Molecular Weight Dependence of Polymersome Membrane Elasticity and Stability

Vesicles prepared in water from a series of diblock copolymers and termed "polymersomes" are physically characterized. With increasing molecular weight $\bar{M}_n$, the hydrophobic core thickness $d$ for the self-assembled bilayers of polyethyleneoxide - polybutadiene (PEO-PBD) increases up to 20 $nm$ - considerably greater than any previously studied lipid system. The mechanical responses of these membranes, specifically, the area elastic modulus $K_a$ and maximal areal strain $\alpha_c$ are measured by micromanipulation. As expected for interface-dominated elasticity, $K_a$ ($\simeq$ 100 $pN/nm$) is found to be independent of $\bar{M}_n$. Related mean-field ideas also predict a limiting value for $\alpha_c$ which is universal and about 10-fold above that typical of lipids. Experiments indeed show $\alpha_c$ generally increases with $\bar{M}_n$, coming close to the theoretical limit before stress relaxation is opposed by what might be chain entanglements at the highest $\bar{M}_n$. The results highlight the interfacial limits of self-assemblies at the nano-scale.Comment: 16 pages, 5 figures, and 1 tabl

Post-Exposure Protection in Mice against Sudan Virus by a Two Antibody Cocktail

Sudan virus (SUDV) and Ebola viruses (EBOV) are both members of the Ebolavirus genus and have been sources of epidemics and outbreaks for several decades. We present here the generation and characterization of cross-reactive antibodies to both SUDV and EBOV, which were produced in a cell-free system and protective against SUDV in mice. A non-human primate, cynomolgus macaque, was immunized with viral-replicon particles expressing the glycoprotein of SUDV-Boniface (8A). Two separate antibody fragment phage display libraries were constructed after four immunogen injections. Both libraries were screened first against the SUDV and a second library was cross-selected against EBOV-Kikwit. Sequencing of 288 selected clones from the two distinct libraries identified 58 clones with distinct VH and VL sequences. Many of these clones were cross-reactive to EBOV and SUDV and able to neutralize SUDV. Three of these recombinant antibodies (X10B1, X10F3, and X10H2) were produced in the scFv-Fc format utilizing a cell-free production system. Mice that were challenged with SUDV-Boniface receiving 100µg of the X10B1/X10H2 scFv-Fc combination 6 and 48-h post-exposure demonstrated partial protection individually and complete protection as a combination. The data herein suggests these antibodies may be promising candidates for further therapeutic development

A call for comparative effectiveness research to learn whether routine clinical care decisions can protect from dementia and cognitive decline

Common diseases like diabetes, hypertension, and atrial fibrillation are probable risk factors for dementia, suggesting that their treatments may influence the risk and rate of cognitive and functional decline. Moreover, specific therapies and medications may affect long-term brain health through mechanisms that are independent of their primary indication. While surgery, benzodiazepines, and anti-cholinergic drugs may accelerate decline or even raise the risk of dementia, other medications act directly on the brain to potentially slow the pathology that underlies Alzheimer's and other dementia. In other words, the functional and cognitive decline in vulnerable patients may be influenced by the choice of treatments for other medical conditions. Despite the importance of these questions, very little research is available. The Alzheimer's Drug Discovery Foundation convened an advisory panel to discuss the existing evidence and to recommend strategies to accelerate the development of comparative effectiveness research on how choices in the clinical care of common chronic diseases may protect from cognitive decline and dementia