good local response with concurrent chemoradiation therapy

Are CD4 and Fas peptide identities of gp120 relevant to the molecular basis of AIDS pathogenesis? - A model for HIV1-induced immunopathogenesis

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

A prophylactic and therapeutic AIDS vaccine containing as a component the innocuous Tat toxoid

Extracellular Tat can act as a viral toxin on uninfected cells of different tissues, including the CNS and the immune system, thus in order to immunize humans against Tat we have prepared a biologically inactivated but immunogenic Tat (Tat Toxoid). Tat Toxoid is not toxic in mice even at high doses. It triggers high levels of specific Tat Abs in the mouse and rabbit. Furthermore, in humans Tat Toxoid immunization was safe and induced in seronegatives persistent high levels of Tat Abs and in immunodeficient patients a significant rise of these specific Abs. Facing acute HIV-1 infection, the presence of high level of circulating Tat Abs promoted by Tat Toxoid vaccine should prevent Tat-induced immunosuppression and allow anti-HIV-1 cellular response to develop. As a consequence, early release of beta-chemokines could enhance host resistance towards HIV-1, and, in infected people, inhibit viral replication and evolution towards AID

Repair of the in vitro HIV-1-induced immunosuppression and blockade of the generation of functional suppressive CD8 cells by anti-alpha interferon and anti-Tat antibodies

The acute human immunodeficiency virus type 1 (HIV-1) infection of activated peripheral blood mononuclear cells (PBMCs) from normal donors results in inhibition of cell proliferation and generation of functional suppressive T cells. Cultured HIV-1 infected PBMCs but not uninfected PBMCs, following irradiation, can inhibit the proliferation of antigen-activated autologous T cells in a dose-dependent way. CD8' cell subpopulation is responsible for this inhibition. The presence of anti-alpha interferon (IFNα) and anti-Tat antibodies in the culture medium counteracts the HIV-1-induced immunosuppression and prevents the generation of suppressive T cells by these PBMCs. The reported data should have major implications for strategies of AIDS treatment which, in association with antiviral drugs, aim at targetting immune disorders.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An easy route to synthesize high-quality black phosphorus from amorphous red phosphorus

The development of an easy and efficient process for producing black phosphorus (BP) remains a bottleneck for the use of BP in large-scale applications. In this work, we present a simple, potentially scalable, and economically viable method for the preparation of high-quality BP from amorphous red phosphorus. BP was synthesized under low pressure and temperature conditions from red phosphorus via the addition of small quantities of copper, tin, and tin(IV) iodide. Characterization by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrometry (EDX), high-resolution transmission electron microscopy (HR-TEM), and Raman spectroscopy were performed to confirm the high quality and purity of the formed BP