Implantable and Degradable Thermoplastic Elastomer.

Biodegradable and implantable materials having elastomeric properties are highly desirable for many biomedical applications. Here, we report that poly(lactide)--poly(β-methyl-δ-valerolactone)--poly(lactide) (PLA-PβMδVL-PLA), a thermoplastic triblock poly(α-ester), has combined favorable properties of elasticity, biodegradability, and biocompatibility. This material exhibits excellent elastomeric properties in both dry and aqueous environments.

A conserved arginine in NS5 binds genomic 3' stem-loop RNA for primer-independent initiation of flavivirus RNA replication.

The commitment to replicate the RNA genome of flaviviruses without a primer involves RNA-protein interactions that have been shown to include the recognition of the stem-loop A (SLA) in the 5' untranslated region (UTR) by the nonstructural protein NS5. We show that DENV2 NS5 arginine 888, located within the carboxy-terminal 18 residues, is completely conserved in all flaviviruses and interacts specifically with the top-loop of 3'SL in the 3'UTR which contains the pentanucleotide 5'-CACAG-3' previously shown to be critical for flavivirus RNA replication. We present virological and biochemical data showing the importance of this Arg 888 in virus viability and de novo initiation of RNA polymerase activity in vitro.

Optimal flexibility of the linker region of Zika virus NS5 methyltransferase-polymerase is critical for virus replication.

The flavivirus NS5 protein contains an N-terminal methyl-transferase (MTase) connected through a flexible linker with a C-terminal RNA-dependent RNA-polymerase (RdRp) domain, that work cooperatively to replicate and methylate the viral genome. In this study we probed the importance of an evolutionary-conserved hydrophobic residue (Val266) located at the start of the ten-residue interdomain linker of Zika virus (ZIKV) NS5. In flavivirus NS5 crystal structures, the start of the linker forms a 3 helix when NS5 adopts a compact conformation, but becomes disordered or extended in open conformations.

Deep Learning to Decipher the Progression and Morphology of Axonal Degeneration.

Axonal degeneration (AxD) is a pathological hallmark of many neurodegenerative diseases. Deciphering the morphological patterns of AxD will help to understand the underlying mechanisms and develop effective therapies. Here, we evaluated the progression of AxD in cortical neurons using a novel microfluidic device together with a deep learning tool that we developed for the enhanced-throughput analysis of AxD on microscopic images.

A Preclinical Safety Study of Thyroid Hormone Instilled into the Lungs of Healthy Rats-an Investigational Therapy for ARDS.

Acute respiratory distress syndrome (ARDS) is a severe, life-threatening form of respiratory failure characterized by pulmonary edema, inflammation, and hypoxemia due to reduced alveolar fluid clearance (AFC). Alveolar fluid clearance is required for recovery and effective gas exchange, and higher rates of AFC are associated with reduced mortality. Thyroid hormones play multiple roles in lung function, and L-3,5,3'-triiodothyronine (T3) has multiple effects on lung alveolar type II cells.