Methods for high throughput discovery of fluoroprobes that recognize tau fibril polymorphs.

Aggregation of microtubule-associated protein tau (MAPT/tau) into conformationally distinct fibrils underpins neurodegenerative tauopathies. Fluorescent probes (fluoroprobes), such as thioflavin T (ThT), have been essential tools for studying tau aggregation; however, most of them do not discriminate between amyloid fibril conformations (polymorphs). This gap is due, in part, to a lack of high-throughput methods for screening large, diverse chemical collections.

Chemical Features of Polyanions Modulate Tau Aggregation and Conformational States.

The aggregation of tau into insoluble fibrils is a defining feature of neurodegenerative tauopathies. However, tau has a positive overall charge and is highly soluble; so, polyanions, such as heparin, are typically required to promote its aggregation . There are dozens of polyanions in living systems, and it is not clear which ones might promote this process.

Increased Risk Donors Utilized in Lung Transplantation At A Single Center.

In 2013, the US Public Health Service (PHS) updated guidelines for high-risk donor organs and renamed the category increased risk. We compared survival of patients who received increased risk or non-increased risk donor lungs to determine if PHS designated increased risk donor lungs were an underutilized resource. This retrospective cohort analysis compared survival and utilization rates of increased-risk and non-increased-risk donor lungs used in lung transplantation at a single institution over a period of 8 years (Feb-2012 through Mar-2020).

Anastomotic Suturing Techniques and Their Association With Post-Lung Transplantation Complications.

Introduction: Currently, standard practice is to use the continuous suturing technique on the bronchial anastomosis during lung transplantation. This study used a large cohort to investigate and contrast continuous and interrupted suturing techniques, comparing survival outcomes and occurrence of postoperative bronchial complications to examine if utilization of interrupted suturing has merit.

Methods: Survival outcomes of 740 single-center lung transplant recipients over 8 y (February 2012-March 2020) were compared by suturing techniques: either continuous or interrupted at the bronchial anastomosis.

Lung Transplant Type and Donor Age in Idiopathic Pulmonary Fibrosis: A Single Center Study.

Backgroud: Idiopathic pulmonary fibrosis (IPF) accounts for a marked proportion of diagnoses on the US lung transplant (LTx) list. The effects of single (SLT) versus double LTx (DLT) and lung donor age on survival in IPF remain unclear and were investigated in this study.

Methods: We retrospectively assessed survival of LTx recipients with IPF at a single institution from February 2012-March 2020.

Pathogenic Tau Impairs Axon Initial Segment Plasticity and Excitability Homeostasis.

Dysregulation of neuronal excitability underlies the pathogenesis of tauopathies, including frontotemporal dementia (FTD) with tau inclusions. A majority of FTD-causing tau mutations are located in the microtubule-binding domain, but how these mutations alter neuronal excitability is largely unknown. Here, using CRISPR/Cas9-based gene editing in human pluripotent stem cell (iPSC)-derived neurons and isogenic controls, we show that the FTD-causing V337M tau mutation impairs activity-dependent plasticity of the cytoskeleton in the axon initial segment (AIS).

Complex cis-regulatory landscape of the insulin receptor gene underlies the broad expression of a central signaling regulator.

Insulin signaling plays key roles in development, growth and metabolism through dynamic control of glucose uptake, global protein translation and transcriptional regulation. Altered levels of insulin signaling are known to play key roles in development and disease, yet the molecular basis of such differential signaling remains obscure. Expression of the insulin receptor (InR) gene itself appears to play an important role, but the nature of the molecular wiring controlling InR transcription has not been elucidated.