A High-throughput Response to the SARS-CoV-2 Pandemic.

Four years after the beginning of the COVID-19 pandemic, it is important to reflect on the events that have occurred during that time and the knowledge that has been gained. The response to the pandemic was rapid and highly resourced; it was also built upon a foundation of decades of federally funded basic and applied research. Laboratories in government, pharmaceutical, academic, and non-profit institutions all played roles in advancing pre-2020 discoveries to produce clinical treatments. This perspective provides a summary of how the development of high-throughput screening methods in a biosafety level 3 (BSL-3) environment at Southern Research Institute (SR) contributed to pandemic response efforts. The challenges encountered are described, including those of a technical nature as well as those of working under the pressures of an unpredictable virus and pandemic.

High-Throughput cell-based immunofluorescence assays against influenza.

A rapid drug discovery response to influenza outbreaks with the potential to reach pandemic status could help minimize the virus's impact by reducing the time to identify anti-influenza drugs. Although several anti-influenza strategies have been considered in the search for new drugs, only a few therapeutic agents are approved for clinical use. The cytopathic effect induced by the influenza virus in Madin Darby canine kidney (MDCK) cells has been widely used for high-throughput anti-influenza drug screening, but the fact that the MDCK cells are not human cells constitutes a disadvantage when searching for new therapeutic agents for human use. We have developed a highly sensitive cell-based imaging assay for the identification of inhibitors of influenza A and B virus that is high-throughput compatible using the A549 human cell line. The assay has also been optimized for the assessment of the neutralizing effect of anti-influenza antibodies in the absence of trypsin, which allows testing of purified antibodies and serum samples. This assay platform can be applied to full high-throughput screening campaigns or later stages requiring quantitative potency determinations for structure-activity relationships.

Examining the social in the prosocial: Episode-level features of social interactions and kind acts predict social connection and well-being.

Experiments prompting people to engage in more prosocial behavior (e.g., acts of kindness) or simple social interactions (e.g., acting extraverted) have both shown promise in boosting well-being. However, little is known about how much the impact on well-being depends on the type of interpersonal interaction (i.e., social vs. prosocial) or on other proximal features (e.g., whether the interaction takes place online vs. in-person, the closeness of the relationship, or amount of social connection associated with a given interaction). We randomly assigned a sample of full-time employees recruited via a special employed mTurk sample (N = 754) to perform weekly acts of kindness online versus in-person, to engage in weekly social interactions online versus in-person, or to list their daily activities (control) over the course of 4 weeks. First, on average, all conditions reported improvements in well-being (i.e., increases in positive affect and life satisfaction, decreases in negative affect) across the 4-week intervention period. Second, relative to controls, the four experimental groups reported increases in general social connectedness over time. Finally, according to auxiliary analyses collapsed across the experimental condition, closer relationship with target and non-digital medium of delivery predicted episode-level social connection, which, in turn, was associated with general social connectedness and positive affect. We conclude that the "who" and the "how" of a behavior (i.e., its target, its delivery method, and the feelings of social connection generated) are important for well-being, but not the "what" (i.e., whether the behavior is social or prosocial). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The CANDOR corpus: Insights from a large multimodal dataset of naturalistic conversation.

People spend a substantial portion of their lives engaged in conversation, and yet, our scientific understanding of conversation is still in its infancy. Here, we introduce a large, novel, and multimodal corpus of 1656 conversations recorded in spoken English. This 7+ million word, 850-hour corpus totals more than 1 terabyte of audio, video, and transcripts, with moment-to-moment measures of vocal, facial, and semantic expression, together with an extensive survey of speakers' postconversation reflections. By taking advantage of the considerable scope of the corpus, we explore many examples of how this large-scale public dataset may catalyze future research, particularly across disciplinary boundaries, as scholars from a variety of fields appear increasingly interested in the study of conversation.

The P2X4 Receptor: Cellular and Molecular Characteristics of a Promising Neuroinflammatory Target.

The adenosine 5'-triphosphate-gated P2X4 receptor channel is a promising target in neuroinflammatory disorders, but the ability to effectively target these receptors in models of neuroinflammation has presented a constant challenge. As such, the exact role of P2X4 receptors and their cell signalling mechanisms in human physiology and pathophysiology still requires further elucidation. To this end, research into the molecular mechanisms of P2X4 receptor activation, modulation, and inhibition has continued to gain momentum in an attempt to further describe the role of P2X4 receptors in neuroinflammation and other disease settings. Here we provide an overview of the current understanding of the P2X4 receptor, including its expression and function in cells involved in neuroinflammatory signalling. We discuss the pharmacology of P2X4 receptors and provide an overview of P2X4-targeting molecules, including agonists, positive allosteric modulators, and antagonists. Finally, we discuss the use of P2X4 receptor modulators and antagonists in models of neuroinflammatory cell signalling and disease.

Outcasts and saboteurs: Intervention strategies to reduce the negative effects of social exclusion on team outcomes.

The experience of social exclusion in the workplace adversely impacts employees' well-being, job satisfaction, and productivity, and no one quite knows what to do about it. In this report, we describe the development and testing of three ostracism interventions, designed to help people cope with the negative effects of being excluded by one's team. Across five studies, participants were assigned to a virtual ball toss game where they were either included or excluded by their teammates. Afterwards, they were given a task where they could earn money for themselves, for their entire team, or for an unrelated group (charity). Excluded participants worked less hard for their teams (even when this meant sacrificing their own earnings). This sabotage effect was specific, meaning that excluded individuals worked less hard on behalf of their teams, but not when they worked for themselves or for charity. We devised three intervention strategies-perspective, mentorship, and empowerment-to combat the negative effects of ostracism on people's willingness to work for their teams. These interventions were successful; each increased people's persistence in a team-based reward task, and in some cases, even raised the outcomes of excluded teammates to levels observed in included teammates. The effectiveness of these interventions also replicated successfully, using preregistered hypotheses, methods, and analyses. These studies add novel insights to a variety of fields that have examined the consequences of social exclusion, including social psychology, organizational behavior, and management science.

P2Y2 and P2X4 Receptors Mediate Ca2+ Mobilization in DH82 Canine Macrophage Cells.

Purinergic receptors of the P2 subclass are commonly found in human and rodent macrophages where they can be activated by adenosine 5'-triphosphate (ATP) or uridine 5'-triphosphate (UTP) to mediate Ca2+ mobilization, resulting in downstream signalling to promote inflammation and pain. However, little is understood regarding these receptors in canine macrophages. To establish a macrophage model of canine P2 receptor signalling, the expression of these receptors in the DH82 canine macrophage cell line was determined by reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemistry. P2 receptor function in DH82 cells was pharmacologically characterised using nucleotide-induced measurements of Fura-2 AM-bound intracellular Ca2+. RT-PCR revealed predominant expression of P2X4 receptors, while immunocytochemistry confirmed predominant expression of P2Y2 receptors, with low levels of P2X4 receptor expression. ATP and UTP induced robust Ca2+ responses in the absence or presence of extracellular Ca2+. ATP-induced responses were only partially inhibited by the P2X4 receptor antagonists, 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), paroxetine and 5-BDBD, but were strongly potentiated by ivermectin. UTP-induced responses were near completely inhibited by the P2Y2 receptor antagonists, suramin and AR-C118925. P2Y2 receptor-mediated Ca2+ mobilization was inhibited by U-73122 and 2-aminoethoxydiphenyl borate (2-APB), indicating P2Y2 receptor coupling to the phospholipase C and inositol triphosphate signal transduction pathway. Together this data demonstrates, for the first time, the expression of functional P2 receptors in DH82 canine macrophage cells and identifies a potential cell model for studying macrophage-mediated purinergic signalling in inflammation and pain in dogs.

Forecasting the onset and course of mental illness with Twitter data.

We developed computational models to predict the emergence of depression and Post-Traumatic Stress Disorder in Twitter users. Twitter data and details of depression history were collected from 204 individuals (105 depressed, 99 healthy). We extracted predictive features measuring affect, linguistic style, and context from participant tweets (N = 279,951) and built models using these features with supervised learning algorithms. Resulting models successfully discriminated between depressed and healthy content, and compared favorably to general practitioners' average success rates in diagnosing depression, albeit in a separate population. Results held even when the analysis was restricted to content posted before first depression diagnosis. State-space temporal analysis suggests that onset of depression may be detectable from Twitter data several months prior to diagnosis. Predictive results were replicated with a separate sample of individuals diagnosed with PTSD (Nusers = 174, Ntweets = 243,775). A state-space time series model revealed indicators of PTSD almost immediately post-trauma, often many months prior to clinical diagnosis. These methods suggest a data-driven, predictive approach for early screening and detection of mental illness.

Blood sugar level follows perceived time rather than actual time in people with type 2 diabetes.

The current study investigates whether perceived time has an effect on blood glucose level in people with type 2 diabetes. The hypothesis is that perceived time will have a greater influence over blood glucose level than actual time. Changes in blood glucose levels were measured in 46 participants with diabetes while they completed simple tasks during a 90-min period. Participants' perception of time was manipulated by having them refer to clocks that were either accurate or altered to run fast or slow. Blood glucose levels changed in accordance with how much time they believed had passed instead of how much time had actually passed. These results are an example of the influence psychological processes can directly exert on the body.

Mindfulness as a Protective Factor for the Burden of Caregivers of Amyotrophic Lateral Sclerosis Patients.

OBJECTIVES: Caregivers of people with severe chronic conditions, such as amyotrophic lateral sclerosis (ALS), are at risk of developing depression and anxiety and reduced quality of life. Few studies have explored protective factors in this population and none investigated the role of mindfulness. The study aimed to examine the relationship between mindfulness and health-related outcomes in a population of ALS caregivers. METHODS: We conducted an online survey with ALS caregivers, and again at 4-month follow-up, to assess mindfulness, burden, quality of life, anxiety, and depression. The associations between mindfulness and the other outcomes were evaluated both cross-sectionally and longitudinally. RESULTS: Mindfulness correlated negatively with burden, depression, and anxiety and positively with quality of life, maintaining stability through time. CONCLUSION: Our results showed that mindfulness is positively related to quality of life and negatively related to level of burden. We suggest that this construct can represent a preventative factor toward the negative effects of caregiving.

Mindfulness, physical impairment and psychological well-being in people with amyotrophic lateral sclerosis.

OBJECTIVE: Mindfulness is the process of actively making new distinctions, rather than relying on habitual or automatic categorisations from the past. Mindfulness has been positively associated with physical well-being, better recovery rates from disease or infections, pain reduction and overall quality of life (QOL). Amyotrophic lateral sclerosis (ALS) is a rare, progressive and fatal neurodegenerative disease, clinically characterised by progressively increasing weakness leading to death, usually within five years. There is presently no cure for ALS, and it is considered one of the most genetically and biologically driven illnesses. Thus far, the aims of psychological studies on ALS have focused on understanding patient - and, to a lesser extent, caregiver - QOL and psychological well-being. No previous study has investigated the influence of psychological factors on ALS. METHODS: A sample of 197 subjects with ALS were recruited and assessed online twice, with a duration of four months between the two assessments. Assessments included measurements of trait mindfulness, physical impairment, QOL, anxiety and depression. The influence of mindfulness as predictor of changes in physical impairments was evaluated with a mixed-effects model. RESULTS: Mindfulness positively influenced the change of physical symptoms. Subjects with higher mindfulness experienced a slower progression of the disease after four months. Moreover, mindfulness at first assessment predicted higher QOL and psychological well-being. CONCLUSIONS: The available data indicate that a psychological construct - mindfulness - can attenuate the progress of a disease that is believed to be almost solely biologically driven. The potential implications of these results extend well beyond ALS.