Research Priorities for Autonomous Sensory Meridian Response: An Interdisciplinary Delphi Study.

Autonomous Sensory Meridian Response (ASMR) is a multisensory experience most often associated with feelings of relaxation and altered consciousness, elicited by stimuli which include whispering, repetitive movements, and close personal attention. Since 2015, ASMR research has grown rapidly, spanning disciplines from neuroscience to media studies but lacking a collaborative or interdisciplinary approach. To build a cohesive and connected structure for ASMR research moving forwards, a modified Delphi study was conducted with ASMR experts, practitioners, community members, and researchers from various disciplines.

Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression.

The serotonin pathway has long been proposed as a promising target for pulmonary arterial hypertension (PAH)-a progressive and uncurable disease. We developed a highly specific inhibitor of the serotonin synthesizing enzyme tryptophan hydroxylase 1 (TPH1), TPT-001 (TPHi). In this study, the authors sought to treat severe PAH in the Sugen/hypoxia (SuHx) rat model with the oral TPHi TPT-001.

Design, quality and validation of the EU-OPENSCREEN fragment library poised to a high-throughput screening collection.

The EU-OPENSCREEN (EU-OS) European Research Infrastructure Consortium (ERIC) is a multinational, not-for-profit initiative that integrates high-capacity screening platforms and chemistry groups across Europe to facilitate research in chemical biology and early drug discovery. Over the years, the EU-OS has assembled a high-throughput screening compound collection, the European Chemical Biology Library (ECBL), that contains approximately 100 000 commercially available small molecules and a growing number of thousands of academic compounds crowdsourced through our network of European and non-European chemists. As an extension of the ECBL, here we describe the computational design, quality control and use case screenings of the European Fragment Screening Library (EFSL) composed of 1056 mini and small chemical fragments selected from a substructure analysis of the ECBL.

Experiencing beauty in everyday life.

Beauty surrounds us in many ways every day. In three experience sampling (ESM) studies we investigated frequency, category of eliciting stimuli (natural vs human-made) and, the potential moderating role of several individual difference measures on such everyday experiences of beauty in an ecologically valid manner. Further, we explored the impact of such experiences on valence & arousal.

Autophagy-dependent alternative splicing of ribosomal protein S24 produces a more stable isoform that aids in hypoxic cell survival.

Cells remodel splicing and translation machineries to mount specialized gene expression responses to stress. Here, we show that hypoxic human cells in 2D and 3D culture models increase the relative abundance of a longer mRNA variant of ribosomal protein S24 (RPS24L) compared to a shorter mRNA variant (RPS24S) by favoring the inclusion of a 22 bp cassette exon. Mechanistically, RPS24L and RPS24S are induced and repressed, respectively, by distinct pathways in hypoxia: RPS24L is induced in an autophagy-dependent manner, while RPS24S is reduced by mTORC1 repression in a hypoxia-inducible factor-dependent manner.

Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors.

Tryptophan hydroxylases catalyze the first and rate-limiting step in the biosynthesis of serotonin, a well-known neurotransmitter that plays an important role in multiple physiological functions. A reduction of serotonin levels, especially in the brain, can cause dysregulation leading to depression or insomnia. In contrast, overproduction of peripheral serotonin is associated with symptoms like carcinoid syndrome and pulmonary arterial hypertension.

Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis.

Metastasis is directly linked to poor prognosis of cancer patients and warrants search for effective anti-metastatic drugs. MACC1 is a causal key molecule for metastasis. High MACC1 expression is prognostic for metastasis and poor survival.

Small Molecules Targeting Human UDP-GlcNAc 2-Epimerase.

Uridine diphosphate N-acetylglucosamine 2-epimerase (GNE) is a key enzyme in the sialic acid biosynthesis pathway. Sialic acids are primarily terminal carbohydrates on glycans and play fundamental roles in health and disease. In search of effective GNE inhibitors not based on a carbohydrate scaffold, we performed a high-throughput screening campaign of 68,640 drug-like small molecules against recombinant GNE using a UDP detection assay.

The process of replication target selection in psychology: what to consider?

Increased execution of replication studies contributes to the effort to restore credibility of empirical research. However, a second generation of problems arises: the number of potential replication targets is at a serious mismatch with available resources. Given limited resources, replication target selection should be well-justified, systematic and transparently communicated.

Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.

Microglia are the immune effector cells of the central nervous system (CNS) and react to pathologic events with a complex process including the release of nitric oxide (NO). NO is a free radical, which is toxic for all cells at high concentrations. To target an exaggerated NO release, we tested a library of 16 544 chemical compounds for their effect on lipopolysaccharide (LPS)-induced NO release in cell line and primary neonatal microglia.

Probing Factor Xa Protein-Ligand Interactions: Accurate Free Energy Calculations and Experimental Validations of Two Series of High-Affinity Ligands.

The accurate prediction of protein-ligand binding affinity belongs to one of the central goals in computer-based drug design. Molecular dynamics (MD)-based free energy calculations have become increasingly popular in this respect due to their accuracy and solid theoretical basis. Here, we present a combined study which encompasses experimental and computational studies on two series of factor Xa ligands, which enclose a broad chemical space including large modifications of the central scaffold.

Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors.

Tryptophan hydroxylases catalyze the first and rate-limiting step in the synthesis of serotonin. Serotonin is a key neurotransmitter in the central nervous system and, in the periphery, functions as a local hormone with multiple physiological functions. Studies in genetically altered mouse models have shown that dysregulation of peripheral serotonin levels leads to metabolic, inflammatory, and fibrotic diseases.

Can a Brief Interaction With Online, Digital Art Improve Wellbeing? A Comparative Study of the Impact of Online Art and Culture Presentations on Mood, State-Anxiety, Subjective Wellbeing, and Loneliness.

When experienced in-person, engagement with art has been associated-in a growing body of evidence-with positive outcomes in wellbeing and mental health. This represents an exciting new field for psychology, curation, and health interventions, suggesting a widely-accessible, cost-effective, and non-pharmaceutical means of regulating factors such as mood or anxiety. However, can similar impacts be found with online presentations? If so, this would open up positive outcomes to an even-wider population-a trend accelerating due to the current COVID-19 pandemic.

Does art reduce pain and stress? A registered report protocol of investigating autonomic and endocrine markers of music, visual art, and multimodal aesthetic experience.

The pain- and stress-reducing effects of music are well-known, but the effects of visual art, and the combination of these two, are much less investigated. We aim to (1) investigate the pain- and (2) stress-reducing effects of multimodal (music + visual art) aesthetic experience as we expect this to have stronger effects than a single modal aesthetic experience (music/ visual art), and in an exploratory manner, (3) investigate the underlying mechanisms of aesthetic experience, and the (4) individual differences. In a repeated-measures design (music, visual art, multimodal aesthetic experience, control) participants bring self-selected "movingly beautiful" visual artworks and pieces of music to the lab, where pain and stress are induced by the cold pressor test.

Testing the facsimile accommodation hypothesis.

Research has failed to find evidence for a genuineness effect: the idea that aesthetic experiences are better when looking at real artworks versus reproductions of those artworks. One common explanation for this lack of an effect is the facsimile accommodation hypothesis. This hypothesis states that people can "look past" the limitations of a reproduction, which obscures the effect.

Enhanced Properties of a Benzimidazole Benzylpyrazole Lysine Demethylase Inhibitor: Mechanism-of-Action, Binding Site Analysis, and Activity in Cellular Models of Prostate Cancer.

Jumonji domain-containing lysine demethylase (KDM) enzymes are encoded by genes of the KDM superfamily. Activities of the KDM4 subfamily promote aggressive phenotypes associated with prostate cancer (PCa). Previously, we discovered a benzimidazole pyrazole molecule that inhibited KDM4 isoforms with properties tractable for development.

Topical inflammasome inhibition with disulfiram prevents irritant contact dermatitis.

Background: The pathogenesis of contact dermatitis, a common inflammatory skin disease with limited treatment options, is held to be driven by inflammasome activation induced by allergens and irritants. We here aim to identify inflammasome-targeting treatment strategies for irritant contact dermatitis.

Methods: A high content screen with 41,184 small molecules was performed using fluorescent Apoptosis associated speck-like protein containing a CARD (ASC) speck formation as a readout for inflammasome activation.

The Display Makes a Difference: A Mobile Eye Tracking Study on the Perception of Art Before and After a Museum's Rearrangement.

There is increasing awareness that the perception of art is affected by the way it is presented. In 2018, the Austrian Gallery Belvedere redisplayed its permanent collection. Our multidisciplinary team seized this opportunity to investigate the viewing behavior of specific artworks both before and after the museum's rearrangement.

Dispersion matters: Diagnostics and control data computer simulation in Concealed Information Test studies.

Binary classification has numerous applications. For one, lie detection methods typically aim to classify each tested person either as "liar" or as "truthteller" based on the given test results. To infer practical implications, as well as to compare different methods, it is essential to assess the diagnostic efficiency, such as demonstrating the number of correctly classified persons.

NMR quality control of fragment libraries for screening.

Fragment-based screening has evolved as a remarkable approach within the drug discovery process both in the industry and academia. Fragment screening has become a more structure-based approach to inhibitor development, but also towards development of pathway-specific clinical probes. However, it is often witnessed that the availability, immediate and long-term, of a high quality fragment-screening library is still beyond the reach of most academic laboratories.

Warm, lively, rough? Assessing agreement on aesthetic effects of artworks.

The idea that simple visual elements such as colors and lines have specific, universal associations-for example red being warm-appears rather intuitive. Such associations have formed a basis for the description of artworks since the 18th century and are still fundamental to discourses on art today. Art historians might describe a painting where red is dominant as "warm," "aggressive," or "lively," with the tacit assumption that beholders would universally associate the works' certain key forms with specific qualities, or "aesthetic effects".