Neighborhood Greenspace, Extreme Heat Exposure, and Sleep Quality over Time among a Nationally Representative Sample of American Children.

Children's sleep is essential for healthy development, yet over a third of children in the United States experience inadequate sleep. Environmental factors can influence sleep: greenspace exposure can promote better sleep, while heat exposure can disrupt sleep. As global climate change raises nighttime and daytime temperatures, greenspace may mitigate the negative effects of heat stress on sleep.

Detecting Patient Position Using Bed-Reaction Forces for Pressure Injury Prevention and Management.

A key best practice to prevent and treat pressure injuries (PIs) is to ensure at-risk individuals are repositioned regularly. Our team designed a non-contact position detection system that predicts an individual's position in bed using data from load cells under the bed legs. The system was originally designed to predict the individual's position as left-side lying, right-side lying, or supine.

Integrative Molecular Structure Elucidation and Construction of an Extended Metabolic Pathway Associated with an Ancient Innate Immune Response in COVID-19 Patients.

We present compelling evidence for the existence of an extended innate viperin-dependent pathway, which provides crucial evidence for an adaptive response to viral agents, such as SARS-CoV-2. We show the in vivo biosynthesis of a family of novel endogenous cytosine metabolites with potential antiviral activities. Two-dimensional nuclear magnetic resonance (NMR) spectroscopy revealed a characteristic spin-system motif, indicating the presence of an extended panel of urinary metabolites during the acute viral replication phase.

Chemoenzymatic Synthesis of 3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP).

3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin during the early stages of the innate immune response. ddhCTP has been shown to act as a chain terminator of flavivirus RNA-dependent RNA polymerases. To date, synthesis of ddhCTP requires complicated synthetic protocols or isolation of the enzyme viperin to catalyze the production of ddhCTP from CTP.

Galidesivir Triphosphate Promotes Stalling of Dengue-2 Virus Polymerase Immediately Prior to Incorporation.

Millions of people are infected by the dengue and Zika viruses each year, resulting in significant morbidity and mortality. Galidesivir is an adenosine nucleoside analog that can attenuate flavivirus replication in cell-based assays and animal models of infection. Galidesivir is converted to the triphosphorylated form by host kinases and subsequently incorporated into viral RNA by viral RNA polymerases.

Designing learning environments for promoting young people's constructive coping with climate change.

This chapter first summarizes how the consequences of global climate change (GCC) can harm young people's well-being through physical health impacts and awareness of GCC. We then outline how youth may cope with GCC by denying the problem, distancing themselves from it, or taking individual actions. However, the coping strategy shown to have the best mental well-being outcomes relates to collective actions and agency.

Cumulative Neurotoxicological Air Pollution Exposure Is Associated with Lower Reading Improvement and Diminished Benefits of Literacy Interventions for Urban Elementary Students of Color.

The cognitive and behavioral deficits associated with air pollution exposure may have far-reaching negative effects on children's scholastic achievement. Moreover, air pollution may be conditioning the success of educational investments that support students who face greatest levels of societal adversity. This study examined the direct main effects of cumulative neurotoxicological exposure on annual reading improvement.

Phosphoinositide and redox dysregulation by the anticancer methylthioadenosine phosphorylase transition state inhibitor.

Methylthio-DADMe-immucillin-A (MTDIA) is an 86 picomolar inhibitor of 5'-methylthioadenosine phosphorylase (MTAP) with potent and specific anti-cancer efficacy. MTAP salvages S-adenosylmethionine (SAM) from 5'-methylthioadenosine (MTA), a toxic metabolite produced during polyamine biosynthesis. Changes in MTAP expression are implicated in cancer growth and development, making MTAP an appealing target for anti-cancer therapeutics.

An Isomer of Galidesivir That Potently Inhibits Influenza Viruses and Members of the Order.

We report for the first time the antiviral activities of two (antiviral imino--nucleosides) and , structurally related to galidesivir (Immucillin A, BCX4430). An containing the 4-aminopyrrolo[2,1-][1,2,4-triazine] nucleobase found in remdesivir exhibited submicromolar inhibition of multiple strains of influenza A and B viruses, as well as members of the order. We also report the first syntheses of ProTide prodrugs of monophosphates, which unexpectedly displayed poorer viral inhibition than their parent nucleosides .

Pessimistic cognitive biases mediate socioeconomic status and children's mental health problems.

Low socioeconomic status (SES) is associated with higher rates of emotional disorders in childhood and beyond. Here we assessed one possible contributor to this disparity, a cognitive bias in the interpretation of negative events, in a group of 341 9-year-olds (49% female, 94% White) ranging widely in SES. This cognitive bias, known as pessimism in the attributional style literature, is the tendency to interpret negative events as persistent (Stable) and pervasive (Global).

Persistence on challenging tasks mediates the relationship between childhood poverty and mental health problems.

Childhood disadvantage is associated with psychological distress throughout the lifespan. Poor children are alleged to give up more often than their more privileged peers when facing challenges. Yet little research has examined the role of task persistence in poverty and mental health.

Measuring Repositioning in Home Care for Pressure Injury Prevention and Management.

Despite the widespread agreement on the need for the regular repositioning of at-risk individuals for pressure injury prevention and management, adherence to repositioning schedules remains poor in the clinical environment. The situation in the home environment is likely even worse. Our team has developed a non-contact system that can determine an individual's position in bed (left-side lying, supine, or right-side lying) using data from a set of inexpensive load cells placed under the bed.

Cost of resilience: Childhood poverty, mental health, and chronic physiological stress.

Childhood poverty is associated with elevated internalizing symptoms. Nevertheless, some children exposed to poverty evince remarkable resilience, demonstrating lower than expected levels of psychological distress. However, recent work suggests that coping with adversity can lead to undesirable physical health consequences.

Viperin triggers ribosome collision-dependent translation inhibition to restrict viral replication.

Innate immune responses induce hundreds of interferon-stimulated genes (ISGs). Viperin, a member of the radical S-adenosyl methionine (SAM) superfamily of enzymes, is the product of one such ISG that restricts the replication of a broad spectrum of viruses. Here, we report a previously unknown antiviral mechanism in which viperin activates a ribosome collision-dependent pathway that inhibits both cellular and viral RNA translation.

Discovery of AL-GDa62 as a Potential Synthetic Lethal Lead for the Treatment of Gastric Cancer.

Diffuse gastric cancer and lobular breast cancer are aggressive malignancies that are frequently associated with inactivating mutations in the tumor suppressor gene Synthetic lethal (SL) vulnerabilities arising from dysfunction represent attractive targets for drug development. Recently, SLEC-11 () emerged as a SL lead in E-cadherin-deficient cells. Here, we describe our efforts to optimize .

Neural Responses During Emotion Transitions and Emotion Regulation.

Why are some people more susceptible to interference from previous emotional stimuli? Neural mechanisms underlying emotion regulation are typically studied with one-off positive or negative stimuli. Less is known about how they operate during dynamic emotional experiences, which more closely resemble how emotions occur in real life. Therefore, we investigated the interaction among temporal context, stimulus content, and regulatory strategy.

Chemical Synthesis of the Antiviral Nucleotide Analogue ddhCTP.

3'-Deoxy-3',4'-didehydro-cytidine triphosphate (ddhCTP) is a novel antiviral molecule produced by the enzyme viperin as part of the innate immune response. ddhCTP has been shown to act as an obligate chain terminator of flavivirus and SARS-CoV-2 RNA-dependent RNA polymerases; however, further biophysical studies have been precluded by limited access to this promising antiviral. Herein, we report a robust and scalable synthesis of ddhCTP as well as the mono- and diphosphates ddhCMP and ddhCDP, respectively.

A single point mutation converts a glutaryl-7-aminocephalosporanic acid acylase into an N-acyl-homoserine lactone acylase.

Objective: To change the specificity of a glutaryl-7-aminocephalosporanic acid acylase (GCA) towards N-acyl homoserine lactones (AHLs; quorum sensing signalling molecules) by site-directed mutagenesis.

Results: Seven residues were identified by analysis of existing crystal structures as potential determinants of substrate specificity. Site-saturation mutagenesis libraries were created for each of the seven selected positions.

Childhood poverty and psychological well-being: The mediating role of cumulative risk exposure.

The current study assessed whether the proportion of childhood (age 0-9 years) in poverty altered the developmental trajectories (ages 9-24) of multimethodological indicators of psychological well-being. In addition, we tested whether exposure to cumulative risk over time mediated the association between poverty exposure and psychological well-being. Measures of psychological well-being included internalizing and externalizing symptoms, a behavioral index of learned helplessness (task persistence), and chronic physiological stress (allostatic load).