Does Prospective Mental Imagery Predict Symptoms of Negative Affect and Anhedonia in Young People?

Adolescent depression is associated with unhelpful emotional mental imagery. Here, we investigated whether vividness of negative and positive prospective mental imagery predict negative affect and anhedonia in adolescents. 111 people from Israel completed measures of prospective mental imagery, negative affect, and anhedonia at two time-points approximately three months apart. Using three cross-lagged panel models, we showed once 'concurrent' (across-variable, within-time) and 'stability' paths (across-time, within-variable) were estimated, there were no significant cross-lag paths between: i) T1 prospective negative mental imagery and T8 negative affect (i.e. increased vividness of negative future imagery at Time 1 did not predict increased negative affect at Time 8); ii) T1 prospective positive mental imagery and T8 negative affect (i.e. reduced vividness of positive future imagery at Time 1 did not predict increased negative affect at Time 8); and iii) T1 prospective positive mental imagery and T8 anhedonia (i.e. reduced vividness of positive future imagery at Time 1 did not predict increased anhedonia at Time 8). Given high levels of attrition, future research should aim to explore these associations in a larger, more diverse population, as such data could inform on whether modifying earlier prospective mental imagery may influence later time/context-specific effects of prospective mental imagery on negative affect and anhedonia.

Structural rearrangements in the nucleus localize latent HIV proviruses to a perinucleolar compartment supportive of reactivation.

Using an immunofluorescence assay based on CRISPR-dCas9-gRNA complexes that selectively bind to the HIV LTR (HIV Cas-FISH), we traced changes in HIV DNA localization in primary effector T cells from early infection until the cells become quiescent as they transition to memory cells. Unintegrated HIV DNA colocalized with CPSF6 and HIV capsid (CA, p24) was found in the cytoplasm and nuclear periphery at days 1 and 3 post infection. From days 3 to 7, most HIV DNA was distributed primarily in the nuclear intermediate euchromatic compartment and was transcribed. By day 21, the cells had entered quiescence, and HIV DNA accumulated in the perinucleolar compartment (PNC). The localization of proviruses to the PNC was blocked by integrase inhibitor Raltegravir, suggesting it was due to chromosomal rearrangements. During the reactivation of latently infected cells through the T cell receptor (TCR), nascent viral mRNA transcripts associated with HIV DNA in the PNC were detected. The viral trans-activator Tat and its regulatory partners, P-TEFb and 7SK snRNA, assembled in large interchromatin granule clusters near the provirus within 2 h of TCR activation. As T cell activation progressed, the HIV DNA shifted away from the PNC. HIV DNA in latently infected memory T cells from patients also accumulated in the PNC and showed identical patterns of nuclear rearrangements after cellular reactivation. Thus, in contrast to transformed cells where proviruses are found primarily at the nuclear periphery, in primary memory T cells, the nuclear architecture undergoes rearrangements that shape the transcriptional silencing and reactivation of proviral HIV.

Identifying characteristics of adolescents with persistent loneliness during COVID-19: A multi-country eight-wave longitudinal study.

Background: Elevated loneliness experiences characterise young people. While loneliness at this developmental juncture may emerge from age-typical upheaval in social relationships, there is little data on the extent to which young people experience high and persistent levels of loneliness, and importantly, who is most vulnerable to these experiences. Using the widespread social restrictions associated with the COVID-19 pandemic, which precipitated loneliness in many, we aimed to examine adolescents' loneliness profiles across time and the demographic predictors (age, sex, and country) of more severe trajectories. Methods: Participants aged 12-18 years, recruited into a multi-wave study (N = 1039) across three sites (UK, Israel, and India) completed a 3-item loneliness measure fortnightly across 8 timepoints during the pandemic. Results: Latent class growth analysis suggested 5 distinct trajectories: (1) low stable (33%), (2) low increasing (19%), (3) moderate decreasing (17%), (4) moderate stable (23%), and (5) high increasing (8%). Females and older adolescents were more likely to experience persistently high loneliness. Conclusions: These findings indicate a need for interventions to reduce loneliness in adolescents as we emerge from the pandemic, particularly for those groups identified as being at highest risk.

Emotional dampening in hypertension: Impaired recognition of implicit emotional content in auditory and cross-modal stimuli.

Research shows a reduced responsivity to implicit as well as explicit facial emotion recognition (emotional dampening) in prehypertensives and hypertensives. This study explored auditory and audiovisual emotion recognition in prehypertensives and hypertensives. Participants (N = 175) who were normotensives, prehypertensives, and hypertensives (n = 57, 58, and 60, respectively) completed an auditory implicit task (matching auditory target with auditory distractors) and two cross-modal implicit tasks (matching visual target with auditory distractors, and vice-versa), and an auditory explicit task (labelling emotions in audio-clips). Findings showed an aberrant speed-accuracy trade-off, where prehypertensives focused more on accuracy at the cost of speed while hypertensives showed the opposite. Discriminant function analysis revealed that blood pressure (BP)-associated emotional dampening is a highly specific but moderately sensitive correlate of hypertension. Our study highlights that prehypertensives and hypertensives demonstrate emotional dampening in implicit (but not explicit) auditory emotion recognition and a greater deficit for auditory than visual recognition of implicit emotions. Findings show emotional dampening as an observable correlate of elevated BP and hypertension.

Attenuated maladaptive emotion processing as a potential mediator of the relationship between dispositional mindfulness and mental health.

The emotion processing and regulation mechanisms by which dispositional (personality trait) mindfulness exerts its positive effects on mental health remain unclear. Here, we tested, using structural equation modeling, whether the relationship between higher dispositional mindfulness and better mental health is mediated by reduced maladaptive processing of emotional information (e.g., expressive suppression, impoverished emotional experiences, unprocessed emotions, avoidance, externalizing strategies) and associated lower negative affect, enhanced adaptive processing of emotional information (e.g., cognitive reappraisal) and associated higher positive affect, or a combination of these two emotion processing styles. Dispositional mindfulness, mental health, diverse emotional constructs with adaptive and maladaptive dimensions (including range and differentiation of emotional experiences, use of specific emotion regulation strategies, emotion processing deficits, negative affect repair strategies, negative mood regulation expectancies), and positive and negative affect were assessed using self-report measures in a non-clinical sample of 256 adults. The relationship between higher dispositional mindfulness and better mental health was found to be best explained by reduced maladaptive emotion processing styles and associated lower negative affect, rather than by enhanced adaptive emotion processing and higher positive affect. Further research should investigate whether the same mechanisms explain psychological benefits of cultivated mindfulness in people with low dispositional mindfulness and/or with mental health disorders following mindfulness skills training.

Self-Reported Worries in Young People During the COVID-19 Pandemic.

Purpose: COVID-19 pandemic has had long-standing consequences for all aspects of life. Although young people appear less susceptible to severe forms of physical illness due to the coronavirus, they have not escaped unscathed from its' psychological impacts. The present study measured the content of worries in young people residing in the UK during the pandemic and how it varied with sociodemographic factors. Methods: Between May and December 2020, UK-residing participants aged 12-25 years completed an online survey that presented participants with free-text fields to describe their top three worries over the last two weeks, in addition to demographic and other information. Cross-sectional data from 2560 participants (Males = 767; Female = 1793) was analyzed. Results: Irrespective of sociodemographic, a majority of the participants reported worries related to academics, followed by social relationships, own physical health, social and work routines, and physical health of others. Significantly more females reported concerns about academics, finances, physical health, social and work routines, social relationships, mental health and emotions, and physical health of others. Expectedly, more older (18-25 years) than younger (12-17 years) participants reported concerns about career-prospects and finances, while more younger than older ones were worried about academics (98.41% vs. 80.90%). With respect to financial worries, a higher percentage of BAME (Black, Asian and Minority Ethnic) communities in the UK reported such worries. Ethnicity significantly predicted more worries about social relationships among White than BAME participants. Significant differences also existed across different SES groups regarding endorsement of a particular category of worry. Conclusion: These findings highlight the need for tailored interventions depending on the major concerns for young people of different ages, sexes, ethnicities, and SES. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-023-10396-3.

Is Future Mental Imagery Associated with Reduced Impact of the COVID-19 Pandemic on Negative Affect and Anhedonic Symptoms in Young People?

Background: Difficulties with prospective mental images are associated with adolescent depression. Current treatments mainly focus on verbal techniques to reduce negative affect (e.g. low mood) rather than enhancing positive affect, despite anhedonia being present in adolescents. We investigated the concurrent relationships between the vividness of negative and positive prospective mental imagery and negative affect and positive affect; and examined whether negative and positive prospective mental imagery moderated the impact of recent stress (COVID-19-linked stress) on negative and positive affect. Methods: 2602 young people (12-25 years) completed the Prospective Imagery Task and self-reported on symptoms of negative affect, anhedonia and COVID-19 linked stress. Results: Elevated vividness of negative future mental imagery and reduced vividness of positive future mental imagery were associated with increased negative affect, whereas only reduced vividness of positive future imagery was associated with increased symptoms of anhedonia. Elevated vividness of negative future images amplified the association between COVID-19 linked stress and negative affect, while elevated vividness of positive future images attenuated the association between COVID-19 linked stress and anhedonia. Conclusions: Future mental imagery may be differentially associated with negative and positive affect, but this needs to be replicated in clinical populations to support novel adolescent psychological treatments. Supplementary Information: The online version contains supplementary material available at 10.1007/s10608-023-10352-1.

Behavioural approach-avoidance tendencies among individuals with elevated blood pressure.

Emotional dampening (blunted responses to affective stimuli or experiences) has been reported in individuals with clinical and subclinical levels of elevated blood pressure (BP). Our aim in the present study was to explore how the basic motivational systems of approach and avoidance to positively- and negatively-valenced stimuli are affected in elevated BP. High BP (n = 27) and Low BP (n = 29) participants completed an approach-avoidance task. In this task, participants pulled the joystick towards them when viewing a happy face (approach) and pushing it away when viewing an angry face (avoid) in the congruent condition, and reversed these action-to-emotion pairings in the incongruent condition. A mixed-design ANOVA revealed a significant main effect of condition, such that overall participants were faster across trials in the congruent than trials of the incongruent condition. There was also an emotion x BP interaction. Among the Low BP group, there were no RT differences to happy and angry expressions (across congruent and incongruent conditions) but those with High BP were quicker to respond to actions paired with angry than happy facial expressions (across conditions). Findings suggest that valence-specific motivational reactions are not dampened with an increase in BP, and are rather sensitized for the negative emotion of anger. Supplementary information: The online version contains supplementary material available at 10.1007/s12144-023-04337-2.

A Reliable Primary Cell Model for HIV Latency: The QUECEL (Quiescent Effector Cell Latency) Method.

One of the main methods to generate the HIV reservoir is during the transition of infected activated effector CD4 T cells to a memory phenotype. The QUECEL (Quiescent Effector Cell Latency) protocol mimics this process efficiently and allows for production of large numbers of latently infected CD4+ T cells. After polarization and expansion, CD4+ T cells are infected with a single round reporter virus which expressed GFP/CD8a. The infected cells are purified and coerced into quiescence using a defined cocktail of cytokines including TGF-ß, IL-10, and IL-8, producing a homogeneous population of latently infected cells. Since homogeneous populations of latently infected cells can be recovered, the QUECEL model has an excellent signal-to-noise ratio, and has been extremely consistent and reproducible in numerous experiments performed during the last 5 years. The ease, efficiency, and accurate mimicking of physiological conditions make the QUECEL model a robust and reproducible tool to study the molecular mechanisms underlying HIV latency.

A network analysis of adolescent mental well-being during the coronavirus pandemic: Evidence for cross-cultural differences in central features.

The COVID-19 pandemic continues to pose unprecedented threat globally. Adolescents and youth may be especially susceptible to the long-term impact of these stressors, thus intervening early is an important priority. However, it is also crucial to understand how young people maintain psychological well-being in the face of adversity, particularly given that many nations are experiencing further waves of the pandemic. The understanding of such resilient outcomes could inform the development of programs to encourage positive mental health.We explored adolescents' resilience to the COVID-19 pandemic stress by examining core aspects of well-being across countries using network analysis. Using the short Warwick-Edinburgh Mental Wellbeing Scale, cross-sectional data was collected online from adolescents from India (N = 310; Males = 159, Females = 151, aged 12-18 years), Israel (N = 306; Males = 154, Females = 152, aged 12-18 years) and the United Kingdom (UK; N = 1666; Males = 598, Females = 1068, aged 12-25 years). Two highly similar network clusters were identified for UK and Israel, with three clusters emerging for India. UK and Israeli networks centred on "dealing with problems well" while the Indian network centred on "feeling useful". As central items highlight aspects of well-being that influence or are influenced by other aspects, these findings may inform interventions to safeguard adolescent mental health during future phases of the pandemic.

Inhibition of the H3K27 demethylase UTX enhances the epigenetic silencing of HIV proviruses and induces HIV-1 DNA hypermethylation but fails to permanently block HIV reactivation.

One strategy for a functional cure of HIV-1 is "block and lock", which seeks to permanently suppress the rebound of quiescent HIV-1 by epigenetic silencing. For the bivalent promoter in the HIV LTR, both histone 3 lysine 27 tri-methylation (H3K27me3) and DNA methylation are associated with viral suppression, while H3K4 tri-methylation (H3K4me3) is correlated with viral expression. However, H3K27me3 is readily reversed upon activation of T-cells through the T-cell receptor. In an attempt to suppress latent HIV-1 in a stable fashion, we knocked down the expression or inhibited the activity of UTX/KDM6A, the major H3K27 demethylase, and investigated its impact on latent HIV-1 reactivation in T cells. Inhibition of UTX dramatically enhanced H3K27me3 levels at the HIV LTR and was associated with increased DNA methylation. In latently infected cells from patients, GSK-J4, which is a potent dual inhibitor of the H3K27me3/me2-demethylases JMJD3/KDM6B and UTX/KDM6A, effectively suppressed the reactivation of latent HIV-1 and also induced DNA methylation at specific sites in the 5'LTR of latent HIV-1 by the enhanced recruitment of DNMT3A to HIV-1. Nonetheless, suppression of HIV-1 through epigenetic silencing required the continued treatment with GSK-J4 and was rapidly reversed after removal of the drug. DNA methylation was also rapidly lost after removal of drug, suggesting active and rapid DNA-demethylation of the HIV LTR. Thus, induction of epigenetic silencing by histone and DNA methylation appears to be insufficient to permanently silence HIV-1 proviral transcription.

Biogenesis of P-TEFb in CD4+ T cells to reverse HIV latency is mediated by protein kinase C (PKC)-independent signaling pathways.

The switch between HIV latency and productive transcription is regulated by an auto-feedback mechanism initiated by the viral trans-activator Tat, which functions to recruit the host transcription elongation factor P-TEFb to proviral HIV. A heterodimeric complex of CDK9 and one of three cyclin T subunits, P-TEFb is expressed at vanishingly low levels in resting memory CD4+ T cells and cellular mechanisms controlling its availability are central to regulation of the emergence of HIV from latency. Using a well-characterized primary T-cell model of HIV latency alongside healthy donor memory CD4+ T cells, we characterized specific T-cell receptor (TCR) signaling pathways that regulate the generation of transcriptionally active P-TEFb, defined as the coordinate expression of cyclin T1 and phospho-Ser175 CDK9. Protein kinase C (PKC) agonists, such as ingenol and prostratin, stimulated active P-TEFb expression and reactivated latent HIV with minimal cytotoxicity, even in the absence of intracellular calcium mobilization with an ionophore. Unexpectedly, inhibition-based experiments demonstrated that PKC agonists and TCR-mobilized diacylglycerol signal through MAP kinases ERK1/2 rather than through PKC to effect the reactivation of both P-TEFb and latent HIV. Single-cell and bulk RNA-seq analyses revealed that of the four known isoforms of the Ras guanine nucleotide exchange factor RasGRP, RasGRP1 is by far the predominantly expressed diacylglycerol-dependent isoform in CD4+ T cells. RasGRP1 should therefore mediate the activation of ERK1/2 via Ras-Raf signaling upon TCR co-stimulation or PKC agonist challenge. Combined inhibition of the PI3K-mTORC2-AKT-mTORC1 pathway and the ERK1/2 activator MEK prior to TCR co-stimulation abrogated active P-TEFb expression and substantially suppressed latent HIV reactivation. Therefore, contrary to prevailing models, the coordinate reactivation of P-TEFb and latent HIV in primary T cells following either TCR co-stimulation or PKC agonist challenge is independent of PKC but rather involves two complementary signaling arms of the TCR cascade, namely, RasGRP1-Ras-Raf-MEK-ERK1/2 and PI3K-mTORC2-AKT-mTORC1.

The Effect of COVID-19 and Related Lockdown Phases on Young Peoples' Worries and Emotions: Novel Data From India.

The COVID-19 pandemic has posed unprecedented stress to young people. Despite recent speculative suggestions of poorer mental health in young people in India since the start of the pandemic, there have been no systematic efforts to measure these. Here we report on the content of worries of Indian adolescents and identify groups of young people who may be particularly vulnerable to negative emotions along with reporting on the impact of coronavirus on their lives. Three-hundred-and-ten young people from North India (51% male, 12-18 years) reported on their personal experiences of being infected by the coronavirus, the impact of the pandemic and its' restrictions across life domains, their top worries, social restrictions, and levels of negative affect and anhedonia. Findings showed that most participants had no personal experience (97.41%) or knew anyone (82.58%) with COVID-19, yet endorsed moderate-to-severe impact of COVID-19 on their academics, social life, and work. These impacts in turn associated with negative affect. Participants' top worries focused on academic attainments, social and recreational activities, and physical health. More females than males worried about academic attainment and physical health while more males worried about social and recreational activities. Thus, Indian adolescents report significant impact of the pandemic on various aspects of their life and are particularly worried about academic attainments, social and recreational activities and physical health. These findings call for a need to ensure provisions and access to digital education and medical care.

Design, synthesis and cytotoxic evaluation of truncated 3'-deoxy- 3', 3' difluororibofuranosyl pyrimidine nucleosides.

Truncated 3'-deoxy- 3', 3' difluororibofuranosyl pyrimidine nucleoside derivatives were synthesized from d-ribose via ß-apioribo pyrimidine nucleoside intermediates 11a-c. The synthetic approach signifies that truncation at C3' position of apioribose ring of 13a-c by oxidative cleavage of diols with Pb(OAc)4 and followed by fluorination with DAST as key steps. Cytotoxic evaluation of synthesized truncated nucleoside derivatives 16a-c and 19a-c were tested against MCF7 and MDA-MB-231 breast cancer cell lines. However, only 19a was shown minimal growth suppression activity on MDA-MB-231 cancer cell lines.

Reduced emotional responsiveness in individuals with marginal elevation in blood pressure within the normal range: Evidence from altered affect-modulated startle response.

Reduced responsiveness to emotional stimuli ('emotional dampening') has been observed in normotensives with elevated blood pressure (BP) and hypertensives but it is not known whether this is due to aberrant responding to emotional information at the involuntary level and whether it is also associated with minimal elevations in BP in the normal range. In this study, we examined emotional dampening using the affect-modulated startle paradigm given its proven sensitivity to motivational states of approach and withdrawal, typically independent of conscious intentional control. Acoustically elicited startle eye-blink modulation was measured using electromyography of the orbicularis oculi muscle beneath the left eye in 59 healthy individuals while they viewed pleasant, unpleasant and neutral standardized pictures. The expected startle attenuation to pleasant pictures, and startle potentiation to unpleasant pictures, relative to neutral pictures, was found in people in the comparison (N = 29) but not elevated BP (N = 30) group. This finding was further supported by significant moderating effect (assessed using ANCOVA and sub-sample analysis) of BP on valence-startle amplitude relationship. The comparison BP group also showed slower latencies to response onset for pleasant stimuli compared to neutral and unpleasant, with no effect of valence in the elevated BP group. However, BP did not moderate the valence-onset latency relationship. Our findings indicate that previously reported emotional dampening associated with elevated BP extends to reduced involuntary emotional reactivity and to individuals with even minimal BP elevations (i.e. higher but still within the normal range). Future research needs to confirm these findings in hypertensive individuals, preferably using within-subjects designs.

Childhood maltreatment and its mental health consequences among Indian adolescents with a history of child work.

OBJECTIVES: Although the prevalence and mental health consequences of childhood maltreatment among adolescents have been studied widely, there are few data addressing these issues in Asian lower middle-income countries. Here, we assessed the prevalence and types of childhood maltreatment and, for the first time, examined their association with current mental health problems in Indian adolescents with a history of child work. METHODS: One hundred and thirty-two adolescents (12-18 years; 114 males, 18 females) with a history of child work were interviewed using the Child Maltreatment, Conventional Crime, and Witnessing and Indirect Victimisation modules of the Juvenile Victimization Questionnaire. Potential psychiatric diagnoses and current emotional and behavioural problems were assessed using the culturally adapted Hindi versions of the Youth's Inventory-4R and the Strengths and Difficulties Questionnaire, respectively. RESULTS: A large proportion of the sample reported childhood abuse or neglect (83.36%), direct or indirect victimisation (100%) and experienced symptoms of one or more psychiatric disorders (83.33%). Of the most common maltreatment types, physical abuse was present for 72.73% (extra-familial 56.25%, intra-familial 42.71%), emotional abuse for 47.7% (extra-familial 74.6%, intra-familial 12.9%), general neglect for 17.4% and unsafe home for 45.5% of the adolescents. All these maltreatment types were associated with poor mental health, with emotional abuse showing the strongest and wide-ranging impact. CONCLUSIONS: Indian adolescents with a history of child work are at an extremely high risk of extra-familial physical and emotional abuse as well as victimisation. They also experience a range of psychiatric symptoms, especially if they suffered emotional abuse. There is an urgent need for routine mental health screening and to consider emotional abuse in all current and future top-down and bottom-up approaches to address childhood maltreatment, as well as in potential interventions to ameliorate its adverse effects on mental health and well-being, of child and adolescent workers.

Entry of Polarized Effector Cells into Quiescence Forces HIV Latency.

The latent HIV reservoir is generated following HIV infection of activated effector CD4 T cells, which then transition to a memory phenotype. Here, we describe an ex vivo method, called QUECEL (quiescent effector cell latency), that mimics this process efficiently and allows production of large numbers of latently infected CD4+ T cells. Naïve CD4+ T cells were polarized into the four major T cell subsets (Th1, Th2, Th17, and Treg) and subsequently infected with a single-round reporter virus which expressed GFP/CD8a. The infected cells were purified and coerced into quiescence using a defined cocktail of cytokines, including tumor growth factor beta, interleukin-10 (IL-10), and IL-8, producing a homogeneous population of latently infected cells. Flow cytometry and transcriptome sequencing (RNA-Seq) demonstrated that the cells maintained the correct polarization phenotypes and had withdrawn from the cell cycle. Key pathways and gene sets enriched during transition from quiescence to reactivation include E2F targets, G2M checkpoint, estrogen response late gene expression, and c-myc targets. Reactivation of HIV by latency-reversing agents (LRAs) closely mimics RNA induction profiles seen in cells from well-suppressed HIV patient samples using the envelope detection of in vitro transcription sequencing (EDITS) assay. Since homogeneous populations of latently infected cells can be recovered, the QUECEL model has an excellent signal-to-noise ratio and has been extremely consistent and reproducible in numerous experiments performed during the last 4 years. The ease, efficiency, and accuracy of the mimicking of physiological conditions make the QUECEL model a robust and reproducible tool to study the molecular mechanisms underlying HIV latency.IMPORTANCE Current primary cell models for HIV latency correlate poorly with the reactivation behavior of patient cells. We have developed a new model, called QUECEL, which generates a large and homogenous population of latently infected CD4+ memory cells. By purifying HIV-infected cells and inducing cell quiescence with a defined cocktail of cytokines, we have eliminated the largest problems with previous primary cell models of HIV latency: variable infection levels, ill-defined polarization states, and inefficient shutdown of cellular transcription. Latency reversal in the QUECEL model by a wide range of agents correlates strongly with RNA induction in patient samples. This scalable and highly reproducible model of HIV latency will permit detailed analysis of cellular mechanisms controlling HIV latency and reactivation.

Complex Systems Biology Approach in Connecting PI3K-Akt and NF-κB Pathways in Prostate Cancer.

Phosphatidylinositol 3'-OH kinase (PI3K)-Akt and transcription factor NF-κB are important molecules involved in the regulation of cell proliferation, apoptosis, and oncogenesis. Both PI3K-Akt and Nuclear Factor-kappaB (NF-κB) are involved in the development and progression of prostate cancer, however, the crosstalk and molecules connecting these pathway remains unclear. A multilevel system representation of the PI3K-Akt and NF-κB pathways was constructed to determine which signaling components contribute to adaptive behavior and coordination. In silico experiments conducted using PI3K-Akt and NF-κB, mathematical models were modularized using biological functionality and were validated using a cell culture system. Our analysis demonstrates that a component representing the IκB kinase (IKK) complex can coordinate these two pathways. It is expected that interruption of this molecule could represent a potential therapeutic target for prostate cancer.