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Three studies describe the development and refinement of a measure designed to assess Attitudes TowardWorking Single Parents (AWSP). Study 1 consisted of content validation of items written to assess respondent attitudes regarding the effect of single parenthood on two dimensions viewed as most central to the life experiences of single parents: work and family. Study 2 involved exploratory factor analysis and reliability analysis of the scores on the target measure. Finally, in Study 3, a confirmatory factor analysis was conducted to evaluate scale dimensionality, and discriminant, convergent, and subgroup validity coefficients were examined. The final scale may prove useful in guiding future research aimed at understanding the unique challenges faced byworking single parents. [ABSTRACT FROM AUTHOR]

The aim of this research was to explore relations between work resources (supervisory support and organizational family supportive values), work-to-family conflict (WFC), and work- and nonwork-related outcomes in a cross-cultural comparative context involving Taiwanese and British employees. The authors surveyed 264 Taiwanese employees and 137 British employees using structured questionnaires. For both Taiwanese and British employees, work resources were found to be negatively related to WFC but positively related to work satisfaction. WFC was negatively related to work and/or family satisfaction. More important, the authors found that nation moderated the relationship between supervisory support and WFC: Supervisory support had a stronger protective effect for Taiwanese than British employees. It is thus recommended that, in addition to introducing various family-friendly policies, companies should be more active in cultivating a family-supportive organizational culture and mobilizing managers to act as supporters of family life, especially in societies sanctioning collectivistic values and large power distance. [ABSTRACT FROM AUTHOR]

Little empirical research exists on attributions that people make regarding work-family conflict that they experience. Our study used attribution theory to examine the aftermath of work-family conflict episodes. We used a diary method in which respondents reported their daily encounters with work-family conflict, attributions they made about its causes, feelings of guilt and shame they experienced, and their levels of daily family engagement and well-being after work. Based on Ilies et al. (2012) we hypothesized that internal attributions of work-family conflict would be associated with feelings of guilt and shame, and that these emotions would in turn be differentially associated with daily after-work outcomes. We also hypothesized that the degree to which individuals were satisfied with the resolution of their work-family conflict would moderate the relationship between internal attribution and guilt/shame. Results largely supported our hypotheses, with guilt demonstrating a positive link to family engagement while shame showed a negative association. We also found that shame, but not guilt, was negatively associated with daily well-being. One's level of satisfaction with the resolution of work-family conflict emerged as a key variable as well. Lastly, we discuss the theoretical and practical ramifications of our findings., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The mitotic regulator, Aurora kinase B (AURKB), is frequently overexpressed in malignancy and is a target for therapeutic intervention. The compound, LXY18, is a potent, orally available small molecule that inhibits the proper localization of AURKB during late mitosis, without affecting its kinase activity. In this study, we demonstrate that LXY18 elicits apoptosis in cancer cells derived from various indications, but not in non-transformed cell lines. The apoptosis is p53-independent, triggered by a prolonged mitotic arrest and occurs predominantly in mitosis. Some additional cells succumb post-mitotic slippage. We also demonstrate that cancer cell lines refractory to AURKB kinase inhibitors are sensitive to LXY18. The mitotic proteins MKLP2, NEK6, NEK7 and NEK9 are known regulators of AURKB localization during the onset of anaphase. LXY18 fails to inhibit the catalytic activity of these AURKB localization factors. Overall, our findings suggest a novel activity for LXY18 that produces a prolonged mitotic arrest and lethality in cancer cells, leaving non-transformed cells healthy. This new activity suggests that the compound may be a promising drug candidate for cancer treatment and that it can also be used as a tool compound to further dissect the regulatory network controlling AURKB localization., Competing Interests: The J. Michael Bishop Institute of Cancer Research and Chengdu Anticancer Bioscience LTD has filed a PCT application (PCT/CN2021/82684) that covers the compound LXY18 under this study. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2023 Kalashova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Although cross-national work-family research has made great strides in recent decades, knowledge accumulation on the impact of culture on the work-family interface has been hampered by a limited geographical and cultural scope that has excluded countries where cultural expectations regarding work, family, and support may differ. We advance this literature by investigating work-family relationships in a broad range of cultures, including understudied regions of the world (i.e., Sub-Saharan Africa, Southern Asia). We focus on humane orientation (HO), an overlooked cultural dimension that is however central to the study of social support and higher in those regions. We explore its moderating effect on relationships between work and family social support, work-family conflict, and work-family positive spillover. Building on the congruence and compensation perspectives of fit theory, we test alternative hypotheses on a sample of 10,307 participants from 30 countries/territories. We find HO has mostly a compensatory role in the relationships between workplace support and work-to-family conflict. Specifically, supervisor and coworker supports were most strongly and negatively related to conflict in cultures in which support is most needed (i.e., lower HO cultures). Regarding positive spillover, HO has mostly an amplifying role. Coworker (but not supervisor) support was most strongly and positively related to work-to-family positive spillover in higher HO cultures, where providing social support at work is consistent with the societal practice of providing support to one another. Likewise, instrumental (but not emotional) family support was most strongly and positively related to family-to-work positive spillover in higher HO cultures. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

This study investigated the metabolism of LXY18, a quinolone-based compound that suppresses tumorigenesis by blocking AURKB localization. Metabolite profiling of LXY18 in liver microsomes from six species and human S9 fractions revealed that LXY18 undergoes various conserved metabolic reactions, such as N-hydroxylation, N-oxygenation, O-dealkylation, and hydrolysis, resulting in ten metabolites. These metabolites were produced through a combination of CYP450 enzymes, and non-CYP450 enzymes including CES1, and AO. Two metabolites, M1 and M2 were authenticated by chemically synthesized standards. M1 was the hydrolyzed product catalyzed by CES1 whereas M2 was a mono-N-oxidative derivative catalyzed by a CYP450 enzyme. AO was identified as the enzyme responsible for the formation of M3 with the help of AO-specific inhibitors and LXY18 analogs, 5b and 5c. M1 was the intermediate of LXY18 to produce M7, M8, M9, and M10. LXY18 potently inhibited 2C19 with an IC 50 of 290 nM but had a negligible impact on the other CYP450s, indicating a low risk of drug-drug interaction. Altogether, the study provides valuable insights into the metabolic process of LXY18 and its suitability as a drug candidate. The data generated serves as a significant reference point for conducting further safety assessments and optimizing drug development., Competing Interests: Declaration of Competing Interest The authors declare the following competing financial interest. Anticancer Bioscience has submitted intellectual property filings (PCT/CN2021/091425 and PCT/CN2021/127309) that cover compounds described in this study., (Copyright © 2023 Elsevier B.V. All rights reserved.)

We investigated a novel 4-phenoxy-quinoline-based scaffold that mislocalizes the essential mitotic kinase, Aurora kinase B (AURKB). Here, we evaluated the impact of halogen substitutions (F, Cl, Br, and I) on this scaffold with respect to various drug parameters. Br-substituted LXY18 was found to be a potent and orally bioavailable disruptor of cell division, at sub-nanomolar concentrations. LXY18 prevents cytokinesis by blocking AURKB relocalization in mitosis and exhibits broad-spectrum antimitotic activity in vitro. With a favorable pharmacokinetic profile, it shows widespread tissue distribution including the blood-brain barrier penetrance and effective accumulation in tumor tissues. More importantly, it markedly suppresses tumor growth. The novel mode of action of LXY18 may eliminate some drawbacks of direct catalytic inhibition of Aurora kinases. Successful development of LXY18 as a clinical candidate for cancer treatment could enable a new, less toxic means of antimitotic attack that avoids drug resistance mechanisms., Competing Interests: The authors declare the following competing financial interest(s): Anticancer Bioscience has submitted intellectual property filings (PCT/CN2021/091425 and PCT/CN2021/127309) that cover compounds described in this study. Dr. D.Y. and J.Z. are stockholders of Anticancer Bioscience., (© 2023 American Chemical Society.)

The relationship between masculinity contest culture (MCC) and emotional exhaustion was examined with hypotheses informed by the job demands-resources model. Additionally, trait competitiveness and gender were considered as predictors within a three-way interaction model informed by social role theory. Hypotheses were tested using a two-timepoint survey with a sample of 494 full-time employed adults. Results indicate MCC relates to emotional exhaustion. Support is also provided for a three-way interaction between overall MCC, trait competitiveness, and gender with men with lower trait competitiveness displaying the strongest positive relationship. Overall, results suggest MCC operates as a stressor with the potential to harm psychological well-being and that the strength of this relationship varied based on gender and trait competitiveness. Specifically, higher trait competitiveness buffered relationships between MCC and exhaustion for men but intensified this relationship for women. Implications for employee well-being and disparate health outcomes across groups are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Over the past several decades, there has been considerable interest in the theoretical causes of work-family conflict (WFC). Most studies have focused on situational determinants, often ignoring the role of personal factors such as disposition and heritable elements. We increase understanding of person versus situation influences on WFC through estimation of the relationship between role demands and WFC after controlling for genetic confounding, measured personality traits, family confounds, and other stable dispositions. Based on twin data from the National Survey of Midlife Development in the United States (MIDUS), we examine the role of genetic factors in explaining variation in WFC (both work interference with family [WIF] and family interference with work [FIW]). Results support WFC has an additive genetic component, accounting for 31% [95% CI 18%, 45%] and 16% [95% CI 2%, 30%] of the variance in WIF and FIW, respectively. In addition, we test two competing hypotheses with regard to the relationship between role demands and WFC. Results support the phenotypic causal relationship for WIF, consistent with the notion the relationship between work demands and WIF reflect situational processes. However, results support the genetic confounding hypothesis for FIW, indicating observed relationships between family demands and FIW are primarily due to genetic factors. Our results provide new insights into the nature of WFC relationships and underscore that ignoring the influence of heritability can bias estimates of role demand effects in WFC research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

We combined a mechanism-informed phenotypic screening (MIPS) assay with a structural simplification strategy to guide the discovery of compounds that disrupt the localization of the mitotic regulator, Aurora kinase B (AURKB), rather than inhibiting its catalytic activity. An initial hit 4-(4-methylthiophen-2-yl)-N-(4-(quinolin-4-yloxy)phenyl)phthalazin-1-amine was identified after screening an in-house library of small molecules and phenocopied the loss of function mutations in AURKB without inhibiting its catalytic activity. We isolated this hit compound activity to its 4-phenoxy-quinoline moiety. The fragment was further optimized into a class of new chemical entities that potently disrupt the mitotic localization of AURKB at low nanomolar concentrations and consequently elicit severe growth inhibition in diverse human cancer cell lines. A lead compound, N-(3-methoxy-5-(6-methoxyquinolin-4-yl)oxy)phenyl)acetamide possessed desirable pharmacokinetic properties such as AUC 0-∞ : 227.15 [ng∙h/mL/(mg/kg)]; C max : 3378.52 ng/mL T 1/2 : 3.52 h; and F%: 42 % and produced the AURKB-inhibitory phenotypes in a mouse xenograft model. A lead compound is a powerful tool for interrogating the regulation of AURKB and has the potential to be further developed as a first-in-class oncology therapeutic., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: DUN YANG reports financial support was provided by Chengdu Anticancer Bioscience and J. Michael Bishop Institute of Cancer Research, Chengdu 610000, China. DUN YANG reports a relationship with Chengdu Anticancer Bioscience and J. Michael Bishop Institute of Cancer Research, Chengdu 610000, China that includes: employment and funding grants. DUN YANG has patent #PCT/CN2021/091425 and PCT/CN2021/127309 pending to Chengdu Anticancer Bioscience Ltd. The authors declare the following competing financial interest. Anticancer Bioscience has submitted PCT patent filing applications (PCT/CN2021/091425 and PCT/CN2021/127309) that cover compounds described in this study., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

The COVID-19 pandemic threatened employees' health and safety more than any event in recent years. Although millions of employees transitioned to working from home to mitigate infectious disease exposure, many worksites re-opened amid the pandemic as high infection rates persisted longer than expected. Safety guidelines were issued by the Centers for Disease Control and Prevention, the World Health Organization, and other national initiatives to improve the health and safety of employees returning to on-site work. The current work addresses predictors of infection control safety behaviors in a general working population that largely lacks infection control training and expertise. Drawing from Neal and Griffin's model of safety behavior, we investigated organizational factors (i.e., perceived safety climate, safety-related organizational constraints, occupational risk of COVID-19 exposure) and individual factors (i.e., infection control safety attitudes, conscientiousness, and risk aversion) associated with employees' infection control safety behaviors shortly after returning to on-site work during the pandemic. Survey results from 89 full-time employees across industries demonstrated that the organizational and individual factors accounted for 51.19 percent of the variance in employees' infection control safety behaviors. Organizational factors accounted for 49.02 percent of the explained variance, and individual factors accounted for 50.98 percent of the explained variance. Conscientiousness, perceived safety climate, safety-related organizational constraints, and infection control safety attitudes explained significant variance in employees' infection control safety behaviors, while the occupational risk of COVID-19 exposure and risk aversion did not. Organizations may benefit from considering employees' conscientiousness and safety attitudes during employee selection as well as enhancing their organization's safety climate and mitigating safety-related organizational constraints., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 Elsevier Ltd. All rights reserved.)

Objectives: It has been reported that job demands affect sleep, but how different levels of job demands affect sleep remains unclear. We examined whether curvilinear relationships exist between job demands and multiple sleep health outcomes., Design: Cross-sectional analyses with linear and quadratic effects, using self-administered survey data., Setting: A national sample of US adults., Participants: Workers from Midlife in the United States Study (MIDUS2; n = 2927)., Measurements: The Job Content Questionnaire assessed overall and 5 specific aspects of job demands (intensity, role conflict, work overload, time pressure, and interruptions). Habitual sleep health patterns across 5 dimensions (regularity, satisfaction/quality, daytime alertness, efficiency, and duration) were assessed. Age, sex, race/ethnicity, marital/partnered status, education, job tenure, work hours, body mass index, smoking status, and study sample were covariates., Results: There were significant linear and quadratic relationships between job demands and sleep outcomes. Specifically, the linear effects indicated that participants with higher job demands had worse sleep health, such as shorter duration, greater irregularity, greater inefficiency, and more sleep dissatisfaction. The quadratic effects, however, indicated that sleep regularity and efficiency outcomes were the best when participants' job demands were moderate rather than too low or too high. These effects were found for overall job demands as well as for specific aspects of job demands. Stratified analyses further revealed that these curvilinear associations were mainly driven by participants with low job control., Conclusions: Moderate levels of job demands, especially if combined with adequate job control, are related to optimal sleep health., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Plants are a rich source for bioactive compounds. However, plant extracts can harbor a mixture of bioactive molecules that promote divergent phenotypes and potentially have confounding effects in bioassays. Even with further purification and identification, target deconvolution can be challenging. Corynoline and acetylcorynoline, are phytochemicals that were previously isolated through a screen for compounds able to induce mitotic arrest and polyploidy in oncogene expressing retinal pigment epithelial (RPE) cells. Here, we shed light on the mechanism by which these phytochemicals can attack human cancer cells. Mitotic arrest was coincident to the induction of centrosome amplification and declustering, causing multi-polar spindle formation. Corynoline was demonstrated to have true centrosome declustering activity in a model where A549 cells were chemically induced to have more than a regular complement of centrosomes. Corynoline could inhibit the centrosome clustering required for pseudo-bipolar spindle formation in these cells. The activity of AURKB, but not AURKA or polo-like kinase 4, was diminished by corynoline. It only partially inhibited AURKB, so it may be a partial antagonist or corynoline may work upstream on an unknown regulator of AURKB activity or localization. Nonetheless, corynoline and acetylcorynoline inhibited the viability of a variety of human cancer derived cell lines. These phytochemicals could serve as prototypes for a next-generation analog with improved potency, selectivity or in vivo bioavailability. Such an analog could be useful as a non-toxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired., (Copyright © 2022 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

National reports widely publicized that the coronavirus disease (COVID-19) pandemic's disruption of work-nonwork boundaries impacted women's careers negatively, as many exited their jobs to manage nonwork demands. We know less about the adaptations made by highly career-invested women to remain in the workforce in occupations where they are extremely under-represented. Based on qualitative data from 763 academic Science, Technology, Engineering, Mathematics (STEM) women at 202 universities, we examined adaptation to disrupted work-nonwork boundaries and identified workplace contextual features associated with these adaptations. Results show that STEM women varied in their adaptation. Many women adapted their professional image management approaches: From concealing nonwork roles-particularly when in less supportive contexts, to revealing them-often to challenge existing ideal worker norms and advocate for change. Also, women adapted through varying forms of role sacrifice; trading off one role's execution for another, mental detachment through psychological role withdrawal, or abandoning role duties through behavioral role exit. Notably, some sacrificed their nonwork roles, although the dominant media narrative highlights women sacrificing work roles. Work contextual features associated with boundary management adaptation include structural support (e.g., flexibility) and social support (e.g., empathy). Results illuminate the complex decisions faced by STEM women when they lose the scaffolding supporting their work-nonwork interface. Moreover, the results have practical and theoretical implications for advancing workforce gender equity, and for supporting all employees' work-nonwork boundary management. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Given the huge increase in remote work that has accompanied the Coronavirus disease (COVID-19) pandemic, understanding predictors of performance and wellbeing among remote workers has never been more timely. Effective communication is commonly cited as key to remote worker success, yet communication variables are rarely incorporated into remote work research. In the present study, we examined the relationship between communication frequency, communication quality, and supervisor-set communication expectations with daily job performance and burnout in an occupationally-diverse sample of employees. We used an experience sampling design and our hypotheses were tested with data collected over a 4-week period with a sample of 471 employees who shifted to full-time remote work due to COVID-19. Results indicated that daily communication quality was associated with daily performance and burnout. In addition, the extent to which supervisors established expectations about communication practices (e.g., expected response times to email) at the onset of the transition to remote work was positively associated with performance, but not burnout. Task interdependence was also tested as a moderator. Task interdependence moderated the relationship between communication quality and performance, such that the relationship was stronger when task interdependence was higher than when it was lower. Task interdependence also moderated the relationship between supervisor-set expectations and performance such that the relationship was stronger when task interdependence was lower than when it was higher. Expected curvilinear relationships between communication frequency and outcomes were not detected. Based on our findings, we provide recommendations for practice and future research. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

To identify novel bioactive compounds, an image-based, cell culture screening of natural product extracts was conducted. Specifically, our screen was designed to identify phytochemicals that might phenocopy inhibition of the chromosomal passenger protein complex in eliciting mitotic and cytokinetic defects. A known alkaloid, scoulerine, was identified from the rhizomes of the plant Corydalis decumbens as being able to elicit a transient mitotic arrest followed by either apoptosis induction or polyploidy. In examining the mitotic abnormality further, we observed that scoulerine could elicit supernumerary centrosomes during mitosis, but not earlier in the cell cycle. The localization of NUMA1 at spindle poles was also inhibited, suggesting diminished potential for microtubule recruitment and spindle-pole focusing. Polyploid cells emerged subsequent to cytokinetic failure. The concentration required for scoulerine to elicit all its cell division phenotypes was similar, and an examination of related compounds highlighted the requirement for proper positioning of a hydroxyl and a methoxy group about an aromatic ring for activity. Mechanistically, scoulerine inhibited AURKB activity at concentrations that elicited supernumerary centrosomes and polyploidy. AURKA was only inhibited at higher concentrations, so AURKB inhibition is the likely mechanism by which scoulerine elicited division defects. AURKB inhibition was never complete, so scoulerine may be a suboptimal AURK inhibitor or work upstream of the chromosomal passenger protein complex to reduce AURKB activity. Scoulerine inhibited the viability of a variety of human cancer cell lines. Collectively, these findings uncover a previously unknown activity of scoulerine that could facilitate targeting human cancers. Scoulerine, or a next-generation analogue, may be useful as a nontoxic component of combination therapies where inhibiting the chromosomal passenger protein complex is desired.

A synthetic lethal effect arises when a cancer-associated change introduces a unique vulnerability to cancer cells that makes them unusually susceptible to a drug's inhibitory activity. The synthetic lethal approach is attractive because it enables targeting of cancers harboring specific genomic or epigenomic alterations, the products of which may have proven refractory to direct targeting. An example is cancer driven by overexpression of MYC. Here, we conducted a high-content screen for compounds that are synthetic lethal to elevated MYC using a small-molecule library to identify compounds that are closely related to, or are themselves, regulatory-approved drugs. The screen identified dimethylfasudil, a potent and reversible inhibitor of Rho-associated kinases, ROCK1 and ROCK2. Close analogs of dimethylfasudil are used clinically to treat neurologic and cardiovascular disorders. The synthetic lethal interaction was conserved in rodent and human cell lines and could be observed with activation of either MYC or its paralog MYCN. The synthetic lethality seems specific to MYC overexpressing cells as it could not be substituted by a variety of oncogenic manipulations and synthetic lethality was diminished by RNAi-mediated depletion of MYC in human cancer cell lines. Collectively, these data support investigation of the use of dimethylfasudil as a drug that is synthetic lethal for malignancies that specifically overexpress MYC., Competing Interests: J.Z., S.Z., Q.S., T.D.A. and D.Y. are affiliated with the commercial company Anticancer Bioscience, Ltd. (ACB), which is actively engaged in the development of therapeutics, including a program related to research reported here. ACB has filed the following patent: US20180346995A1 Process for Exploiting Synthetic Lethality Based on OverExpression of MYC Oncogene. T.D.A. is also founder in Tradewind Bioscience, Inc., which holds no interest or ownership in the results presented in this manuscript or the patent listed above.

Rationale: Glomerular capillaries are lined with a highly specialized fenestrated endothelium and contribute to the glomerular filtration barrier. The Notch signaling pathway is involved in regulation of glomerular filtration barrier, but its role in glomerular endothelium has not been investigated due to the embryonic lethality of animal models with genetic modification of Notch pathway components in the endothelium., Objective: To determine the effects of aberrant activation of the Notch signaling in glomerular endothelium and the underlying molecular mechanisms., Methods and Results: We established the ZEG-NICD1 (notch1 intracellular domain)/Tie2-tTA/Tet-O-Cre transgenic mouse model to constitutively activate Notch1 signaling in endothelial cells of adult mice. The triple transgenic mice developed severe albuminuria with significantly decreased VE-cadherin (vascular endothelial cadherin) expression in the glomerular endothelium. In vitro studies showed that either NICD1 (Notch1 intracellular domain) lentiviral infection or treatment with Notch ligand DLL4 (delta-like ligand 4) markedly reduced VE-cadherin expression and increased monolayer permeability of human renal glomerular endothelial cells. In addition, Notch1 activation or gene knockdown of VE-cadherin reduced the glomerular endothelial glycocalyx. Further investigation demonstrated that activated Notch1 suppression of VE-cadherin was through the transcription factors SNAI1 (snail family transcriptional repressor 1) and ERG (Ets related gene), which bind to the -373 E-box and the -134/-118 ETS (E26 transformation-specific) element of the VE-cadherin promoter, respectively., Conclusions: Our results reveal novel regulatory mechanisms whereby endothelial Notch1 signaling dictates the level of VE-cadherin through the transcription factors SNAI1 and ERG, leading to dysfunction of glomerular filtration barrier and induction of albuminuria. Graphic Abstract: A graphic abstract is available for this article.

An emerging body of research has investigated the relationship between helping (as a type of organizational citizenship behaviour) and emotional exhaustion (as an aspect of employee health). Research has demonstrated a significant relationship between helping and emotional exhaustion, but the theoretical arguments for the causal direction vary across studies. Specifically, some researchers have conceptualized helping as an outcome of emotional exhaustion, while others have regarded helping as a predictor of emotional exhaustion. This lack of theoretical clarity in directionality hinders the field's ability to summarize existing empirical findings cohesively and elucidate theoretical mechanisms. Therefore, this study attempts to clarify the theoretical directionality between helping and emotional exhaustion using four waves of data collected at 6-month intervals. Autoregressive cross-lagged analyses with auto-correlations revealed that more helping was associated with less future emotional exhaustion from Wave 1 to Wave 2, but from Wave 2 to Wave 3, the directionality reversed, as less emotional exhaustion significantly predicted more future helping, and from Wave 3 to Wave 4, both prediction directions were no longer significant. The findings suggest that helping and emotional exhaustion reciprocally affect each other, though the reciprocal pattern may disappear across time. The present study sheds light on the theoretical relationship between helping and emotional exhaustion, and provides theoretical and practical implications., (© 2020 John Wiley & Sons, Ltd.)

Inhibition of Aurora-B kinase is a synthetic lethal therapy for tumors that overexpress the MYC oncoprotein. It is currently unclear whether co-occurring oncogenic alterations might influence this synthetic lethality by conferring more or less potency in the killing of tumor cells. To identify such modifiers, isogenic cell lines were utilized to test a variety of cancer genes that have been previously demonstrated to promote survival under conditions of cellular stress, contribute to chemoresistance and/or suppress MYC-primed apoptosis. It was found that Bcl-2 and Bcl-xL, two antiapoptotic members of the Bcl-2 family, can partially suppress the synthetic lethality, but not multinucleation, elicited by a pan-aurora kinase inhibitor, VX-680. Suppression was show to stem from the inhibition of autophagy, specifically in multinucleated cells, rather than a general inhibition of apoptosis. The anti-autophagic activity of Bcl-2 also impacted polyploid cell recovery in colony-forming assays, suggesting a route of escape from MYC-VX-680 synthetic lethality that may have clinical consequences. These findings expand on previous conclusions that autophagic death of VX-680-induced polyploid cells is mediated by Atg6. Bcl-2 and Bcl-xL negatively modulate MYC-VX-680 synthetic lethality and it is the anti-autophagic activity of these two Bcl-2 family proteins, specifically in multinucleate cells, that contributes to resistance to Aurora kinase-targeting drugs., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A sizable body of research has established work-family conflict and its nomological network. Despite decades of research, we have yet to form a precise understanding of what happens when a conflict arises. The current research addresses this question using a growth modeling, episodic approach. We use stressor-strain and allostatic load theories to examine changes in daily patterns of psychological (fatigue, negative affect) and physiological (heart rate, blood pressure) strains that occur during and after a work-family conflict episode. We found some evidence for acute changes in psychological strain during and after work-to-family conflict episodes. Daily family-to-work conflict was associated with mixed reactions. State fatigue and heart rate decreased at the time of a family-to-work conflict, although state negative affect increased at the time of family-to-work conflict, and state fatigue increased more rapidly throughout the day after the second time family-to-work conflict was experienced. Additionally, we found evidence that state negative affect increases throughout the day as work-to-family conflict episodes accumulate. Daily family-to-work conflict accumulation was also associated with decreased fatigue, increased state negative affect, and increased systolic blood pressure. Lagged analyses showed some evidence that negative mood predicts work-family conflict occurrence within the next few hours. Implications for the theoretical relationship between work-family conflict and strain are discussed. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Through the lens of boundary theory, we systematically examined cultural context as a moderator of relationships between work-family conflict and its key theoretical predictors (work/family hours and work/family demands) and outcomes (job satisfaction, family satisfaction, and life satisfaction). We used 2 different approaches to examine cultural variation in the strength of work-family conflict relationships: (a) individual cultural values (collectivism, power distance, uncertainty avoidance); and (b) regional cluster configurations (e.g., Eastern Europe, South Asia). Our meta-analytic investigation is based on data drawn from 332 studies (2,733 effect sizes) that represent 58 different countries. Consistent with prediction, results revealed that collectivism moderated WIF/FIW and satisfaction outcomes such that relationships were weaker in more collectivistic contexts than in less collectivistic contexts. Little evidence was found to support power distance or uncertainty avoidance as individual cultural moderators. Findings also indicated that work-family conflict relationships differ in strength as a function of regional clusters, lending support to the use of configural approaches to examine cross-cultural variation. Overall, our findings suggest that domain demands are a robust predictor of work-family conflict across countries and that affective correlates to work-family conflict meaningfully vary in strength as a function of cultural context. (PsycInfo Database Record (c) 2020 APA, all rights reserved).

Background: Previous studies suggested that the metabolism is differently reprogrammed in the major subtypes of non-small cell lung cancer (NSCLC), squamous cell carcinomas (SCC) and adenocarcinomas (AdC). However, a comprehensive analysis of this differential metabolic reprogramming is lacking., Methods: Publicly available gene expression data from human lung cancer samples and cell lines were analysed. Stable isotope resolved metabolomics were performed on SCC and ADC tumours in human patients and in freshly resected tumour slices., Results: Analysis of multiple transcriptomics data from human samples identified a SCC-distinguishing enzyme gene signature. SCC tumours from patients infused with [U- 13 C]-glucose and SCC tissue slices incubated with stable isotope tracers demonstrated differential glucose and glutamine catabolism compared to AdCs or non-cancerous lung, confirming increased activity through pathways defined by the SCC metabolic gene signature. Furthermore, the upregulation of Notch target genes was a distinguishing feature of SCCs, which correlated with the metabolic signature. Notch and MYC-driven murine lung tumours recapitulated the SCC-distinguishing metabolic reprogramming. However, the differences between SCCs and AdCs disappear in established cell lines in 2D culture., Conclusions: Our data emphasise the importance of studying lung cancer metabolism in vivo. They also highlight potential targets for therapeutic intervention in SCC patients including differentially expressed enzymes that catalyse reactions in glycolysis, glutamine catabolism, serine, nucleotide and glutathione biosynthesis.

The current study investigates differential relationships between challenge and hindrance stressors and metabolic risk factors using data from the National Survey of Midlife Development in the United States (MIDUS II). Guided by the challenge-hindrance stressor model and the allostatic load model, we test two theoretically driven paths: a direct physiological path and an indirect path via health behaviors (i.e., high-risk eating, cigarette smoking, and alcohol consumption). Challenge stressors versus hindrance stressors were hypothesized to differentially predict health behaviors and metabolic risk factors. Results favor the health behavior-mediated pathway in comparison with the direct physiological pathway. High-risk food consumption served as a link between hindrance stressors and metabolic risk factors. Some evidence supported smoking as a link between hindrance stressors and metabolic risk factors, and alcohol consumption as a link between challenge stressors and metabolic risk factors. The pattern of findings supported the challenge-hindrance distinction, particularly in relation to health behaviors. By combining the challenge-hindrance and allostatic load literatures, our study theoretically and empirically extends knowledge of how work stressors relate to physiological outcomes. Moreover, we also extend the nomological network of challenge and hindrance stressors to behavioral and physiological outcomes. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Netrin4 (NTN4) is a chemotropic factor that regulates angiogenesis. We found that endothelial expression of the activated, intracellular domain of Notch1 (NICD1), significantly up-regulated NTN4 mRNA as well as intracellular NTN4 protein in both transgenic mice and cultured human umbilical vein endothelial cells (HUVECs). Notch1 activation also increased NTN4 secretion from HUVECs. We subsequently demonstrated that NICD1 bound to CSL (CBF1, Suppressor of Hairless, Lag-1), a core component of Notch transcription complex, at the -53 element of the human NTN4 gene promoter. Loss of the -53 element compromised NICD1-induced NTN4 expression. Our results suggest a conserved role for Notch signalling in transcriptional regulation of endothelial NTN4., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Rationale: Research using the challenge-hindrance stressor framework shows hindrance stressors tend to have detrimental affective and work-related outcomes, whereas challenge stressors have relatively more salutary affective and work-related outcomes. The extent to which this pattern extends to health behaviors, such as sleep, is unknown., Objective: The current study examines challenge and hindrance work stressors in relation to sleep quantity and quality., Methods: We use survey data from the MIDUS II (Phase 1 and Phase 4) to test the relationship between self-reported challenge and hindrance stressors and assessments of sleep, including cross-sectional and prospective indicators of sleep quantity, sleep quality (sleep onset latency, sleep disturbance), and sleepiness., Results: Hindrance stressors are associated with prospective sleep quantity, as well as cross-sectional and prospective sleep quality and sleepiness. Further, the pattern of results for sleep quality and sleepiness reflects the expected challenge-hindrance pattern, such that hindrance stressors are more strongly associated with poor sleep quality and sleepiness than are challenge stressors. The same challenge-hindrance pattern was not significant sleep quantity. Work hours and time lag generally did not moderate associations between work stressors and sleep., Conclusion: The challenge-hindrance pattern holds for sleep quality and sleepiness, but not sleep quantity. Relationships appear to be consistent across time and differences in work hours. Results have implications for expanding the challenge-hindrance stressor framework and underline the importance of distinguishing between different types of stressors and sleep dimensions., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The job demands-resources model is a dominant theoretical framework that describes the influence of job demands and job resources on employee strain. Recent research has highlighted that the effects of job demands on strain vary across cultures, but similar work has not explored whether this is true for job resources. Given that societal characteristics can influence individuals' cognitive structures and, to a lesser extent, values in a culture, we address this gap in the literature and argue that individuals' strain in reaction to job resources may differ across cultures. Specifically, we theorize that the societal cultural dimensions of individualism-collectivism and uncertainty avoidance shape individual-level job resource-strain relationships, as they dictate which types of resources (i.e., individual vs. group preference-oriented and uncertainty-reducing vs. not) are more likely to be valued, used, or effective in combating strain within a culture. Results revealed that societal individualism-collectivism and uncertainty avoidance independently moderated the relationships between certain job resources (i.e., job control, participation in decision making, and clear goals and performance feedback) and strain (i.e., job satisfaction and turnover intentions). This study expands our understanding of the cross-cultural specificity versus generalizability of the job demands-resources model.

Sepsis, the systemic inflammatory responses after infection, remains a serious cause of morbidity and mortality in critically ill patients. The anti-malarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we examined the effects of DHA on sepsis-induced acute kidney injury (AKI) and explored the mechanism underlying its mode of action in AKI. In a lipopolysaccharide (LPS)-induced mouse model, we observed that DHA treatment ameliorated glomerular injury, and relieved elevation of the urine albumin to creatinine ratio (UACR) and serum creatinine. At a concentration of 25 μM, DHA had no effect on overall cellular viability or apoptosis in assays with human renal glomerular endothelial cells (HRGECs), but significantly inhibited the tumor necrosis factor-α (TNF-α)-induced hyperpermeability of HRGEC monolayers. We found that TNF-α decreases the expression of the junctional protein occludin in HRGECs, which is reversed by DHA. Taken together, our results demonstrate that DHA decreases permeability of the glomerular endothelium by maintenance of occludin expression. This suggests DHA may have therapeutic utility in sepsis-induced AKI., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

The relationship between social support and work-family conflict is well-established, but the notion that different forms, sources, and types of social support as well as contextual factors can alter this relationship has been relatively neglected. To address this limitation, the current study provides the most comprehensive and in-depth examination of the relationship between social support and work-family conflict to date. We conduct a meta-analysis based on 1021 effect sizes and 46 countries to dissect the social support and work-family conflict relationship. Using social support theory as a theoretical framework, we challenge the assumption that social support measures are interchangeable by comparing work/family support relationships with work-family conflict across different support forms (behavior, perceptions), sources (e.g., supervisor, coworker, spouse), types (instrumental, emotional), and national contexts (cultural values, economic factors). National context hypotheses use a strong inferences paradigm in which utility and value congruence theoretical perspectives are pitted against one another. Significant results concerning support source are in line with social support theory, indicating that broad sources of support are more strongly related to work-family conflict than are specific sources of support. In line with utility perspective from social support theory, culture and economic national context significantly moderate some of the relationships between work/family support and work interference with family, indicating that social support is most beneficial in contexts in which it is needed or perceived as useful. The results suggest that organizational support may be the most important source of support overall. (PsycINFO Database Record, ((c) 2018 APA, all rights reserved).)

The antimalarial agent dihydroartemisinin (DHA) has been shown to be anti-inflammatory. In this study, we found that DHA increased the expression of the junctional protein vascular endothelial (VE)-cadherin in human renal glomerular endothelial cells. In addition, DHA inhibited TGF-β RI-Smad2/3 signalling and its downstream effectors SNAIL and SLUG, which repress VE-cadherin gene transcription. Correspondingly, DHA decreased the binding of SNAIL and SLUG to the VE-cadherin promoter. Together, our results suggest an effect of DHA in regulating glomerular permeability by elevation of VE-cadherin expression., (© 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

There is growing interest among organizational researchers in tapping into alternative sources of data beyond self-reports to provide a new avenue for measuring behavioral constructs. Use of alternative data sources such as wearable sensors is necessary for developing theory and enhancing organizational practice. Although wearable sensors are now commercially available, the veracity of the data they capture is largely unknown and mostly based on manufacturers' claims. The goal of this research is to test the validity and reliability of data captured by one such wearable badge (by Humanyze) in the context of structured meetings where all individuals wear a badge for the duration of the encounter. We developed a series of studies, each targeting a specific sensor of this badge that is relevant for structured meetings, and we make specific recommendations for badge data usage based on our validation results. We have incorporated the insights from our studies on a website that researchers can use to conduct validation tests for their badges, upload their data, and assess the validity of the data. We discuss this website in the corresponding studies.

Lung adenocarcinoma (LAC) is the leading cause of cancer-related death worldwide. Aberrant expression of genes expressed preferentially in the lung tumor vasculature may yield clues for prognosis and treatment. Von Willebrand factor (vWF) is a large multifunctional glycoprotein with a well-known function in hemostasis. However, vWF has been reported to exert an anti-tumor effect, independent of its role in hemostasis. We investigated the expression of vWF in LAC through immunohistochemical staining of tumor tissue microarrays (TMAs). We found that vWF was overexpressed preferentially in the tumor vasculature of LAC compared with the adjacent tissue vasculature. Consistently, elevated vWF expression was found in endothelial cells (ECs) of fresh human LAC tissues and transplanted mouse LAC tissues. To understand the mechanism underlying vWF up-regulation in LAC vessels, we established a co-culture system. In this system, conditioned media (CM) collected from A549 cells increased vWF expression in human umbilical vein endothelial cells (HUVECs), suggesting enhanced expression is regulated by the LAC secretome. Subsequent studies revealed that the transcription factor GATA3, but not ERG, a known regulator of vWF transcription in vascular cells, mediated the vWF elevation. Chromatin immunoprecipitation (ChIP) assays validated that GATA3 binds directly to the +220 GATA binding motif on the human vWF promoter and A549 conditioned media significantly increases the binding of GATA3. Taken together, we demonstrate that vWF expression in ECs of LAC is elevated by the cancer cell-derived secretome through enhanced GATA3-mediated transcription., Competing Interests: CONFLICTS OF INTEREST The authors declare no conflicts of interest.

As part of the 20th anniversary celebration for the Journal of Occupational Health Psychology (JOHP), this article reviews the literature on work-family with a special emphasis on research published in JOHP and that with health-related implications. We provide a retrospective overview of work-family research, tracing key papers and major theoretical constructs and themes. We examine the research needs identified by Westman and Piotrkowski (1999) and offer an assessment of the extent that work-family research has addressed those needs. Then we move on to discuss contemporary issues in the field today that constitute directions for future research. Specifically we discuss intervention studies, multilevel approaches, temporality and dynamic change, managerial perspectives, and diverse work settings. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

As part of the centennial celebration for the Journal of Applied Psychology , this article reviews the literature on organizational socialization and mentoring. Our review includes a comparison of organizational socialization and mentoring as processes for employee adjustment and development, the historical context that fueled the emergence of these two areas of study, and a chronological mapping of key foundations, trends, themes that emerged across time, and major milestones. Along the way, a special emphasis is placed on research published in the Journal of Applied Psychology and high impact work is highlighted. We conclude with a discussion of five areas for future research. Specifically, we outline ideas for bridging the socialization and mentoring literatures, better understanding and capturing dynamic processes across time, the development of multilevel theories and models, addressing causality, and considering the implications for organizational socialization and mentoring research based on how technology is changing the way we work. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

The von Willebrand factor (vWF) is a plasma glycoprotein that plays an essential role in hemostasis by supporting platelet adhesion and thrombus formation in response to vascular injury. Plasma levels of vWF are an independent risk factor for patients with acute myocardial infarction (AMI); however, clinical data have demonstrated a marked variation of vWF levels in patients with AMI, the reason for which has not yet been identified. In the present study, a rat model of ST-segment elevation AMI was established, and cardiac and peripheral blood was collected for a time-course examination of the plasma levels of vWF and tumor necrosis factor-α (TNF-α). The level of vWF in the blood plasma increased, peaked at 1 h and decreased to normal levels by day 7 following AMI, while the level of TNF-α peaked at 24 h and remained elevated until day 7. The effects of TNF-α on vWF secretion and expression were examined in cultured human umbilical vascular endothelial cells (HUVECs). TNF-α treatment increased vWF secretion from the HUVECs but inhibited the mRNA and protein expression of vWF in the HUVECs. These results indicate that vWF secretion from endothelial cells is transiently elevated following AMI, and then decreases as the expression of vWF is inhibited by TNF-α. The present study increases the understanding of the pathophysiology of vWF and indicates that the determination of vWF levels may be useful in the clinical evaluation of AMI.

Telecommuting has become an increasingly popular work mode that has generated significant interest from scholars and practitioners alike. With recent advances in technology that enable mobile connections at ever-affordable rates, working away from the office as a telecommuter has become increasingly available to many workers around the world. Since the term telecommuting was first coined in the 1970s, scholars and practitioners have debated the merits of working away from the office, as it represents a fundamental shift in how organizations have historically done business. Complicating efforts to truly understand the implications of telecommuting have been the widely varying definitions and conceptualizations of telecommuting and the diverse fields in which research has taken place.Our objective in this article is to review existing research on telecommuting in an effort to better understand what we as a scientific community know about telecommuting and its implications. In so doing, we aim to bring to the surface some of the intricacies associated with telecommuting research so that we may shed insights into the debate regarding telecommuting's benefits and drawbacks. We attempt to sift through the divergent and at times conflicting literature to develop an overall sense of the status of our scientific findings, in an effort to identify not only what we know and what we think we know about telecommuting, but also what we must yet learn to fully understand this increasingly important work mode.After a brief review of the history of telecommuting and its prevalence, we begin by discussing the definitional challenges inherent within existing literature and offer a comprehensive definition of telecommuting rooted in existing research. Our review starts by highlighting the need to interpret existing findings with an understanding of how the extent of telecommuting practiced by participants in a study is likely to alter conclusions that may be drawn. We then review telecommuting's implications for employees' work-family issues, attitudes, and work outcomes, including job satisfaction, organizational commitment and identification, stress, performance, wages, withdrawal behaviors, and firm-level metrics. Our article continues by discussing research findings concerning salient contextual issues that might influence or alter the impact of telecommuting, including the nature of the work performed while telecommuting, interpersonal processes such as knowledge sharing and innovation, and additional considerations that include motives for telecommuting such as family responsibilities. We also cover organizational culture and support that may shape the telecommuting experience, after which we discuss the community and societal effects of telecommuting, including its effects on traffic and emissions, business continuity, and work opportunities, as well as the potential impact on societal ties. Selected examples of telecommuting legislation and policies are also provided in an effort to inform readers regarding the status of the national debate and its legislative implications. Our synthesis concludes by offering recommendations for telecommuting research and practice that aim to improve the quality of data on telecommuting as well as identify areas of research in need of development., (© The Author(s) 2015.)

Trichostatin A (TSA) is a histone deacetylase inhibitor and a potential therapeutic for various malignancies. The in vivo effect of TSA, however, has not been investigated in a transgenic lung cancer model. Previously, we generated transgenic mice with overexpression of Groucho-related-gene 1 (Grg1) and these mice all developed mucinous lung adenocarcinoma. Grg1 is a transcriptional co-repressor protein, the function of which is thought to depend on HDAC activity. However, functions outside the nucleus have also been proposed. We tested the supposition that Grg1-induced tumorigenesis is HDAC-dependent by assaying the therapeutic effect of TSA in the Grg1 transgenic mouse model. We found that TSA significantly inhibited lung tumorigenesis in Grg1 transgenic mice (p < 0.01). TSA did not affect overall Grg1 protein levels, but instead reduced ErbB1 and ErbB2 expression, which are upregulated by Grg1 in the absence of TSA. We confirmed this effect in A549 cells. Furthermore, lapatinib, an inhibitor of both ErbB1 and ErbB2, effectively masked the effect of TSA on the inhibition of A549 cell proliferation and migration, suggesting TSA does work, at least in part, by downregulating ErbB receptors. We additionally found that TSA reduced the expression of VEGF and VEGFR2, but not basic FGF and FGFR1. Our findings indicate that TSA effectively inhibits Grg1-induced lung tumorigenesis through the down-regulation of ErbB1 and ErbB2, as well as reduced VEGF signaling. This suggests TSA and other HDAC inhibitors could have therapeutic value in the treatment of lung cancers with Grg1 overexpression., (Copyright © 2015 Elsevier Inc. All rights reserved.)