Solvent polarity and hydrophobicity of solutes are two sides of the same coin.

The hydrophobicity of solutes measures the intensity of a solute's interaction with aqueous environment. The aqueous environment may change with its composition, leading to changes in its solvent properties largely characterized by polarity. As a result, the relative hydrophobicity of a solute is a function of the solute structure and the properties of the water-based solvent determined by the total composition of the aqueous phase. This aspect is commonly ignored by medicinal chemists even though it is essential for drug distribution between different biological tissues. Partitioning of solutes in aqueous two-phase systems provides the relative hydrophobicity estimates for any water-soluble compounds that can be used to improve predictions of the toxicity and other biological effects of these compounds.

A Possible Path towards Rapid Development of Live-Attenuated SARS-CoV-2 Vaccines: Plunging into the Natural Pool.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic spreading around the world, causing massive distress to the world's economy and affecting healthcare systems worldwide. Although some exposed individuals have no symptoms and most symptomatic infections are not severe, COVID-19 cases span a wide spectrum, ranging from mild to critical and sometimes resulting in life-threatening complications, such as pneumonia, severe respiratory distress and cardiac problems. Currently, there is no curative drug for COVID-19 and vaccines are still under development. We are presenting here a strategy for the fast development of natural live-attenuated SARS-CoV-2 vaccines. Our proposed approach is based on screening for, identifying, analyzing and selecting naturally attenuated yet highly immunogenic SARS-CoV-2 strains, which may lead to a shorter cycle of vaccine development, as well as higher vaccine effectiveness.

Context- and Subgroup-Specific Language Changes in Individuals Who Develop PTSD After Trauma.

Post-traumatic stress disorder (PTSD) is a very common condition with more than 3 million new cases per year in the US alone. The right diagnosis in a timely manner is key to ensuring a prompt treatment that could lead to a full recovery. Unfortunately, avoidance of trauma reminders, social stigma, self-presentation, and self-assessment biases often prevent individuals from seeking timely evaluation, leading to delays in treatment and suboptimal outcomes. Previous studies show that various mental health conditions are associated with distinct patterns of language use. Analyzing language use may also help to avoid response bias in self-reports. In this study, we analyze text data from online forum users, showing that language use differences between PTSD sufferers and controls. In all groups of PTSD sufferers, the usage of singular first-person pronouns was higher and that of plural first-person pronouns was lower than in control groups. However, the analysis of other word categories suggests that subgroups of people with the same mental health disorder (here PTSD) may have salient differences in their language use, particularly in word usage frequencies. Additionally, we show that word usage patterns may vary depending on the type of the text analyzed. Nevertheless, more studies will be needed to increase precision by further examine a variety of text types and different comorbidities. If properly developed, such tools may facilitate earlier PTSD diagnosis, leading to timely support and treatment, which are associated with better outcomes.

Hypothesis: Regulation of neuroplasticity may involve I-motif and G-quadruplex DNA formation modulated by epigenetic mechanisms.

Recent studies demonstrated the existence in vivo of various functional DNA structures that differ from the double helix. The G-quadruplex (G4) and intercalated motif (I-motif or IM) DNA structures are formed as knots where, correspondingly, guanines or cytosines on the same strand of DNA bind to each other. There are grounds to believe that G4 and IM sequences play a significant role in regulating gene expression considering their tendency to be found in or near regulatory sites (such as promoters, enhancers, and telomeres) as well as the correlation between the prevalence of G4 or IM conformations and specific phases of cell cycle. Notably, G4 and IM capable sequences tend to be found on the opposite strands of the same DNA site with at most one of the two structures formed at any given time. The recent evidence that K+, Mg2+ concentrations directly affect IM formation (and likely G4 formation indirectly) lead us to believe that these structures may play a major role in synaptic plasticity of neurons, and, therefore, in a variety of central nervous system (CNS) functions including memory, learning, habitual behaviors, pain perception and others. Furthermore, epigenetic mechanisms, which have an important role in synaptic plasticity and memory formation, were also shown to influence formation and stability of G4s and IMs. Our hypothesis is that non-canonical DNA and RNA structures could be an integral part of neuroplasticity control via gene expression regulation at the level of transcription, translation and splicing. We propose that the regulatory activity of DNA IM and G4 structures is modulated by DNA methylation/demethylation of the IM and/or G4 sequences, which facilitates the switch between canonical and non-canonical conformation. Other neuronal mechanisms interacting with the formation and regulatory activity of non-canonical DNA and RNA structures, particularly G4, IM and triplexes, may involve microRNAs as well as ion and proton fluxes. We are proposing experiments in acute brain slices and in vivo to test our hypothesis. The proposed studies would provide new insights into fundamental neuronal mechanisms in health and disease and potentially open new avenues for treating mental health disorders.

Amelioration of obsessive-compulsive disorder in three mouse models treated with one epigenetic drug: unraveling the underlying mechanism.

Mental health disorders are manifested in families, yet cannot be fully explained by classical Mendelian genetics. Changes in gene expression via epigenetics present a plausible mechanism. Anxiety often leads to avoidant behaviors which upon repetition may become habitual, maladaptive and resistant to extinction as observed in obsessive compulsive disorders (OCD). Psychophysical models of OCD propose that anxiety (amygdala) and habits (dorsolateral striatum, DLS) may be causally linked. The amygdala activates spiny projection neurons in the DLS. Repetitive amygdala terminal stimulation in the DLS elicits long term OCD-like behavior in mice associated with circuitry changes and gene methylation-mediated decrease in the activity of protein phosphatase 1 (PP1). Treatment of OCD-like grooming behavior in Slitrk5, SAPAP3, and laser-stimulated mice with one dose of RG108 (DNA methyltransferase inhibitor), lead to marked symptom improvement lasting for at least one week as well as complete reversal of anomalous changes in circuitry and PP1 gene methylation.