The relationship between attachment representations and minimal intergroup bias in preschool-aged children.

Attachment theory proposes that young children's experiences with their caregivers has a tremendous influence on how children navigate their social relationships. By the end of early childhood, intergroup contexts play an important role in their social life and children build strong ties to their ingroups. Although both domains relate to the same psychological processes-children's affective ties to others-surprisingly very little research has addressed how children's attachment relates to their intergroup attitudes and behavior. In this study, we investigate the link. For that purpose, 5-year-old children (n = 100) first underwent the German Attachment Story Completion Task (GEV-B). Then we allocated children into minimal groups based on T-Shirt color and assessed their intergroup attitudes and intergroup behavior. Results showed that while most children showed a strong and robust ingroup bias in their attitudes and behavior, children with an insecure-ambivalent attachment representation treated in- and outgroup similarly. Overall, this study provides novel perspectives on the relationship between children's attachment representation and their interactions in the social world. RESEARCH HIGHLIGHTS: This study provides novel insights into the relationship between children's attachment security and the development of intergroup bias in a minimal group context Children with secure, insecure-avoidant and disorganized attachment representation showed a strong intergroup bias in explicit attitudes and behavior Children with insecure-ambivalent attachment representation displayed no intergroup bias Insecure-ambivalent attachment representations might be detrimental to the formation of ingroup attachment.

Adaptation to pollination by fungus gnats underlies the evolution of pollination syndrome in the genus Euonymus.

BACKGROUND AND AIMS: Dipteran insects are known pollinators of many angiosperms, but knowledge on how flies affect floral evolution is relatively scarce. Some plants pollinated by fungus gnats share a unique set of floral characters (dark red display, flat shape and short stamens), which differs from any known pollination syndromes. We tested whether this set of floral characters is a pollination syndrome associated with pollination by fungus gnats, using the genus Euonymus as a model. METHODS: The pollinator and floral colour, morphology and scent profile were investigated for ten Euonymus species and Tripterygium regelii as an outgroup. The flower colour was evaluated using bee and fly colour vision models. The evolutionary association between fungus gnat pollination and each plant character was tested using a phylogenetically independent contrast. The ancestral state reconstruction was performed on flower colour, which is associated with fungus gnat pollination, to infer the evolution of pollination in the genus Euonymus. KEY RESULTS: The red-flowered Euonymus species were pollinated predominantly by fungus gnats, whereas the white-flowered species were pollinated by bees, beetles and brachyceran flies. The colour vision analysis suggested that red and white flowers are perceived as different colours by both bees and flies. The floral scents of the fungus gnat-pollinated species were characterized by acetoin, which made up >90 % of the total scent in three species. Phylogenetically independent contrast showed that the evolution of fungus gnat pollination is associated with acquisition of red flowers, short stamens and acetoin emission. CONCLUSIONS: Our results suggest that the observed combination of floral characters is a pollination syndrome associated with the parallel evolution of pollination by fungus gnats. Although the role of the red floral display and acetoin in pollinator attraction remains to be elucidated, our finding underscores the importance of fungus gnats as potential contributors to floral diversification.

The non-apoptotic function of Caspase-8 in negatively regulating the CDK9-mediated Ser2 phosphorylation of RNA polymerase II in cervical cancer.

Cervical cancer is the fourth most frequently diagnosed and fatal gynecological cancer. 15-61% of all cases metastasize and develop chemoresistance, reducing the 5-year survival of cervical cancer patients to as low as 17%. Therefore, unraveling the mechanisms contributing to metastasis is critical in developing better-targeted therapies against it. Here, we have identified a novel mechanism where nuclear Caspase-8 directly interacts with and inhibits the activity of CDK9, thereby modulating RNAPII-mediated global transcription, including those of cell-migration- and cell-invasion-associated genes. Crucially, low Caspase-8 expression in cervical cancer patients leads to poor prognosis, higher CDK9 phosphorylation at Thr186, and increased RNAPII activity in cervical cancer cell lines and patient biopsies. Caspase-8 knock-out cells were also more resistant to the small-molecule CDK9 inhibitor BAY1251152 in both 2D- and 3D-culture conditions. Combining BAY1251152 with Cisplatin synergistically overcame chemoresistance of Caspase-8-deficient cervical cancer cells. Therefore, Caspase-8 expression could be a marker in chemoresistant cervical tumors, suggesting CDK9 inhibitor treatment for their sensitization to Cisplatin-based chemotherapy.

The Effectiveness of A Slow-Paced Diaphragmatic Breathing Exercise in Children's Daily Life: A Micro-Randomized Trial.

OBJECTIVE: Breathing exercises have been proposed as an effective intervention to improve subjective well-being and manage anxiety symptoms. As they are comparatively easy to learn and to implement, breathing exercises may be particularly beneficial for children. Although breathing exercises are ultimately supposed to provide salutary effects in individuals' everyday lives, immediate effects of breathing exercises in naturalistic contexts have received limited empirical attention. The purpose of this study was to examine immediate effects of slow-paced diaphragmatic breathing on negative affect as well as on relaxation in an ecologically valid setting. To that end, we conducted a micro-randomized trial in children's daily life. METHOD: On each of 15 days, children (N = 171, aged 9-13 years, 54% female) were randomized to different conditions: performing a video-guided slow-paced diaphragmatic breathing exercise (experimental condition), watching a different video (active control condition), or a passive control condition. RESULTS: The breathing exercise had no immediate effects on negative affect or relaxation compared to both control conditions. However, in situations when children reported higher levels of worries than usual, relaxation was higher when children performed the breathing exercise compared to the passive control condition. Compared to the active control condition, the breathing exercise did not result in higher levels of relaxation in situations when children worried more than normally. CONCLUSIONS: Findings highlight that context-specific factors can modulate the effectiveness of breathing exercises and should be taken into account to tailor interventions to individuals' needs.

The Critical Intervention Screen: A Novel Tool to Determine the Use of Lights and Sirens during the Transport of Trauma Patients.

Objective: EMS use of lights and sirens has long been employed in EMS systems, despite an increased risk of motor vehicle collisions associated with their use. The specific aims of this study were to assess the current use of lights and sirens during the transport of trauma patients in a busy metropolitan area and to subsequently develop a novel tool, the Critical Intervention Screen, to aid EMS professionals tasked with making transport decisions in the presence of acute injury.Methods: This single-center, retrospective study included all patients transported to an academic Level One trauma center by ground ambulance from the scene of presumed or known injury. A subset of patients was identified as being most likely to benefit from shorter transport times if they received one of the following critical interventions within 20 minutes of emergency department arrival: intubation, thoracotomy, chest tube, blood products, central line, arterial line, REBOA, disposition to an operating room, or death. Stepwise logistic regression was employed for the development of the Critical Intervention Screen, with a subset of data retained for internal validation.Results: 1296 patients were available for analysis. Overall, 217 patients (16.7%) received a critical intervention, and 112 patients (8.6%) of those patients received a critical intervention within 20 minutes of emergency department arrival. At baseline, EMS use of lights and sirens was 91.1% sensitive and 80.3% specific for receiving a critical intervention. Stepwise logistic regression demonstrated that the need for assisted ventilation, GCS Motor < 6, and penetrating trauma to the trunk were the most predictive prehospital data for receiving at least one critical intervention. The Critical Intervention Screen, defined as having at least one of these risk factors in the prehospital setting, modestly increased sensitivity and specificity (96.4% and 87.9%, respectively) predicting the need for a critical intervention.Conclusion: These findings indicate that EMS are able to correctly identify high-acuity trauma patients, but at times employ L&S during the transport of patients with a low likelihood of receiving a time-sensitive intervention upon emergency department arrival. Therefore, the Critical Intervention Screen has the potential to reduce the use of lights and sirens and improve EMS safety.

Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours.

A Little Autonomy Support Goes a Long Way: Daily Autonomy-Supportive Parenting, Child Well-Being, Parental Need Fulfillment, and Change in Child, Family, and Parent Adjustment Across the Adaptation to the COVID-19 Pandemic.

This study examined the effects of daily parental autonomy support on changes in child behavior, family environment, and parental well-being across 3 weeks during the COVID-19 pandemic in Germany. Day-to-day associations among autonomy-supportive parenting, parental need fulfillment, and child well-being were also assessed. Parents (longitudinal N = 469; Mage  = 42.93, SDage  = 6.40) of school children (6-19 years) reported on adjustment measures at two measurement occasions and completed up to 21 daily online questionnaires in the weeks between these assessments. Results from dynamic structural equation models suggested reciprocal positive relations among autonomy-supportive parenting and parental need fulfillment. Daily parental autonomy support, parental need fulfillment, and child well-being partially predicted change in adjustment measures highlighting the central role of daily parenting for children's adjustment during the pandemic.

Change in mental health symptoms during the COVID-19 pandemic: The role of appraisals and daily life experiences.

OBJECTIVE: When confronted with major threats, people often experience decline in well-being. The central purpose of this study was to identify mechanisms underlying change of well-being in times of threat, using the example of the COVID-19 pandemic, with a focus on appraisals of the pandemic and affective states, stress, as well as mindfulness in daily life. METHOD: We conducted a study across 3.5 weeks, including pretest, posttest, and a diary phase in-between. We worked with a sample of 460 adults, pre- and post-test information, as well as 7,189 observations from the diary phase. RESULTS: Results showed that deterioration in mental health symptoms across the duration of the study was associated with (a) change towards less fortunate appraisals of the pandemic and (b), more negative affect and less mindfulness in daily life. Furthermore, appraisals of the pandemic at pretest predicted experiences in daily life, with more negative appraisals of the pandemic predicting more negative affect and stressor occurrence as well as less mindfulness. CONCLUSIONS: These findings speak to the dynamic nature of well-being and appraisals in times of threat, and highlight the role of experiences in daily life in changes in well-being.

Boosting the apoptotic response of high-grade serous ovarian cancers with CCNE1 amplification to paclitaxel in vitro by targeting APC/C and the pro-survival protein MCL-1.

Ovarian cancer exhibits the highest mortality rate among gynecological malignancies. Antimitotic agents, such as paclitaxel, are frontline drugs for the treatment of ovarian cancer. They inhibit microtubule dynamics and their efficiency relies on a prolonged mitotic arrest and the strong activation of the spindle assembly checkpoint (SAC). Although ovarian cancers respond well to paclitaxel, the clinical efficacy is limited due to an early onset of drug resistance, which may rely on a compromised mitosis exit associated with weakend intrinsic apoptosis. Accordingly, we aimed at overcoming SAC silencing that occurs rapidly during paclitaxel-induced mitotic arrest. To do this, we used a specific anaphase-promoting complex/cyclosome (APC/C) inhibitor to prevent a premature mitotic exit upon paclitaxel treatment. Furthermore, we investigated the role of the antiapoptotic BCL-2 family member MCL-1 in determining the fate of ovarian cancer cells lines with CCNE1 amplification that are challenged with clinically relevant dose of paclitaxel. Using time-laps microscopy, we demonstrated that APC/C and MCL-1 inhibition under paclitaxel prevents mitotic slippage in ovarian cancer cell lines and restores death in mitosis. Consistent with this, the combinatorial treatment reduced the survival of ovarian cancer cells in 2D and 3D cell models. Since a therapeutic ceiling has been reached with taxanes, it is of utmost importance to develop alternative strategies to improve the patient's survival. Thus, our study provides not only elements to understand the causes of taxane resistance in CCNE1-amplified ovarian cancers but also suggests a new combinatorial strategy that may improve paclitaxel-based efficacy in this highly lethal gynecological disease.

Taxonomic similarity does not predict necessary sample size for ex situ conservation: a comparison among five genera.

Effectively conserving biodiversity with limited resources requires scientifically informed and efficient strategies. Guidance is particularly needed on how many living plants are necessary to conserve a threshold level of genetic diversity in ex situ collections. We investigated this question for 11 taxa across five genera. In this first study analysing and optimizing ex situ genetic diversity across multiple genera, we found that the percentage of extant genetic diversity currently conserved varies among taxa from 40% to 95%. Most taxa are well below genetic conservation targets. Resampling datasets showed that ideal collection sizes vary widely even within a genus: one taxon typically required at least 50% more individuals than another (though Quercus was an exception). Still, across taxa, the minimum collection size to achieve genetic conservation goals is within one order of magnitude. Current collections are also suboptimal: they could remain the same size yet capture twice the genetic diversity with an improved sampling design. We term this deficiency the 'genetic conservation gap'. Lastly, we show that minimum collection sizes are influenced by collection priorities regarding the genetic diversity target. In summary, current collections are insufficient (not reaching targets) and suboptimal (not efficiently designed), and we show how improvements can be made.

The right trait in the right place at the right time: Matching traits to environment improves restoration outcomes.

The challenges of restoration in dryland ecosystems are growing due to a rise in anthropogenic disturbance and increasing aridity. Plant functional traits are often used to predict plant performance and can offer a window into potential outcomes of restoration efforts across environmental gradients. We analyzed a database including 15 yr of seeding outcomes across 150 sites on the Colorado Plateau, a cold desert ecoregion in the western United States, and analyzed the independent and interactive effects of functional traits (seed mass, height, and specific leaf area) and local biologically relevant climate variables on seeding success. We predicted that the best models would include an interaction between plant traits and climate, indicating a need to match the right trait value to the right climate conditions to maximize seeding success. Indeed, we found that both plant height and seed size significantly interacted with temperature seasonality, with larger seeds and taller plants performing better in more seasonal environments. We also determined that these trait-environment patterns are not influenced by whether a species is native or nonnative. Our results inform the selection of seed mixes for restoring areas with specific climatic conditions, while also demonstrating the strong influence of temperature seasonality on seeding success in the Colorado Plateau region.

Applying the zoo model to conservation of threatened exceptional plant species.

Maintaining a living plant collection is the most common method of ex situ conservation for plant species that cannot be seed banked (i.e., exceptional species). Viability of living collections, and their value for future conservation efforts, can be limited without coordinated efforts to track and manage individuals across institutions. Using a pedigree-focused approach, the zoological community has established an inter-institutional infrastructure to support long-term viability of captive animal populations. We assessed the ability of this coordinated metacollection infrastructure to support the conservation of 4 plant species curated in living collections at multiple botanic gardens around the world. Limitations in current practices include the inability to compile, share, and analyze plant collections data at the individual level, as well as difficulty in tracking original provenance of ex situ material. The coordinated metacollection framework used by zoos can be adopted by the botanical community to improve conservation outcomes by minimizing the loss of genetic diversity in collections. We suggest actions to improve ex situ conservation of exceptional plant species, including developing a central database to aggregate data and track unique individuals of priority threatened species among institutions and adapting a pedigree-based population management tool that incorporates life-history aspects unique to plants. If approached collaboratively across regional, national, and global scales, these actions could transform ex situ conservation of threatened plant species.

Aplicación del Modelo Zoológico a la Conservación de Especies Excepcionales de Plantas Amenazadas Resumen El mantenimiento de una colección de plantas vivas es el método más común para de conservación ex situ para especies de plantas que no pueden almacenarse en bancos de semillas (i. e., especies excepcionales). La viabilidad de las colecciones vivientes, junto con el valor que representan para los futuros esfuerzo de conservación, puede estar limitada si no existen esfuerzos coordinados para rastrear y manejar a los individuos entre las instituciones. Mediante una estrategia enfocada en el linaje, la comunidad de zoológicos ha establecido una infraestructura interinstitucional que respalda la viabilidad a largo plazo de las poblaciones de animales en cautiverio. Evaluamos la habilidad de esta infraestructura coordinada de metacolecciones para apoyar en la conservación de cuatro especies de plantas curadas en colecciones vivientes en varios jardines botánicos de todo el mundo. Las limitaciones de las prácticas contemporáneas incluyen la incapacidad de recopilar, compartir y analizar los datos de las colecciones de plantas a nivel individual, así como la dificultad de rastrear la procedencia original del material ex situ. El marco de trabajo de metacolecciones coordinadas que utilizan los zoológicos puede ser adoptado por la comunidad botánica para mejorar los resultados de conservación al minimizar la pérdida de la diversidad genética que ocurre en las colecciones. Sugerimos acciones que aumenten la conservación ex situ de las especies excepcionales de plantas. Estas acciones incluyen el desarrollo de una base de datos central para acumular datos y rastrear entre las instituciones a los individuos únicos de las especies amenazadas prioritarias y la adaptación de una herramienta de manejo poblacional basada en el linaje que incorpore los aspectos únicos de la historia de vida de las plantas. Si estas acciones se plantean colaborativamente a escala regional, nacional y global, podrían transformar la conservación ex situ de las especies amenazadas de plantas.

Ocular Neuromyotonia: Clinical Features, Diagnosis, and Outcomes.

PURPOSE: The purpose of this study was to describe the clinical features, management, outcomes, and diagnostic pitfalls in a large series of patients with ocular neuromyotonia. DESIGN: Retrospective cohort. METHODS: Patients diagnosed with ocular neuromyotonia from January 1, 2004, through January 1, 2023, seen at one of the 3 Mayo Clinic sites in Rochester, MN, Scottsdale, AZ, and Jacksonville, FL, comprised the study population. We ascertained patients with ocular neuromyotonia through a search using the medical records database. Only patients with an observed episode of ocular neuromyotonia were included and the medical records were reviewed. The main outcome measures were clinical features and outcomes of patients with ocular neuromyotonia. RESULTS: Forty-two patients who were diagnosed with ocular neuromyotonia were included. The median age was 58 years (range, 16-80 years). A history of cranial radiation therapy was present in 39 patients (93%). The sixth cranial nerve was involved in 31 patients (74%). Bilateral disease was found in 2 patients (5%). The median time from onset of diplopia to diagnosis was 8 months (range, 1 month-25 years), with a high rate of initial misdiagnosis in 52%. Twenty of 42 patients (48%) were treated with oral medication, of whom 95% had significant improvement or resolution of symptoms. CONCLUSION: Prior cranial irradiation is the most common cause for ocular neuromyotonia, affecting the sixth cranial nerve most often. Although delayed and initial misdiagnosis is common, most patients show improved symptoms on medical treatment.

Characteristics of childhood intermittent exotropia with and without DVD.

Purpose: Although dissociated vertical deviation (DVD) is reported to occur rarely in children with intermittent exotropia (IXT), little is known regarding the clinical features of these children. The purpose of this study was to compare the demographic and clinical characteristics of children with intermittent exotropia and DVD to those without DVD. Methods: The medical records of all children diagnosed with intermittent exotropia at our institution from 1 January 2002, through 31 December 2018, who had 2 or more exams with 3 or more assessments of control, were retrospectively reviewed. Exotropic children with DVD were compared to those without DVD. Results: During the 17-year study period, 115 children met the inclusion criteria, of which 25 (21.7%) had DVD. Compared to the 90 exotropic children without DVD, children with IXT and DVD were more likely to have a motility disorder (p = .021), a worse mean distance control score (2.8 vs 2.4; p = .09), a larger mean angle of deviation (27.8 prism diopters [PD] vs 25.1 PD; p = .04), and a lower median stereopsis (200 secs vs 100 secs; p = .08). The children with DVD were more likely to have undergone surgery (p = .17) although there was no difference in the mean age at initial surgery between the two groups. Conclusions: The presence of dissociated vertical deviation in children with intermittent exotropia is associated with more motility disorders and worse binocular function compared to those without DVD. These children will likely require closer observation and earlier intervention.

Species-specific effects of production practices on genetic diversity in plant reintroduction programs.

Plant production practices can influence the genetic diversity of cultivated plant materials and, ultimately, their potential to adapt to a reintroduction site. A common step in the plant production process is the application of seed pretreatment to alleviate physiological seed dormancy and successfully germinate seeds. In production settings, the seeds that germinate more rapidly may be favored in order to fill plant quotas. In this study, we investigated how the application of cold-moist stratification treatments with different durations can lead to differences in the genetic diversity of the propagated plant materials. Specifically, we exposed seeds of three Viola species to two different cold stratification durations, and then we analyzed the genetic diversity of the resulting subpopulations through double-digestion restriction site-associated sequencing (ddRADseq). Our results show that, in two out of three species, utilizing a short stratification period will decrease the genetic diversity of neutral and expressed loci, likely due to the imposition of a genetic bottleneck and artificial selection. We conclude that, in some species, the use of minimal stratification practices in production may jeopardize the adaptive potential and long-term persistence of reintroduced populations and suggest that practitioners carefully consider the evolutionary implications of their production protocols. We highlight the need to consider the germination ecology of target species when selecting the length of dormancy-breaking pretreatments.

Synergistic Sensitization of High-Grade Serous Ovarian Cancer Cells Lacking Caspase-8 Expression to Chemotherapeutics Using Combinations of Small-Molecule BRD4 and CDK9 Inhibitors.

Ovarian cancer is one of the most lethal gynecological cancers worldwide, with approximately 70% of cases diagnosed in advanced stages. This late diagnosis results from the absence of early warning symptoms and is associated with an unfavorable prognosis. A standard treatment entails a combination of primary chemotherapy with platinum and taxane agents. Tumor recurrence following first-line chemotherapy with Carboplatin and Paclitaxel is detected in 80% of advanced ovarian cancer patients, with disease relapse occurring within 2 years of initial treatment. Platinum-resistant ovarian cancer is one of the biggest challenges in treating patients. Second-line treatments involve PARP or VEGF inhibitors. Identifying novel biomarkers and resistance mechanisms is critical to overcoming resistance, developing newer treatment strategies, and improving patient survival. In this study, we have determined that low Caspase-8 expression in ovarian cancer patients leads to poor prognosis. High-Grade Serous Ovarian Cancer (HGSOC) cells lacking Caspase-8 expression showed an altered composition of the RNA Polymerase II-containing transcriptional elongation complex leading to increased transcriptional activity. Caspase-8 knockout cells display increased BRD4 expression and CDK9 activity and reduced sensitivities to Carboplatin and Paclitaxel. Based on our work, we are proposing three potential therapeutic approaches to treat advanced ovarian cancer patients who exhibit low Caspase-8 expression and resistance to Carboplatin and/or Paclitaxel-combinations of (1) Carboplatin with small-molecule BRD4 inhibitors; (2) Paclitaxel with small-molecule BRD4 inhibitors, and (3) small-molecule BRD4 and CDK9 inhibitors. In addition, we are also proposing two predictive markers of chemoresistance-BRD4 and pCDK9.

Polo-box domain inhibitor poloxin activates the spindle assembly checkpoint and inhibits tumor growth in vivo.

Polo-like kinase 1 (Plk1) is widely established as one of the most promising targets in oncology. Although the protein kinase domain of Plk1 is highly conserved, the polo-box domain (PBD) of Plk1 provides a much more compelling site to specifically inhibit the localization and target binding of Plk1. We recently identified, via fluorescence polarization assay, the natural product derivative, Poloxin, as the first small-molecule inhibitor specifically targeting the function of the Plk1 PBD. In this study, we characterized its mitotic phenotype and its function in vitro and in vivo. Poloxin induces centrosome fragmentation and abnormal spindle and chromosome misalignment, which activate the spindle assembly checkpoint and prolong mitosis. Notably, centrosomal fragmentation induced by Poloxin is partially attributable to dysfunctional Kizuna, a key substrate of Plk1 at centrosomes. Moreover, Poloxin strongly inhibits proliferation of a panel of cancer cells by inducing mitotic arrest, followed by a surge of apoptosis. More important, we report, for the first time to our knowledge, that the PBD inhibitor, Poloxin, significantly suppresses tumor growth of cancer cell lines in xenograft mouse models by lowering the proliferation rate and triggering apoptosis in treated tumor tissues. The data highlight that targeting the PBD by Poloxin is a powerful approach for selectively inhibiting Plk1 function in vitro and in vivo.

Assessing domain-general need fulfillment in children and adults: Introducing the General Need Satisfaction and Frustration scale.

Fulfillment of basic psychological needs has been postulated to be essential for mental health across the human life span. So far, validated domain-general instruments using the same items to assess these constructs in different age groups are lacking. To close this gap, we introduce the General Need Satisfaction and Frustration scale, a multidimensional instrument to capture fulfillment of the basic psychological needs for autonomy, competence, and relatedness in children and adults. The factor structure and correlates of this new instrument are examined in two cross-sectional studies with children (N = 185, age range = 7-14) and adults (N = 380, age range = 18-77), and one ambulatory assessment study with children (N = 84, age range = 8-10). Confirmatory factor analyses suggest adequate fit of the postulated six-dimensional measurement model (three needs, each split into satisfaction and frustration). Need satisfaction was linked to higher well-being, and need frustration was linked to higher ill-being in both children and adults. Findings suggest that the instrument introduced in this work is suitable to capture between-person differences as well as day-to-day fluctuations in the fulfillment of the basic needs for autonomy, competence, and relatedness in children and adults. The measurement instrument therefore is a useful tool to capture core ingredients for mental health in samples across a broad range of the human life span. (PsycInfo Database Record (c) 2022 APA, all rights reserved).