Polyvalent Hybrid Virus-Like Nanoparticles with Displayed Heparin Antagonist Peptides.

The potential applications for nanomaterials continue to grow as new materials are developed and environmental and safety concerns are more adequately addressed. In particular, virus-like particles (VLPs) have myriad applications in medicine and biology, exploiting both the reliable, symmetric self-assembly mechanism and the ability to take advantage of surface functionalities that may be appropriately modified through mutation or bioconjugation. Herein we describe the design and application of hybrid VLPs for use as potent heparin antagonists, providing an alternative to the toxic heparin antidote protamine. A two-plasmid system was utilized to generate VLPs that contain both the wild-type coat protein and a second coat protein with either a C- or N-terminal cationic peptide extension (4-28 amino acids). Incorporation of the modified coat proteins varied from 8 to 31%, while activated partial thromboplastin time (APTT) assays revealed a range of the heparin antagonist activity. Notably, when examined on the basis of the quantity of peptide delivered due to the varied incorporation rates, it appeared that the VLPs largely followed a similar trend, with the quantity of peptide delivered more closely correlating with heparin antagonist activity. The particle with the highest incorporation rate and best antiheparin activity displayed the C-terminal peptide ARK2A2KA, which corresponds to the Cardin-Weintraub consensus sequence for binding to glycosaminoglycans. Analysis of this particle using heparin affinity chromatography with fraction collection revealed that particles eluting at higher salt concentration had a greater proportion of peptide incorporation. Preliminary dual polarization interferometry experiments further support a strong interaction between this particle and heparin.

Alpha desynchronization/synchronization during working memory testing is compromised in acute mild traumatic brain injury (mTBI).

Diagnosing and monitoring recovery of patients with mild traumatic brain injury (mTBI) is challenging because of the lack of objective, quantitative measures. Diagnosis is based on description of injuries often not witnessed, subtle neurocognitive symptoms, and neuropsychological testing. Since working memory (WM) is at the center of cognitive functions impaired in mTBI, this study was designed to define objective quantitative electroencephalographic (qEEG) measures of WM processing that may correlate with cognitive changes associated with acute mTBI. First-time mTBI patients and mild peripheral (limb) trauma controls without head injury were recruited from the emergency department. WM was assessed by a continuous performance task (N-back). EEG recordings were obtained during N-back testing on three occasions: within five days, two weeks, and one month after injury. Compared with controls, mTBI patients showed abnormal induced and evoked alpha activity including event-related desynchronization (ERD) and synchronization (ERS). For induced alpha power, TBI patients had excessive frontal ERD on their first and third visit. For evoked alpha, mTBI patients had lower parietal ERD/ERS at the second and third visits. These exploratory qEEG findings offer new and non-invasive candidate measures to characterize the evolution of injury over the first month, with potential to provide much-needed objective measures of brain dysfunction to diagnose and monitor the consequences of mTBI.