NMR structures and magnetic force spectroscopy studies of small molecules binding to models of an RNA CAG repeat expansion.

RNA repeat expansions fold into stable structures and cause microsatellite diseases such as Huntington's disease (HD), myotonic dystrophy type 1 (DM1), and spinocerebellar ataxias (SCAs). The trinucleotide expansion of r(CAG), or r(CAG), causes both HD and SCA3, and the RNA's toxicity has been traced to its translation into polyglutamine (polyQ; HD) as well as aberrant pre-mRNA alternative splicing (SCA3 and HD). Previously, a small molecule, , was discovered that binds to r(CAG) and rescues aberrant pre-mRNA splicing in patient-derived fibroblasts by freeing proteins bound to the repeats.

NMR structures of small molecules bound to a model of a CUG RNA repeat expansion.

Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to these structured RNAs. Both Huntington's disease-like 2 (HDL2) and myotonic dystrophy type 1 (DM1) are caused by a r(CUG) repeat expansion, or r(CUG).

NMR structures of small molecules bound to a model of an RNA CUG repeat expansion.

Trinucleotide repeat expansions fold into long, stable hairpins and cause a variety of incurable RNA gain-of-function diseases such as Huntington's disease, the myotonic dystrophies, and spinocerebellar ataxias. One approach for treating these diseases is to bind small molecules to the structured RNAs. Both Huntington's disease-like 2 (HDL2) and myotonic dystrophy type 1 (DM1) are caused by a r(CUG) repeat expansion, or r(CUG).

Possible new phase transition in the 3D Ising model associated with boundary percolation.

In the ordered phase of the 3D Ising model, minority spin clusters are surrounded by a boundary of dual plaquettes. As the temperature is raised, these spin clusters become more numerous, and it is found that eventually their boundaries undergo a percolation transition when about 13% of spins are minority. Boundary percolation differs from the more commonly studied site and link percolation, although it is related to an unusual type of site percolation that includes next to nearest neighbor relationships.

The Psychological Science Accelerator's COVID-19 rapid-response dataset.

In response to the COVID-19 pandemic, the Psychological Science Accelerator coordinated three large-scale psychological studies to examine the effects of loss-gain framing, cognitive reappraisals, and autonomy framing manipulations on behavioral intentions and affective measures. The data collected (April to October 2020) included specific measures for each experimental study, a general questionnaire examining health prevention behaviors and COVID-19 experience, geographical and cultural context characterization, and demographic information for each participant. Each participant started the study with the same general questions and then was randomized to complete either one longer experiment or two shorter experiments.

Bruce G. Klonsky (1950-2022).

This article memorializes Bruce G. Klonsky (1950-2022), a devoted State University of New York at Fredonia (SUNY) educator and researcher. After joining SUNY Fredonia Psychology Department in 1979, he taught a wide range of psychology courses (15+), supervised hundreds of internship students, and was a creative research mentor for many undergraduates.

Neutrophils and neutrophil extracellular traps in cancer: promising targets for engineered nanomaterials.

Neutrophils are the most abundant white blood cells in circulation and constitute up to 60% of circulating leukocytes. Neutrophils play a significant role in host defense against pathogens through various mechanisms, including phagocytosis, production of antimicrobial proteins, and formation of neutrophil extracellular traps (NETs). Recently, the role of neutrophils and NETs in cancer has generated significant interest, as accumulating evidence suggests that neutrophils and NETs contribute to cancer progression and are associated with adverse patient outcomes.

Neutrophil Extracellular Traps, Sepsis and COVID-19 - A Tripod Stand.

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the current coronavirus disease 2019 (COVID-19) pandemic. Majority of COVID-19 patients have mild disease but about 20% of COVID-19 patients progress to severe disease. These patients end up in the intensive care unit (ICU) with clinical manifestations of acute respiratory distress syndrome (ARDS) and sepsis.

TNKPVI, a Putative Bioaccessible Pharmacophore of Anti-Inflammatory Potato Patatin-Derived Decapeptide DIKTNKPVIF.

Potato protein-derived decapeptide DIKTNKPVIF exerted anti-inflammatory activity in animal models when delivered via intragastric gavage and intraperitoneal injection. However, DIKTNKPVIF is susceptible to hydrolysis in the digestive tract, which will decrease its bioaccessibility and possibly bioactivity. In this study, the anti-inflammatory activity of fragments generated from in silico gastrointestinal enzymatic hydrolysis of DIKTNKPVIF was investigated using the human monocytic (THP-1) cell line.

Situational factors shape moral judgements in the trolley dilemma in Eastern, Southern and Western countries in a culturally diverse sample.

The study of moral judgements often centres on moral dilemmas in which options consistent with deontological perspectives (that is, emphasizing rules, individual rights and duties) are in conflict with options consistent with utilitarian judgements (that is, following the greater good based on consequences). Greene et al. (2009) showed that psychological and situational factors (for example, the intent of the agent or the presence of physical contact between the agent and the victim) can play an important role in moral dilemma judgements (for example, the trolley problem).

Keep Calm and Carry on with Extra Centrosomes.

Aberrations in the centrosome number and structure can readily be detected at all stages of tumor progression and are considered hallmarks of cancer. Centrosome anomalies are closely linked to chromosome instability and, therefore, are proposed to be one of the driving events of tumor formation and progression. This concept, first posited by Boveri over 100 years ago, has been an area of interest to cancer researchers.

An Exploratory Investigation of Parental Incarceration, Emotional Independence, and Adult Children's Criminal Activity.

Although research suggests that parental incarceration is associated with intergenerational continuity in crime, the mechanisms underlying this association remain unclear. Using multi-population structural equation modeling and data from the Toledo Adolescent Relationships Study ( = 1207), the current study explored specific experiences associated with labeling as well as internalizing labels, including experiencing corporal punishment during childhood, criminal arrests during adolescence, and identifying as a troublemaker/partier in young adulthood (measured with reflected appraisals), as potential mechanisms linking parental incarceration and young adults' offending. We assessed whether this association differed by young adults' level of emotional independence, that is, freedom from the need for parental approval.

Race/Ethnicity, Perceived Skin Color, and the Likelihood of Adult Arrest.

Research has long-documented racial/ethnic disparities in criminal justice outcomes. However, despite race/ethnicity being a multidimensional social construct, prior research largely relies on self-identification measures, thereby disregarding research on skin tone stratification within-racial/ethnic groups. The current study extends beyond this by examining the relationship between race/ethnicity and arrest employing both self-identified race/ethnicity and perceived skin color.

Spatial Distribution of Microplastics in Surficial Benthic Sediment of Lake Michigan and Lake Erie.

The spatial distribution, concentration, particle size, and polymer compositions of microplastics in Lake Michigan and Lake Erie sediment were investigated. Fibers/lines were the most abundant of the five particle types characterized. Microplastic particles were observed in all samples with mean concentrations for particles greater than 0.

Design, Optimization, and Study of Small Molecules That Target Tau Pre-mRNA and Affect Splicing.

Approximately 95% of human genes are alternatively spliced, and aberrant splicing events can cause disease. One pre-mRNA that is alternatively spliced and linked to neurodegenerative diseases is tau (microtubule-associated protein tau), which can cause frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) and can contribute to Alzheimer's disease. Here, we describe the design of structure-specific lead small molecules that directly target tau pre-mRNA from sequence.

The Impact of Invisible Illness and Invisible Disability on Music Therapy Practica Students.

A variety of factors affect the success of music therapy students in practica. Many music therapy students may have invisible illnesses or invisible disabilities (II/ID) that affect their work. II/ID have physical or psychological effects but are not apparent to an observer.

Confounding Bias in the Relationship Between Problem Gambling and Crime.

Although the relationship between problem gambling and criminal behavior has been widely researched, concerns over the causal nature of this association remain. Some argue that problem gambling does not lead to crime; instead, the same background characteristics that predict problem gambling also predict criminal behavior. Yet, studies suggestive of a spurious association often rely on small, non-random, and cross-sectional samples; thus, the extent to which the findings are generalizable to the broader population is unknown.

Identifying as a Troublemaker/Partier: The Influence of Parental Incarceration and Emotional Independence.

Objectives: Researchers have found that experiencing parental incarceration has long-term consequences for children, such as involvement in crime. However, few studies have examined how parental incarceration influences identity endorsement. Given that self-identities influence behavior, including criminal activity, understanding precursors of self-identities is important.

Shifting the gaze of the physician from the body to the body in a place: A qualitative analysis of a community-based photovoice approach to teaching place-health concepts to medical students.

Medical practitioners, trained to isolate health within and upon the body of the individual, are now challenged to negotiate research and population health theories that link health status to geographic location as evidence suggests a connection between place and health. This paper builds an integrated place-health model and structural competency analytical framework with nine domains and four levels of proficiency that is utilized to assess a community-based photovoice project's ability to shift the practice of medicine by medical students from the surface of the body to the body within a place. Analysis of the medical student's photovoice data demonstrated that the students achieved structural competency level 1 proficiency and came to understand how health might be connected to place represented by six of the nine domains of the structural competency framework.

Medical disorder, harm, and damage.

Jerome Wakefield's harmful dysfunction analysis (HDA) of medical disorder is an influential hybrid of naturalist and normative theories. In order to conclude that a condition is a disorder, according to the HDA, one must determine both that it results from a failure of a physical or psychological mechanism to perform its natural function and that it is harmful. In a recent issue of this journal, I argued that the HDA entails implausible judgments about which disorders there are and how they are individuated.

Mixing it up: the biological significance of hybrid skeletal muscle fibers.

Skeletal muscle fibers are classified according to the myosin heavy chain (MHC) isoforms and other myofibrillar proteins expressed within these cells. In addition to 'pure' fibers expressing single MHC isoforms, many fibers are 'hybrids' that co-express two or more different isoforms of MHC or other myofibrillar proteins. Although hybrid fibers have been recognized by muscle biologists for more than three decades, uncertainty persists about their prevalence in normal muscles, their role in fiber-type transitions, and what they might tell us about fiber-type regulation at the cellular and molecular levels.

Vertical Distribution of Microplastics in the Water Column and Surficial Sediment from the Milwaukee River Basin to Lake Michigan.

Microplastic contamination was studied along a freshwater continuum from inland streams to the Milwaukee River estuary to Lake Michigan and vertically from the water surface, water subsurface, and sediment. Microplastics were detected in all 96 water samples and 9 sediment samples collected. Results indicated a gradient of polymer presence with depth: low-density particles decreased from the water surface to the subsurface to sediment, and high-density particles had the opposite result.

Use of Prescribed Psychotropics during Pregnancy: A Systematic Review of Pregnancy, Neonatal, and Childhood Outcomes.

This paper reviews the findings from preclinical animal and human clinical research investigating maternal/fetal, neonatal, and child neurodevelopmental outcomes following prenatal exposure to psychotropic drugs. Evidence for the risks associated with prenatal exposure was examined, including teratogenicity, neurodevelopmental effects, neonatal toxicity, and long-term neurobehavioral consequences (i.e.

Transitional Hybrid Skeletal Muscle Fibers in Rat Soleus Development.

Skeletal muscles comprise hundreds of individual muscle fibers, with each possessing specialized contractile properties. Skeletal muscles are recognized as being highly plastic, meaning that the physiological properties of single muscle fibers can change with appropriate use. During fiber type transitions, one myosin heavy chain isoform is exchanged for another and over time the fundamental nature of the fiber adapts to become a different fiber type.