Uncovering the dynamics and consequences of RNA isoform changes during neuronal differentiation.

Static gene expression programs have been extensively characterized in stem cells and mature human cells. However, the dynamics of RNA isoform changes upon cell-state-transitions during cell differentiation, the determinants and functional consequences have largely remained unclear. Here, we established an improved model for human neurogenesis in vitro that is amenable for systems-wide analyses of gene expression.

Integrated electro-coagulation and gravity driven ceramic membrane bioreactor for roofing rainwater purification: Flux improvement and extreme operating case.

The collected roofing rainwater with high water quality and large water volume, can alleviate the crisis of water resources and fit the Low-Impact Development (LID) concept. In this work, a novel water purification technology, Electro-Coagulation coupled with Gravity-Driven Ceramic Membrane Bio-Reactor (EC-GDCMBR) was developed for the roofing rainwater purification under long-term operation (136 days). EC-GDCMBR system not only exhibited the better effluent quality, but also obtained the greater flux (~32 LMH).

Robust differentiation of human pluripotent stem cells into endothelial cells via temporal modulation of ETV2 with modified mRNA.

Human induced pluripotent stem cell (h-iPSC)-derived endothelial cells (h-iECs) have become a valuable tool in regenerative medicine. However, current differentiation protocols remain inefficient and lack reliability. Here, we describe a method for rapid, consistent, and highly efficient generation of h-iECs.

Risk assessment for tailings dams in Brumadinho of Brazil using InSAR time series approach.

Tailings dams are usually ponds bounded by valleys or surrounding topography to store mining or other chemical industrial waste. On 25 January 2019, the collapse of a tailings dam at the Córrego do Feijao iron ore mine (Brumadinho, Minas Gerais, Brazil) released about 12 million m of tailings, killing over 240 people and posing a considerable and ongoing environmental threat. The stability of tailings dam monitoring is very important and in the present paper, a new InSAR (Synthetic Aperture Radar Interferometry) time series approach is proposed to derive ground displacement maps for use in dam safety monitoring.

A multifunctional AAV-CRISPR-Cas9 and its host response.

CRISPR-Cas9 delivery by adeno-associated virus (AAV) holds promise for gene therapy but faces critical barriers on account of its potential immunogenicity and limited payload capacity. Here, we demonstrate genome engineering in postnatal mice using AAV-split-Cas9, a multifunctional platform customizable for genome editing, transcriptional regulation, and other previously impracticable applications of AAV-CRISPR-Cas9. We identify crucial parameters that impact efficacy and clinical translation of our platform, including viral biodistribution, editing efficiencies in various organs, antigenicity, immunological reactions, and physiological outcomes.

Rapid neurogenesis through transcriptional activation in human stem cells.

Advances in cellular reprogramming and stem cell differentiation now enable ex vivo studies of human neuronal differentiation. However, it remains challenging to elucidate the underlying regulatory programs because differentiation protocols are laborious and often result in low neuron yields. Here, we overexpressed two Neurogenin transcription factors in human-induced pluripotent stem cells and obtained neurons with bipolar morphology in 4 days, at greater than 90% purity.

Impaired autophagy in the lipid-storage disorder Niemann-Pick type C1 disease.

Autophagy dysfunction has been implicated in misfolded protein accumulation and cellular toxicity in several diseases. Whether alterations in autophagy also contribute to the pathology of lipid-storage disorders is not clear. Here, we show defective autophagy in Niemann-Pick type C1 (NPC1) disease associated with cholesterol accumulation, where the maturation of autophagosomes is impaired because of defective amphisome formation caused by failure in SNARE machinery, whereas the lysosomal proteolytic function remains unaffected.

System-wide analysis reveals intrinsically disordered proteins are prone to ubiquitylation after misfolding stress.

Damaged and misfolded proteins that are no longer functional in the cell need to be eliminated. Failure to do so might lead to their accumulation and aggregation, a hallmark of many neurodegenerative diseases. Protein quality control pathways play a major role in the degradation of these proteins, which is mediated mainly by the ubiquitin proteasome system.

The yeast ubr1 ubiquitin ligase participates in a prominent pathway that targets cytosolic thermosensitive mutants for degradation.

Mutations causing protein misfolding and proteolysis are associated with many genetic diseases. The degradation of these aberrant proteins typically is mediated by protein-quality control pathways that recognize misfolded domains. Several E3 ubiquitin ligases have been shown to target cytosolic misfolded proteins to the proteasome.

Hul5 HECT ubiquitin ligase plays a major role in the ubiquitylation and turnover of cytosolic misfolded proteins.

Cellular toxicity introduced by protein misfolding threatens cell fitness and viability. Failure to eliminate these polypeptides is associated with numerous aggregation diseases. Several protein quality control mechanisms degrade non-native proteins by the ubiquitin-proteasome system.