SARS-CoV-2 infects human brain organoids causing cell death and loss of synapses that can be rescued by treatment with Sofosbuvir.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which was rapidly declared a pandemic by the World Health Organization (WHO). Early clinical symptomatology focused mainly on respiratory illnesses. However, a variety of neurological manifestations in both adults and newborns are now well-documented.

Heads Up! Interlinked Amyloidogenic and Axonal Transport Pathways in Concussion-Induced Neurodegeneration.

Mild traumatic brain injury (mTBI), a condition in which brain function is transiently disrupted by a mechanical force, is a major risk factor for developing Alzheimer's disease (AD) and other neurodegenerative conditions. In this commentary, we summarize recent findings in human neurons derived from induced pluripotent stem cells, detailing early neuronal events following mild injury that may seed future neurodegeneration. In particular, we discuss interlinked relationships between mTBI and several biological pathways hypothesized to underlie AD progression, including amyloidogenic cleavage of amyloid precursor protein (APP), impairment of axonal transport, and the development of APP-associated axonal swellings.

Amyloidogenic Processing of Amyloid Precursor Protein Drives Stretch-Induced Disruption of Axonal Transport in hiPSC-Derived Neurons.

Traumatic brain injury (TBI) results in disrupted brain function following impact from an external force and is a risk factor for sporadic Alzheimer's disease (AD). Although neurologic symptoms triggered by mild traumatic brain injuries (mTBI), the most common form of TBI, typically resolve rapidly, even an isolated mTBI event can increase the risk to develop AD. Aberrant accumulation of amyloid β peptide (Aβ), a cleaved fragment of amyloid precursor protein (APP), is a key pathologic outcome designating the progression of AD following mTBI and has also been linked to impaired axonal transport.

Analysis of Clonal Composition in Human iPSC and ESC and Derived 2D and 3D Differentiated Cultures.

Human induced pluripotent and embryonic stem cell cultures (hiPSC/hESC) are phenotypically heterogeneous and prone to clonal deviations during subculturing and differentiation. Clonal deviations often emerge unnoticed, but they can change the biology of the cell culture with a negative impact on experimental reproducibility. Here, we describe a computational workflow to profile the bulk clonal composition in a hiPSC/hESC culture that can also be used to infer clonal deviations.

Super-Enhancer Redistribution as a Mechanism of Broad Gene Dysregulation in Repeatedly Drug-Treated Cancer Cells.

Cisplatin is an antineoplastic drug administered at suboptimal and intermittent doses to avoid life-threatening effects. Although this regimen shortly improves symptoms in the short term, it also leads to more malignant disease in the long term. We describe a multilayered analysis ranging from chromatin to translation-integrating chromatin immunoprecipitation sequencing (ChIP-seq), global run-on sequencing (GRO-seq), RNA sequencing (RNA-seq), and ribosome profiling-to understand how cisplatin confers (pre)malignant features by using a well-established ovarian cancer model of cisplatin exposure.