A unique dermatopathology incident arose after administration of the mRNA-1273 SARS-CoV-2 (Moderna) vaccine. Specifically, a transient purpuric interface dermatitis occurred 5 days post-second vaccine with the presentation of erythematous papules with erythema multiforme-type findings. A patient developed purpuric interface dermatitis with micro-vesiculation post-vaccination which ultimately resolved without sequelae.

Post-traumatic epilepsy is the architype of acquired epilepsies, wherein a brain insult initiates an epileptogenic process culminating in an unprovoked seizure after weeks, months or years. Identifying biomarkers of such process is a prerequisite for developing and implementing targeted therapies aimed at preventing the development of epilepsy. Currently, there are no validated electrophysiological biomarkers of post-traumatic epileptogenesis. Experimental EEG studies using the lateral fluid percussion injury model have identified three candidate biomarkers of post-traumatic epileptogenesis: pathological high-frequency oscillations (HFOs, 80-300 Hz); repetitive HFOs and spikes (rHFOSs); and reduction in sleep spindle duration and dominant frequency at the transition from stage III to rapid eye movement sleep. EEG studies in humans have yielded conflicting data; recent evidence suggests that epileptiform abnormalities detected acutely after traumatic brain injury carry a significantly increased risk of subsequent epilepsy. Well-designed studies are required to validate these promising findings, and ultimately establish whether there are post-traumatic electrophysiological features which can guide the development of antiepileptogenic therapies.

Bicontinuous jammed emulsions (or bijels) are tortuous, interconnected structures of two immiscible liquids, kinetically trapped by colloidal particles that are irreversibly bound to the oil-water interface. A wealth of applications has been proposed for bijels in catalysis, energy storage and molecular encapsulation, but large domain sizes (on the order of 5 µm or larger) and difficulty in fabrication pose major barriers to their use. Here, we show that bijels with sub-micrometre domains can be formed via homogenization, rather than spinodal decomposition. We achieve this by using nanoparticle surfactants: polymers and nanoparticles of complementary functionality (for example, ion-pairing) that bind to one another at the oil-water interface. This allows the stabilization of the bijel far from the demixing point of the liquids, with interfacial tensions on the order of 20 mN m^-1. Furthermore, our strategy is extremely versatile, as solvent, nanoparticle and ligand can all be varied.

Traumatic brain injury (TBI) is major neurological burden globally, and effective treatments are urgently needed. TBI is characterized by a reduction in energy metabolism and synaptic function that seems a primary cause of neuronal dysfunction. R13, a small drug and BDNF mimetic showed promising results in improving spatial memory and anxiety-like behavior after TBI. Additionally, R13 was found to counteract reductions in molecules associated with BDNF signaling (p-TrkB, p-PI3K, p-AKT), synaptic plasticity (GluR2, PSD95, Synapsin I) as well as bioenergetic components such as mitophagy (SOD, PGC-1α, PINK1, Parkin, BNIP3, and LC3) and real-time mitochondrial respiratory capacity. Behavioral and molecular changes were accompanied by adaptations in functional connectivity assessed using MRI. Results highlight the potential of R13 as a therapeutic agent for TBI and provide valuable insights into the molecular and functional changes associated with this condition.

We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning of molecules, and Watson-Crick selectivity, such that, among all solutions of adenosine, cytosine, guanine, and thymine NTPs and their binary mixtures, duplex columnar ordering is most stable in the A-T and C-G combinations.

Polyoxometalates (POMs) using {Mo₇₂V₃₀} as an example, dissolved in water, can interact with amine-terminated polydimethylsiloxane (PDMS-NH₂) dissolved in toluene at the water/toluene interface to form POM-surfactants that significantly lower the interfacial tension and can be used to stabilize liquids via interfacial elasticity. The jamming of the POM-surfactants at the water/oil interface with consequent wrinkling occurs with a decrease in the interfacial area. The packing density of the POM-surfactants at the interface can be tuned by varying the strength of screening with the addition of cations with differing hydrated radii.

Inside the virions of α-herpesviruses, tegument protein pUL25 anchors the tegument to capsid vertices through direct interactions with tegument proteins pUL17 and pUL36. In addition to promoting virion assembly, both pUL25 and pUL36 are critical for intracellular microtubule-dependent capsid transport. Despite these essential roles during infection, the stoichiometry and precise organization of pUL25 and pUL36 on the capsid surface remain controversial due to the insufficient resolution of existing reconstructions from cryo-electron microscopy (cryoEM). Here, we report a three-dimensional (3D) icosahedral reconstruction of pseudorabies virus (PRV), a varicellovirus of the α-herpesvirinae subfamily, obtained by electron-counting cryoEM at 4.9 Å resolution. Our reconstruction resolves a dimer of pUL25 forming a capsid-associated tegument complex with pUL36 and pUL17 through a coiled coil helix bundle, thus correcting previous misinterpretations. A comparison between reconstructions of PRV and the γ-herpesvirus Kaposi's sarcoma-associated herpesvirus (KSHV) reinforces their similar architectures and establishes important subfamily differences in the capsid-tegument interface.

Background

DNA aptamers represent a novel strategy in anti-cancer medicine. AS1411, a DNA aptamer targeting nucleolin (a protein which is overexpressed in many tumor types), was evaluated in patients with metastatic, clear-cell, renal cell carcinoma (RCC) who had failed treatment with ≥1 prior tyrosine kinase inhibitor.

Methods

In this phase II, single-arm study, AS1411 was administered at 40 mg/kg/day by continuous intravenous infusion on days 1-4 of a 28-day cycle, for two cycles. Primary endpoint was overall response rate; progression-free survival (PFS) and safety were secondary endpoints.

Results

35 patients were enrolled and treated. One patient (2.9 %) had a response to treatment. The response was dramatic (84 % reduction in tumor burden by RECIST 1.0 criteria) and durable (patient remains free of progression 2 years after completing therapy). Whole exome sequencing of this patient's tumor revealed missense mutations in the mTOR and FGFR2 genes which is of interest because nucleolin is known to upregulate mTOR pathway activity by enhancing AKT1 mRNA translation. No other responses were seen. Thirty-four percent of patients had an AS1411-related adverse event, all of which were mild or moderate.

Conclusions

AS1411 appears to have minimal activity in unselected patients with metastatic RCC. However, rare, dramatic and durable responses can be observed and toxicity is low. One patient in this study had an excellent response and was found to have FGFR2 and mTOR mutations which will be of interest in future efforts to discover and validate predictive biomarkers of response to nucleolin targeted compounds. DNA aptamers represent a novel way to target cancer cells at a molecular level and continue to be developed with a view to improving treatment and imaging in cancer medicine.