iPSC-induced neurons with the V337M MAPT mutation are selectively vulnerable to caspase-mediated cleavage of tau and apoptotic cell death.

Background: Tau post-translational modifications (PTMs) result in the gradual build-up of abnormal tau and neuronal degeneration in tauopathies, encompassing variants of frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Tau proteolytically cleaved by active caspases, including caspase-6, may be neurotoxic and prone to self-aggregation. Also, our recent findings show that caspase-6 truncated tau represents a frequent and understudied aspect of tau pathology in AD in addition to phospho-tau pathology.

Asthma patients' and physicians' perspectives on the burden and management of asthma: Post-hoc analysis of APPaRENT 1 and 2 to assess predictors of treatment adherence.

Introduction: Patient adherence to maintenance medication is critical for improving clinical outcomes in asthma and is a recommended guiding factor for treatment strategy. Previously, the APPaRENT studies assessed patient and physician perspectives on asthma care; here, a post-hoc analysis aimed to identify patient factors associated with good adherence and treatment prescription patterns.

Methods: APPaRENT 1 and 2 were cross-sectional online surveys of 2866 adults with asthma and 1883 physicians across Argentina, Australia, Brazil, Canada, China, France, Italy, Mexico, and the Philippines in 2020-2021.

High-throughput optofluidic screening of single B cells identifies novel cross-reactive antibodies as inhibitors of uPAR with antibody-dependent effector functions.

The urokinase-type plasminogen activator receptor (uPAR) is an essential regulator for cell signaling in tumor cell proliferation, adhesion, and metastasis. The ubiquitous nature of uPAR in many aggressive cancer types makes uPAR an attractive target for immunotherapy. Here, we present a rapid and successful workflow for developing cross-reactive anti-uPAR recombinant antibodies (rAbs) using high-throughput optofluidic screening of single B-cells from human uPAR-immunized mice.

Caspase-6-cleaved tau is relevant in Alzheimer's disease and marginal in four-repeat tauopathies: Diagnostic and therapeutic implications.

Aim: Tau truncation (tr-tau) by active caspase-6 (aCasp-6) generates tau fragments that may be toxic. Yet the relationship between aCasp-6, different forms of tr-tau and hyperphosphorylated tau (p-tau) accumulation in human brains with Alzheimer's disease (AD) and other tauopathies remains unclear.

Methods: We generated two neoepitope monoclonal antibodies against tr-tau sites (D402 and D13) targeted by aCasp-6.

Development and characterization of human monoclonal antibodies that neutralize multiple TGFβ isoforms.

Transforming growth factor (TGF)β levels are elevated in, and drive the progression of, numerous disease states such as advanced metastatic cancer and systemic and ocular fibrosis. There are 3 main isoforms, TGFβ1, 2, and 3. As multiple TGFβ isoforms are involved in disease processes, maximal therapeutic efficacy may require neutralization of 2 or more of the TGFβ isoforms.

p14ARF is a component of the p53 response following ionizing irradiation of normal human fibroblasts.

Ionizing radiation leads to rapid stabilization and activation of the p53 tumor suppressor. Previous reports demonstrate that murine p19ARF cooperates with p53 in the cellular response to gamma irradiation. Here, we show that endogenous ARF sequentially interacts with p53 and MDM2 following irradiation of primary human and mouse embryonic fibroblasts.