Age differences in the experience of everyday happiness: The role of thinking about the future.

Happiness can be experienced differently in young as compared to older adulthood, possibly due to shifts in temporal focus and differences in preferences for high- versus low-arousal affective states. The current project aimed to replicate initial evidence on age-related differences in the experience of happiness by investigating the positive affective correlates of everyday happiness; we further explored the role of thinking about the future in moderating such associations. We used daily life assessments from 257 participants (Mage = 48.3, SDage = 24.6; 68% female; 77% Asian [East Asian, South Asian, and Southeast Asian]; 73% postsecondary educated), combining four data sets collected at two locations (Vancouver, Canada; Hong Kong) with different age samples (older and younger adults). Participants provided up to 30 repeated daily life assessments of momentary affective states and thoughts about the future, over 10 days. Results replicate previous findings by showing that happiness was more strongly associated with low-arousal positive affect and more weakly associated with high-arousal positive affect among older compared to younger adults. Engagement in thinking about the future was higher among younger compared to older adults in general, but its role in moderating the association between happiness and positive affect varying in arousal levels was confounded by the age moderation. Separate analyses conducted for each age group indicate different roles of everyday thinking about the future in shaping happiness experiences for different age groups. Age and future thinking-related contours of happiness are discussed in the context of emotional aging theories. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Effects of different positive end-expiratory pressure titration strategies on mechanical power during ultraprotective ventilation in ARDS patients treated with veno-venous extracorporeal membrane oxygenation: A prospective interventional study.

PURPOSE: Ultraprotective ventilation in acute respiratory distress syndrome (ARDS) patients with veno-venous extracorporeal membrane oxygenation (VV ECMO) reduces mechanical power (MP) through changes in positive end-expiratory pressure (PEEP); however, the optimal approach to titrate PEEP is unknown. This study assesses the effects of three PEEP titration strategies on MP, hemodynamic parameters, and oxygen delivery in twenty ARDS patients with VV ECMO. MATERIAL AND METHODS: PEEP was titrated according to: (A) a PEEP of 10 cmH2O representing the lowest recommendation by the Extracorporeal Life Support Organization (PEEPELSO), (B) the highest static compliance of the respiratory system (PEEPCstat,RS), and (C) a target end-expiratory transpulmonary pressure of 0 cmH2O (PEEPPtpexp). RESULTS: PEEPELSO was lower compared to PEEPCstat,RS and PEEPPtpexp (10.0 ± 0.0 vs. 16.2 ± 4.7 cmH2O and 17.3 ± 4.0 cmH2O, p < 0.001 each, respectively). PEEPELSO reduced MP compared to PEEPCstat,RS and PEEPPtpexp (5.3 ± 1.3 vs. 6.8 ± 2.0 and 6.9 ± 2.3 J/min, p < 0.001 each, respectively). PEEPELSO resulted in less lung stress compared to PEEPCstat,RS (p = 0.011) and PEEPPtpexp (p < 0.001) and increased cardiac output and oxygen delivery (p < 0.001 each). CONCLUSIONS: An empirical PEEP of 10 cmH2O minimized MP, provided favorable hemodynamics, and increased oxygen delivery in ARDS patients treated with VV ECMO. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018https://drks.de/search/en/trial/DRKS00013967.

Everyday Pain in Middle and Later Life: Associations with Daily and Momentary Present-Moment Awareness as One Key Facet of Mindfulness.

This study investigated everyday associations between one key facet of mindfulness (allocating attention to the present moment) and pain. In Study 1, 89 community-dwelling adults (33-88 years; Mage = 68.6) who had experienced a stroke provided 14 daily end-of-day present-moment awareness and pain ratings. In Study 2, 100 adults (50-85 years; Mage = 67.0 years) provided momentary present-moment awareness and pain ratings three times daily for 10 days. Multi-level models showed that higher trait present-moment awareness was linked with lower overall pain (both studies). In Study 1, participants reported less pain on days on which they indicated higher present-moment awareness. In Study 2, only individuals with no post-secondary education reported less pain in moments when they indicated higher present-moment awareness. Findings add to previous research using global retrospective pain measures by showing that present-moment awareness might correlate with reduced pain experiences, assessed close in time to when they occur.

Effect of Exercise Training or Complex Mental and Social Activities on Cognitive Function in Adults With Chronic Stroke: A Randomized Clinical Trial.

Importance: A stroke doubles one's risk for dementia. How to promote cognitive function among persons with chronic stroke is unclear. Objective: To evaluate the effect of exercise (EX) or cognitive and social enrichment activities (ENRICH) on cognitive function in adults with chronic stroke. Design, Setting, and Participants: This was a 3-group parallel, single-blinded, single-site, proof-of-concept randomized clinical trial at a research center in Vancouver, British Columbia, Canada. Participants included community-dwelling adults with chronic stroke, aged 55 years and older, able to walk 6 meters, and without dementia. The trial included a 6-month intervention and a 6-month follow-up. Randomization occurred from June 6, 2014, to February 26, 2019. Measurement occurred at baseline, 6 months, and 12 months. Data were analyzed from January to November 2021. Interventions: Participants were randomly allocated to twice-weekly supervised classes of: (1) EX, a multicomponent exercise program; (2) ENRICH, a program of cognitive and social enrichment activities; or (3) balance and tone (BAT), a control group that included stretches and light-intensity exercises. Main Outcomes and Measures: The primary outcome was the Alzheimer Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus), which included the 13-item ADAS-Cog, Trail Making Test Parts A and B, Digit Span Forward and Backward, Animal Fluency, and Vegetable Fluency. Results: One-hundred and twenty participants, with a mean (range) of 1.2 (1-4) strokes, a mean (SD) of 66.5 (53.8) months since the most recent stroke, mean (SD) baseline age of 70 (8) years, mean (SD) baseline ADAS-Cog-Plus of 0.22 (0.81), and 74 (62%) male participants, were randomized to EX (34 participants), ENRICH (34 participants), or BAT (52 participants). Seventeen withdrew during the 6-month intervention and another 7 during the 6-month follow-up. Including all 120 participants, at the end of the 6-month intervention, EX significantly improved ADAS-Cog-Plus performance compared with BAT (estimated mean difference: -0.24; 95% CI, -0.43 to -0.04; P = .02). This difference did not persist at the 6-month follow-up (estimated mean difference: -0.08; 95% CI, -0.29 to 0.12; P = .43). For the 13-item ADAS-Cog, the EX group improved by 5.65 points over the 6-month intervention (95% CI, 2.74 to 8.57 points; P < .001), exceeding the minimally clinical difference of 3.0 points. Conclusions and Relevance: These findings suggest that exercise can induce clinically important improvements in cognitive function in adults with chronic stroke. Future studies need to replicate current findings and to understand training parameters, moderators, and mediators to maximize benefits. Trial Registration: ClinicalTrials.gov identifier: NCT01916486.

Small-world complex network generation on a digital quantum processor.

Quantum cellular automata (QCA) evolve qubits in a quantum circuit depending only on the states of their neighborhoods and model how rich physical complexity can emerge from a simple set of underlying dynamical rules. The inability of classical computers to simulate large quantum systems hinders the elucidation of quantum cellular automata, but quantum computers offer an ideal simulation platform. Here, we experimentally realize QCA on a digital quantum processor, simulating a one-dimensional Goldilocks rule on chains of up to 23 superconducting qubits. We calculate calibrated and error-mitigated population dynamics and complex network measures, which indicate the formation of small-world mutual information networks. These networks decohere at fixed circuit depth independent of system size, the largest of which corresponding to 1,056 two-qubit gates. Such computations may enable the employment of QCA in applications like the simulation of strongly-correlated matter or beyond-classical computational demonstrations.

The differential roles of chronic and transient loneliness in daily prosocial behavior.

Loneliness is a recognized risk factor for morbidity and mortality across the adult life span including old age. Loneliness is a negative emotional experience that has been associated with social isolation, but loneliness may also be adaptive to the extent that it signals a need to socially reengage. To reconcile these seemingly contradictory findings, we unpack the timing of the underlying processes by distinguishing between transient and chronic loneliness in shaping prosocial behaviors. Using 10 days of electronic daily life assessments from 100 middle-aged and older adults (Mage = 67.0 years; 64.0% women), findings indicate that chronic loneliness moderates time-varying associations between transient loneliness and prosocial behavior. Simple slope results point to individual differences in daily loneliness-prosocial action associations. Specifically, adults high in chronic loneliness, but not those low in chronic loneliness, showed decreased prosocial behaviors on days with elevated transient loneliness. Findings suggest that chronic loneliness may elicit maladaptive responses to transient loneliness by hampering the use of opportunities to engage in prosocial behavior. Exploratory analyses point to fear of evaluation as a potential mechanism that is associated with increased loneliness and reduced prosocial behavior. Findings highlight the differential roles of transient and chronic loneliness in shaping prosocial activities in midlife and older adulthood, thereby providing a more nuanced picture as well as potential avenues for intervention. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Ultraprotective versus apneic ventilation in acute respiratory distress syndrome patients with extracorporeal membrane oxygenation: a physiological study.

BACKGROUND: Even an ultraprotective ventilation strategy in severe acute respiratory distress syndrome (ARDS) patients treated with extracorporeal membrane oxygenation (ECMO) might induce ventilator-induced lung injury and apneic ventilation with the sole application of positive end-expiratory pressure may, therefore, be an alternative ventilation strategy. We, therefore, compared the effects of ultraprotective ventilation with apneic ventilation on oxygenation, oxygen delivery, respiratory system mechanics, hemodynamics, strain, air distribution and recruitment of the lung parenchyma in ARDS patients with ECMO. METHODS: In a prospective, monocentric physiological study, 24 patients with severe ARDS managed with ECMO were ventilated using ultraprotective ventilation (tidal volume 3 ml/kg of predicted body weight) with a fraction of inspired oxygen (FiO2) of 21%, 50% and 90%. Patients were then treated with apneic ventilation with analogous FiO2. The primary endpoint was the effect of the ventilation strategy on oxygenation and oxygen delivery. The secondary endpoints were mechanical power, stress, regional air distribution, lung recruitment and the resulting strain, evaluated by chest computed tomography, associated with the application of PEEP (apneic ventilation) and/or low VT (ultraprotective ventilation). RESULTS: Protective ventilation, compared to apneic ventilation, improved oxygenation (arterial partial pressure of oxygen, p < 0.001 with FiO2 of 50% and 90%) and reduced cardiac output. Both ventilation strategies preserved oxygen delivery independent of the FiO2. Protective ventilation increased driving pressure, stress, strain, mechanical power, as well as induced additional recruitment in the non-dependent lung compared to apneic ventilation. CONCLUSIONS: In patients with severe ARDS managed with ECMO, ultraprotective ventilation compared to apneic ventilation improved oxygenation, but increased stress, strain, and mechanical power. Apneic ventilation might be considered as one of the options in the initial phase of ECMO treatment in severe ARDS patients to facilitate lung rest and prevent ventilator-induced lung injury. TRIAL REGISTRATION: German Clinical Trials Register (DRKS00013967). Registered 02/09/2018. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00013967 .

Effects of different positive end-expiratory pressure titration strategies during prone positioning in patients with acute respiratory distress syndrome: a prospective interventional study.

BACKGROUND: Prone positioning in combination with the application of low tidal volume and adequate positive end-expiratory pressure (PEEP) improves survival in patients with moderate to severe acute respiratory distress syndrome (ARDS). However, the effects of PEEP on end-expiratory transpulmonary pressure (Ptpexp) during prone positioning require clarification. For this purpose, the effects of three different PEEP titration strategies on Ptpexp, respiratory mechanics, mechanical power, gas exchange, and hemodynamics were evaluated comparing supine and prone positioning. METHODS: In forty consecutive patients with moderate to severe ARDS protective ventilation with PEEP titrated according to three different titration strategies was evaluated during supine and prone positioning: (A) ARDS Network recommendations (PEEPARDSNetwork), (B) the lowest static elastance of the respiratory system (PEEPEstat,RS), and (C) targeting a positive Ptpexp (PEEPPtpexp). The primary endpoint was to analyze whether Ptpexp differed significantly according to PEEP titration strategy during supine and prone positioning. RESULTS: Ptpexp increased progressively with prone positioning compared with supine positioning as well as with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork (positioning effect p < 0.001, PEEP strategy effect p < 0.001). PEEP was lower during prone positioning with PEEPEstat,RS and PEEPPtpexp (positioning effect p < 0.001, PEEP strategy effect p < 0.001). During supine positioning, mechanical power increased progressively with PEEPEstat,RS and PEEPPtpexp compared with PEEPARDSNetwork, and prone positioning attenuated this effect (positioning effect p < 0.001, PEEP strategy effect p < 0.001). Prone compared with supine positioning significantly improved oxygenation (positioning effect p < 0.001, PEEP strategy effect p < 0.001) while hemodynamics remained stable in both positions. CONCLUSIONS: Prone positioning increased transpulmonary pressures while improving oxygenation and hemodynamics in patients with moderate to severe ARDS when PEEP was titrated according to the ARDS Network lower PEEP table. This PEEP titration strategy minimized parameters associated with ventilator-induced lung injury induction, such as transpulmonary driving pressure and mechanical power. We propose that a lower PEEP strategy (PEEPARDSNetwork) in combination with prone positioning may be part of a lung protective ventilation strategy in patients with moderate to severe ARDS. TRIAL REGISTRATION: German Clinical Trials Register ( DRKS00017449 ). Registered June 27, 2019. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00017449.

Procollagen I and III as Prognostic Markers in Patients Treated with Extracorporeal Membrane Oxygenation: A Prospective Observational Study.

Background: Procollagen peptides have been associated with lung fibroproliferation and poor outcomes in patients with acute respiratory distress syndrome (ARDS). Therefore, serum procollagen concentrations might have prognostic value in ARDS patients treated with extracorporeal membrane oxygenation (ECMO). Methods: In a prospective cohort study, serum N-terminal procollagen I-peptide (PINP) and N-terminal procollagen III-peptide (PIIINP) concentrations in twenty-three consecutive patients with severe ARDS treated with ECMO were measured at the time of ECMO initiation and during the course of treatment. The predictive value of PINP and PIIINP at the time of ECMO initiation was tested with a univariable logistic regression and a receiver operating characteristic (ROC) curve analysis. Results: Thirteen patients survived to intensive care unit (ICU) discharge. Non-survivors had higher serum PINP and PIIINP concentrations at all points in time during the course of treatment. Serum PIIINP at the day of ECMO initiation showed an odds ratio of 1.37 (95% CI 1.10-1.89, p = 0.017) with an area under the receiver operating characteristic (ROC) curve (AUC) of 0.87 (95% CI 0.69-1.00, p = 0.0029) for death during the course of treatment. Conclusions: PINP and PIIINP concentrations differ between survivors and non-survivors in ARDS treated with ECMO. This exploratory hypothesis generating study suggests an association between PIIINP serum concentrations at ECMO initiation and an unfavorable clinical outcome.

The BH3 mimetic (±) gossypol induces ROS-independent apoptosis and mitochondrial dysfunction in human A375 melanoma cells in vitro.

A major challenge in current cancer therapy is still the treatment of metastatic melanomas of the skin. BH3 mimetics represent a novel group of substances inducing apoptosis. In this study, we investigated the cytotoxic effect of (±) gossypol (GP), a natural compound from cotton seed, on A375 melanoma cells and the underlying biochemical mechanisms. To prevent undesired side effects due to toxicity on normal (healthy) cells, concentrations only toxic for tumor cells have been elaborated. Viability assays were performed to determine the cytotoxicity of GP in A375 melanoma and normal (healthy) cells. For the majority of experiments, a concentration of 2.5 µM GP was used resulting in a ROS-independent but caspase-dependent cell death of A375 melanoma cells. At this level, GP was non-toxic for normal human epidermal melanocytes. GP has a very short half-life, however, it was demonstrated that only the "parent" compound and not decomposition products are responsible for the cytotoxic effect in A375 melanoma cells. GP significantly decreased mitochondrial membrane potential accompanied by a Drp1-dependent loss of mitochondrial integrity (fragmentation) in tumor cells. Taken together, GP induced a ROS-independent intrinsic apoptosis leading to the conclusion that within a specific concentration range, GP may work as effective anticancer drug without harmful side effects.

Retrieval-induced forgetting in a social task.

Clinical researchers suggest that post-event thinking functions to negatively bias event recall for socially anxious participants. We used a repeated retrieval paradigm to examine the effects of post-event retrieval on memory for social information. Undergraduate participants (n = 214) engaged in an impromptu public speaking task and received a standardised mixture of positive and negative feedback on their speech. Participants in the experimental condition were instructed to repeatedly retrieve the negative feedback items whereas participants in the control condition completed a control task. Both groups were asked to recall the feedback after five minutes and after one week. Results indicated that the experimental group displayed the hypothesised retrieval-induced forgetting effect. In addition, repeated retrieval predicted valence change in that participants recalled the non-retrieved positive feedback items less positively over time. The retrieval-practice effects were distinct from self-reported post-event processing. Contrary to clinical theories, social anxiety did not moderate retrieval-induced forgetting or recall bias. Instead, all participants displayed retrieval-related negatively biased recall.

Matching crystal structures atom-to-atom.

Finding an optimal match between two different crystal structures underpins many important materials science problems, including describing solid-solid phase transitions and developing models for interface and grain boundary structures. In this work, we formulate the matching of crystals as an optimization problem where the goal is to find the alignment and the atom-to-atom map that minimize a given cost function such as the Euclidean distance between the atoms. We construct an algorithm that directly solves this problem for large finite portions of the crystals and retrieves the periodicity of the match subsequently. We demonstrate its capacity to describe transformation pathways between known polymorphs and to reproduce experimentally realized structures of semi-coherent interfaces. Additionally, from our findings, we define a rigorous metric for measuring distances between crystal structures that can be used to properly quantify their geometric (Euclidean) closeness.

Choosing Solitude: Age Differences in Situational and Affective Correlates of Solitude-Seeking in Midlife and Older Adulthood.

OBJECTIVES: Despite a basic need for social connection, individuals across the adult lifespan sometimes seek solitude-a phenomenon that is not well understood. This study examined situational and affective correlates of solitude-seeking and how they may differ between middle-aged and older adults. METHOD: One hundred community-dwelling adults aged 50-85 years (64% female, 56% East Asian, 36% European, 8% other) completed approximately 30 electronic daily life assessments over 10 days regarding their current location, affect, activities, and current and desired social context. RESULTS: Solitude was common; 86% of solitude instances happened by individuals' own choosing. When desiring solitude, older adults were more likely to be at home and less likely to be outdoors, compared to other locations. Middle-aged adults showed no such solitude-location associations. Among middle-aged adults, desire for solitude was associated with decreased positive affect. Older adults experienced no such dip in affect. DISCUSSION: Findings suggest that compared to middle-aged adults, older adults are more likely to go to locations that match their desired social context, and also that solitude-seeking has more positive ramifications for older adults. Findings are discussed in the context of age differences in activities, social preferences, and emotion regulation.

Solitude in context: On the role of culture, immigration, and acculturation in the experience of time to oneself.

Older adults spend much time in solitude (without social interaction), putting them at risk of loneliness, especially if aging outside their country of origin (e.g., Chinese immigrants to Canada). Yet, cultural contextual factors that may reduce loneliness in moments of solitude are poorly understood. This study sought to disentangle the roles of culture, immigration, and acculturation in solitude-loneliness associations across two countries. Community-dwelling adults aged 51-85 in Vancouver (N = 58 East Asian, N = 37 European/North American) and in Hong Kong (N = 56 East/Southeast Asian) completed approximately 30 ecological momentary assessments over 10 days on their current affect and social situations. Participants in Vancouver spent more time in solitude, desired solitude more, and felt less lonely overall than those in Hong Kong. Multilevel models revealed that moments of solitude felt lonelier than moments spent in social interaction, but only for individuals less acculturated to their host culture or not concurrently desiring solitude. Associations held regardless of host culture, cultural heritage, or immigration status. Findings suggest that solitude need not feel lonely if it happens by choice and if individuals feel connected with their host culture, for both immigrant older adults and those aging in their birth country.

Everyday solitude, affective experiences, and well-being in old age: the role of culture versus immigration.

Objectives: Being alone is often equated with loneliness. Yet, recent findings suggest that the objective state of being alone (i.e. solitude) can have both positive and negative connotations. The present research aimed to examine (1) affective experience in daily solitude; and (2) the association between everyday affect in solitude and well-being. We examined the distinct roles of culture and immigration in moderating these associations. Method: Using up to 35 daily life assessments of momentary affect, solitude, and emotional well-being in two samples (Canada and China), the study compared older adults who aged in place (local Caucasians in Vancouver , Canada and local Hong Kong Chinese in Hong Kong, China) and older adults of different cultural heritages who immigrated to Canada (immigrated Caucasians and immigrated East Asians). Results: We found that older adults of East Asian heritage experienced more positive and less negative affect when alone than did Caucasians. Reporting positive affect in solitude was more positively associated with well-being in older adults who had immigrated to Canada as compared to those who had aged in place. Conclusions:These findings speak to the unique effects of culture and immigration on the affective correlates of solitude and their associations with well-being in old age.

By myself and liking it? Predictors of distinct types of solitude experiences in daily life.

OBJECTIVE: Solitude is a ubiquitous experience, often confused with loneliness, yet sometimes sought out in daily life. This study aimed to identify distinct types of solitude experiences from everyday affect/thought patterns and to examine how and for whom solitude is experienced positively versus negatively. METHOD: One hundred community-dwelling adults aged 50-85 years (64% female; 56% East Asian, 36% European, 8% other/mixed heritage) and 50 students aged 18-28 years (92% female; 42% East Asian, 22% European, 36% other/mixed) each completed approximately 30 daily life assessments over 10 days on their current and desired social situation, thoughts, and affect. RESULTS: Multilevel latent profile analysis identified two types of everyday solitude: one characterized by negative affect and effortful thought (negative solitude experiences) and one characterized by calm and the near absence of negative affect/effortful thought (positive solitude experiences). Individual differences in social self-efficacy and desire for solitude were associated with everyday positive solitude propensity; trait self-rumination and self-reflection were associated with everyday negative solitude propensity. CONCLUSIONS: This study provides a new framework for conceptualizing everyday solitude. It identifies specific affect/thought patterns that characterize distinct solitude experience clusters, and it links these clusters with well-established individual differences. We discuss key traits associated with thriving in solitude.

Study protocol for Vitality: a proof-of-concept randomised controlled trial of exercise training or complex mental and social activities to promote cognition in adults with chronic stroke.

INTRODUCTION: Cerebrovascular disease-such as stroke-is the second most common cause of dementia (ie, vascular dementia). Specifically, a stroke increases one's risk for dementia by a factor of two. Thus, stroke survivors represent a target population in need of intervention strategies to promote cognitive function and prevent dementia. The current standard of care in stroke rehabilitation does not adequately address the significant cognitive consequences of stroke, especially for those who are in the chronic phase (ie, >12 months since an index stroke). Two potential intervention strategies are: (1) exercise training and (2) cognitive and social enrichment activities. METHODS AND ANALYSIS: The aim of this proof-of-concept randomised controlled trial is to determine whether a 6-month targeted exercise training programme or a 6-month cognitive and social enrichment programme can efficaciously and efficiently improve cognitive function in older adults with chronic stroke compared with a 6-month stretch and tone programme (ie, control). The primary measurement periods will be baseline, month 6 (postintervention) and month 12 (6-month follow-up). The primary outcome measure will be performance on the Alzheimer's Disease Assessment Scale-Cognitive-Plus (ADAS-Cog-Plus), a global measure of cognitive performance using multidimensional item response theory to summarise scores from the 13-item ADAS-Cog and other standard cognitive assessments. The primary analysis will compare changes in ADAS-Cog-Plus performance from baseline to month 6. Proof-of-concept outcomes relating to intervention feasibility will be analysed descriptively. The economic evaluation will examine the incremental costs and health outcome benefits generated by both interventions versus the control. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the University of British Columbia's Clinical Research Ethics Board (H13-00715, 26 July 2013). Any modifications to the protocol will require a formal amendment to the protocol and approval by the Research Ethics Board. Outcomes of this randomised controlled trial and the statistical code to generate those outcomes will be disseminated through publication in peer-reviewed journals as well as conference presentations. TRIAL REGISTRATION NUMBER: NCT01916486.

APC/C-Cdc20 mediates deprotection of centromeric cohesin at meiosis II in yeast.

Cells undergoing meiosis produce haploid gametes through one round of DNA replication followed by 2 rounds of chromosome segregation. This requires that cohesin complexes, which establish sister chromatid cohesion during S phase, are removed in a stepwise manner. At meiosis I, the separase protease triggers the segregation of homologous chromosomes by cleaving cohesin's Rec8 subunit on chromosome arms. Cohesin persists at centromeres because the PP2A phosphatase, recruited by the shugoshin protein, dephosphorylates Rec8 and thereby protects it from cleavage. While chromatids disjoin upon cleavage of centromeric Rec8 at meiosis II, it was unclear how and when centromeric Rec8 is liberated from its protector PP2A. One proposal is that bipolar spindle forces separate PP2A from Rec8 as cells enter metaphase II. We show here that sister centromere biorientation is not sufficient to "deprotect" Rec8 at meiosis II in yeast. Instead, our data suggest that the ubiquitin-ligase APC/CCdc20 removes PP2A from centromeres by targeting for degradation the shugoshin Sgo1 and the kinase Mps1. This implies that Rec8 remains protected until entry into anaphase II when it is phosphorylated concurrently with the activation of separase. Here, we provide further support for this model and speculate on its relevance to mammalian oocytes.

Casein Kinase 1 Coordinates Cohesin Cleavage, Gametogenesis, and Exit from M Phase in Meiosis II.

Meiosis consists of DNA replication followed by two consecutive nuclear divisions and gametogenesis or spore formation. While meiosis I has been studied extensively, less is known about the regulation of meiosis II. Here we show that Hrr25, the conserved casein kinase 1δ of budding yeast, links three mutually independent key processes of meiosis II. First, Hrr25 induces nuclear division by priming centromeric cohesin for cleavage by separase. Hrr25 simultaneously phosphorylates Rec8, the cleavable subunit of cohesin, and removes from centromeres the cohesin protector composed of shugoshin and the phosphatase PP2A. Second, Hrr25 initiates the sporulation program by inducing the synthesis of membranes that engulf the emerging nuclei at anaphase II. Third, Hrr25 mediates exit from meiosis II by activating pathways that trigger the destruction of M-phase-promoting kinases. Thus, Hrr25 synchronizes formation of the single-copy genome with gamete differentiation and termination of meiosis.