Ethics

The Effect of Top Management Trustworthiness on Turnover Intentions via Negative Emotions: The Moderating Role of Gender Abstract Based on a field study (N = 303), this paper explores the differential role that perceived top management trustworthiness has on female and male employees' negative emotions and turnover intentions in organizations. A theoretical model is established that explicates a negative indirect effect of perceived top management trustworthiness on employee turnover intentions through employee negative emotions. The results reveal that there is a negative relationship between perceived top management trustworthiness and employee negative emotions and resulting turnover intentions and that this effect is stronger for female employees than for male employees. These results demonstrate the pivotal role played by top management trustworthiness, provide an explanation for the turnover gender gap, and highlight the subjectivity in reactions to trustworthiness perceptions. The implications for organizations are discussed in line with the need for top management to positively influence employees and particularly women, to retain them in their workforce.

When and for Whom Ethical Leadership is More Effective in Eliciting Work Meaningfulness and Positive Attitudes: The Moderating Roles of Core Self-Evaluation and Perceived Organizational Support Abstract Despite urgent calls for more research on the integration of business ethics and the meaning of work, to date, there have been few corresponding efforts, and we know surprisingly little about this relationship. In this study, we address this issue by examining when and for whom ethical leadership is more (or less) effective in promoting a sense of work meaningfulness among employees, and their subsequent work attitudes. Drawing on the contingency theories of leadership and work meaningfulness literature, we speculate that both employees' core self-evaluation (CSE; as a dispositional characteristic) and perceived organizational support (POS; as a situational characteristic) moderate the relationship, but in different ways, and these associations carry over to employees' subsequent work attitudes in terms of job satisfaction, organizational commitment and turnover intention. We test our hypotheses with two-wave survey data collected from 377 employees. Results indicate that ethical leadership is effective in eliciting work meaningfulness and attitudes for employees higher in CSE or when POS is lower, and ineffective for those lower in CSE or when POS is higher. A supplementary analysis reveals a three-way interaction between ethical leadership, CSE and POS in predicting a sense of work meaningfulness and subsequent work attitudes. Our research cautions that ethical leadership is not a universally positive practice; it can be ineffective or even have a negative impact under some circumstances.

The Moral Entrepreneur: A New Component of Ethical Leadership Abstract Ethical leadership has become a popular subject of empirical research in recent years. Most studies follow Brown et al.'s (Organ Behav Hum Decis Process, 97:117–134, 2005) definition of ethical leadership, which consists of two components: the moral person and the moral manager. In this paper, I argue for a third relevant component: i.e., the moral entrepreneur who creates a new ethical norm. Viewing moral entrepreneurship as a new component of ethical leadership opens up avenues for studying various antecedents and outcomes of ethical leadership that have not been acknowledged so far, or at least, not adequately.

The Interpersonal Benefits of Leader Mindfulness: A Serial Mediation Model Linking Leader Mindfulness, Leader Procedural Justice Enactment, and Employee Exhaustion and Performance Abstract Although it is an increasingly popular assumption that leader mindfulness may positively affect leader behaviors and, in turn, employee outcomes, to date, little empirical evidence supports this view. Against this backdrop, the present research seeks to develop and test a serial mediation model of leader mindfulness. Specifically, we propose that leader mindfulness enhances employee performance and that this relationship is explained by increased leader procedural justice enactment and, subsequently, reduced employees' emotional exhaustion. We conducted three studies to test this model. Study 1 involved employees from a wide range of organizations in the USA (N = 275 employees). Study 2 used a sample of leaders and employees from China and measured our model variables at three different points in time (N = 182 employees and 54 leaders). Both studies provide consistent support for our hypotheses. Finally, Study 3 involved a laboratory experiment in which 62 senior executives were assigned to either a mindfulness induction or to a control condition. Again, results revealed a significant and positive link between leader mindfulness and leader procedural justice enactment. In sum, these findings expand our understanding of mindfulness to the domain of leadership, a key area of organizational research. Moreover, they complement prior studies by showing that mindfulness dynamics go beyond intrapersonal effects but also influence the attitudes and behaviors of others. We discuss our findings in light of their contributions to the mindfulness, ethics, and leadership literatures and point out implications for practice.

An Identity Perspective on Ethical Leadership to Explain Organizational Citizenship Behavior: The Interplay of Follower Moral Identity and Leader Group Prototypicality Abstract Despite the proliferation of research on ethical leadership, there remains a limited understanding of how specifically the assumingly moral component of this leadership style affects employee behavior. Taking an identity perspective, we integrate the ethical leadership literature with research on the dynamics of the moral self-concept to posit that ethical leadership will foster a sense of moral identity among employees, which then inspires followers to adopt more ethical actions, such as increased organization citizenship behavior (OCB). We further argue that these identity effects should be more pronounced when leaders are perceived to be group prototypical, as their actions then speak louder to followers' sense of identity. Two studies—a scenario experiment with 138 participants and a field study with 225 employees—provided support for our hypothesized moderated mediation model. Perceived ethical leadership positively affected OCB via followers' moral identity but only under conditions of high perceived leader group prototypicality. We discuss how the identity pathway of ethical leadership can facilitate novel theorizing about moral transference. Our findings also suggest that, when hiring external ethical leaders or training internal managers, practitioners are well advised to consider that these individuals may only be effective in morally transforming followers when they are perceived as prototypical for the group.

Corporate Citizenship and Employee Outcomes: Does a High-Commitment Work System Matter? Abstract Interest in corporate citizenship (CC) has been burgeoning in the academic and managerial realms for decades. While a psychological CC climate has been conceptualized and has received empirical support for its relationship with employee outcomes, the organizational climate perspective of CC has not yet been explored. In the present study, we develop and examine a mediated moderation model that elaborates the underlying psychological process and the contingency of organizational CC climate and its individual outcomes. We follow 539 employees in 26 firms for approximately one year in Taiwan. We find that organizational CC climate is positively related to employees' organizational identification (OI) and that the firm's high-commitment work system (HCWS) can augment the effect of CC on employees' OI. In addition, employees' OI plays a psychological process role in mediating the interactive effect of the firm's CC and HCWS on employees' workplace outcomes, including their job satisfaction (JS) and turnover intention. The findings shed light on the alignment of CC and human resource functions and argue that the Confucian Asian context may act as a stepping stone for the impact of CC on employees' attitudes. The study offers valuable implications for both researchers and practitioners.

"Daring to Care": Challenging Corporate Environmentalism Abstract Corporate engagements with pressing environmental challenges focus on expanding the role of the market, seeking opportunities for growth and developing technologies to manage better environmental resources. Such approaches have proved ineffective. I suggest that a lack of meaningful response to ecological degradation and climate change is inevitable within a capitalist system underpinned by a logics of appropriation and an instrumental rationality that views the planet as a means to achieve economic ends. For ecofeminism, these logics are promulgated through sets of hierarchical and interrelated dualisms which define the human in opposition to the realm of "nature". This has led to the resilience of ecosystems, social reciprocity and care being unvalued or undervalued. An ecofeminist, care-sensitive ethics is proposed that focuses on the interconnections between human and nonhuman nature and on affective engagements with the living world. A practical morality is developed that sees the self not as atomized nor as self-optimizing, but as a self in relationship. Such an ethics is necessary to motivate action to contest capitalism's binary thinking, evident within corporate environmentalism, which has re-made the web of life in ways that are not conducive to planetary flourishing.

'Lower than a Snake's Belly': Discursive Constructions of Dignity and Heroism in Low-Status Garbage Work Abstract In this paper, we consider how dignity is discursively constructed in the context of work dominated by physicality and dirt. Based on semi-structured interviews with garbage workers, our analysis considers how the deprivations they experience are cast through discourses intended to construct their individual and collective worth. We consider the manner in which dignity maybe denied to such workers through popular repudiations of individuality and status. We demonstrate how this positioning arises from contact with physical dirt, and associations with socially dirty work based on ascriptions of servility, abuse and ambivalence. We go on to consider how garbage workers respond to this positioning through discourses of 'everyday heroism'. Heroism is evoked through three inter-related narratives that speaks to a particular type of masculinity. The first takes the form of a classic process of reframing and recalibration through which workers not only renegotiate their public position and status, but also point to the inherent value to be had in working with dirt as part of that which we identify as a process of 'affirmation'. The second narrative arises from the imposition of favourable social and occupational comparisons that effectively elevate garbage collectors' social position. The third discourse—and previously unobserved in respect of garbage work—centres on paternalistic practices of care. Combined, these discourses disrupt the generally held view that dirty work is antithetical to heroism and wounds dignity.

Uncivil Supervisors and Perceived Work Ability: The Joint Moderating Roles of Job Involvement and Grit Abstract Uncivil behavior by leaders may be viewed as an effective way to motivate employees. However, supervisor incivility, as a form of unethical supervision, may be undercutting employees' ability to do their jobs. We investigate linkages between workplace incivility and perceived work ability (PWA), a variable that captures employees' appraisals of their ability to continue working in their jobs. We draw upon the appraisal theory of stress and social identity theory to examine incivility from supervisors as an antecedent to PWA, and to investigate job involvement and grit as joint moderators of this association. Results from data collected in two samples of working adults provided evidence for three-way interactions in relation to PWA. Among employees with high levels of grit, there was no significant relation between supervisor incivility and PWA, regardless of employee job involvement. However, we found some evidence that for those low in grit, having high job involvement was associated with a stronger relationship between supervisor incivility and PWA. Findings attest to the importance of unethical supervisor behavior, showing the potential for supervisor incivility to erode PWA, as well as the importance of grit as a potential buffer.

Exploring the Relationship Between Exclusive Talent Management, Perceived Organizational Justice and Employee Engagement: Bridging the Literature Abstract This conceptual paper explores the relationship between an organization's exclusive talent management (TM) practices, employees' perceptions of the fairness of exclusive TM practices, and the corresponding impact on employee engagement. We propose that in organizations pursuing exclusive TM programs, employee perceptions of organizational justice of the exclusive TM practices may affect their employee engagement, which may influence both organizational and employee outcomes. Building on extant research, we present a conceptual framework depicting the relationship between exclusive TM practices, organizational justice and employee engagement, with social exchange theory and equity theory as the framework's foundation. The propositions in the framework are each supported by the respective literature. The perceived organizational justice and potential ramifications of exclusive TM practices for employees who are not included in corporate talent pools is an under-researched topic. The paper considers the perspectives of employees not included in corporate talent pools and explores how exclusive TM practices, as inputs, could lead to negative employee engagement outputs. In unpacking how exclusive TM practices could impact on employee engagement, the implications for organizations are underlined. The ethics and perceived fairness of exclusive TM practices, which have the potential to marginalize employees and lead to their disengagement, are considered.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Religion and Health

Editor's Introduction for Special Section: Mental Health, The Mind and Consciousness—Tibetan and Western Approaches

Introduction to Special Section of Journal of Religion and Health, 'Mental Health, The Mind and Consciousness: Tibetan and Western Approaches'

Evaluation of Distress and Religious Coping Among Cancer Patients in Turkey Abstract The purpose of this study was to determine distress levels and religious coping styles of cancer patients and the relationship between religious coping styles and distress. This study was conducted as descriptive design. It was determined that 60.7% of the patients experienced distress related to the disease. The field of problem from which the patients mostly experienced distress was physical problems. It was observed that positive coping scores of the patients were higher. There was a negative correlation between their mean scores for positive religious styles and distress total scores.

'I Do Not Exist': Pathologies of Self Among Western Buddhists Abstract This paper presents a clinical case involving a patient suffering 'depersonalisation' who had a psychotic episode at a Buddhist retreat. Recent writing on possible psychological risks of meditation has discussed problems of depersonalisation associated with misunderstandings of the Buddhist conception of non-self (anātman) and emptiness (śūnyatā). Drawing on the work of Winnicott and Bion, this article helps us to realise some of what is at stake in the failure to achieve and maintain an effective sense of self. What does Buddhist talk of non-self really mean? What conditions enable a creatively engaged and meaningful relational life, a sense of aliveness, human flourishing and a capacity for alterity?

Influence of Palliative Care Training on Last-Year Nursing Department Students' Perception on Regarding Spirituality and Spiritual Care: A Single-Group Pretest–Posttest Intervention Study Abstract Spiritual care is a part of integrated care and should not be considered as a separate aspect of palliative care. Spirituality is seen as a requirement that must be met for all patients. The aim of this study is to determine the influence of palliative care on the perception levels of student nurses regarding spirituality and spiritual care. The research was carried out as a single-group pretest–posttest intervention study. The study was conducted with 70 student nurses. Data were collected via personal information form and spirituality and spiritual care grading scale (SSCGS). Frequency, percentage, average, standard deviation, paired sample t-test and Wilcoxon test were used to analyze the data. 55.7% of the students who participated in research stated that they had never heard of spiritual care, and 81.4% of the students stated that they had not obtained any information regarding spiritual care. The point average of the student nurses related to SSCGS was found to be 3.27 ± 0.21 before training and 3.35 ± 0.22 after training. The difference between the total point averages of the student nurses pre- and posttraining was found to be statistically significant (p < 0.05).As a result of the research, the perception of the student nurses regarding spirituality and spiritual support was found to be above the middle and increased significantly after the training. In accordance with these results, it is suggested that spiritual care training should be included more into nursing education.

Beliefs About Etiology and Treatment of Mental Illness Among Korean Presbyterian Pastors Abstract This descriptive study explored pastors' beliefs about etiology and treatment of mental illness. Surveys were completed by mail by 202 Korean and Euro-American Presbyterian clergy. Nearly one-third of Korean pastors viewed bad parenting and demon possession as very important causes of mental illness, in contrast to the more than two-thirds of Euro-American pastors who viewed genetics and chemical imbalances as the most important causes. Compared with their Euro-American counterparts, Korean pastors soundly endorsed spiritual treatment of mental illness. The findings of this study suggest the value of understanding the views of pastors working with populations that underutilize formal mental health services.

Spirituality Experiences in Hemophilia Patients: A Phenomenological Study Abstract Spirituality plays an important role in coping with chronic diseases. However, the meaning of spirituality is not known in hemophilia, as a chronic disease. This study aimed to explore the essence of spirituality in hemophilia patients. This qualitative study with a hermeneutic phenomenological approach was conducted on twelve Muslim adult hemophilia patients. The participants were selected using purposeful sampling. The data were gathered through interview. Then, the data were analyzed using thematic analysis and van Manen's methodological framework. MAX.QDA qualitative software package 2010 was used to import the transcripts and analyze the data. Four themes were identified: "relationship with God," "God as the fulcrum," "strong religious beliefs," and "spiritual satisfaction." "Relationship with God" meant "to ask God for help" and "praying for oneself and others." "God as the fulcrum" consisted of two subthemes, i.e., "hope in God" and "Trust in God." "Strong religious beliefs" also included "belief in openness of God's mercy," "belief in God and the omnipotence of God," and "belief in creation by God." Finally, "spiritual satisfaction" consisted of two subthemes, namely "accepting the providence" and "thanking the divine blessings." Spirituality in hemophilia patients meant having relationship with God who was considered as the fulcrum, strong religious beliefs, and spiritual satisfaction. By understanding the hemophilia patients' spirituality experiences, the nurses and healthcare workers could provide holistic care focused on spirituality. Yet, more studies are recommended to be conducted on hemophilia patients to explore spirituality in other religions.

Intrinsic Religiosity and Health Risk Behaviours Among Black University Students in Limpopo, South Africa Abstract Not much is known about religiosity's protective role against health risk behaviour in the South African context. As such, the study investigated the relationship between intrinsic religiosity and health risk behaviours in a sample of Black university students (N = 335). Two-way ANOVA showed that there were intrinsic religiosity main effects for alcohol use and sexual behaviour, gender and intrinsic religiosity main effects on tobacco and marijuana use, and gender main effects and gender and intrinsic religiosity interaction effects for engagement in physical activity. Thus, religiosity is an inner resource available to avert engagement in varied health risk behaviours.

Marital Adjustment and Its Relationship with Religious Orientations Among Iranian Infertile and Fertile Women: A Cross-Sectional Study Abstract This study aimed to determine the status of marital adjustment and its relationship with religious orientations in fertile and infertile women. This study was conducted on 160 infertile and 320 fertile Muslim Iranian women. There was significant difference in terms of marital adjustment in two groups. There was significant relationship between marital adjustments with intrinsic religious orientation in two groups; however, there was no significant relationship between marital adjustments with extrinsic religious orientation. The results suggest that intrinsic religious orientation is likely to increase marital adjustment in fertile and infertile women. However, further studies should be performed to assess the association of religious orientations with marital adjustment in other communities and religions.

Methodology in Research on the Rainbow Body: Anthropological and Psychological Reflections on Death and Dying Abstract The rainbow body research project, engaging claims of spiritual attainment and personal transformation, enables us to examine key features of anthropological research. Engagement with communities of discourse exposed aspects of the artificial emic–etic divide, allowing the anthropological study of religion to advance methods in religious studies. The study of paranormal phenomena cannot be isolated from societal contextualization. In this instance, a study of death and dying, contextualized in a traditional community, required unique features of engagement for the researcher who would be present to the social dynamics surrounding the death of a person of high repute.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Microbiology

Strategical isolation of efficient chicken feather–degrading bacterial strains from tea plantation soil sample Abstract Chicken feather waste is generally insufficiently utilized despite its high content of protein, constituting an environmental issue. Biodegradation of the waste with enabling microbes provides an advantageous option among the available solutions. In this study, an efficient whole feather–degrading strain was strategically isolated from a soil sample taken from a local tea plantation that has little or nothing to do with feathers. The strain was identified as Bacillus thuringiensis (designated as FDB-10) according to the cloned complete 16S rRNA sequence. The FDB-10 could efficiently degrade briefly heat-treated whole feather (102 °C, 5 min; up to 90% of a maximum concentration of 30 g/L) in a salt medium supplemented with 0.1 g/L yeast extract within 24 h (37 °C, 150 rpm). Addition of carbon sources (glycerol, glucose, starch, Tween 20, Tween 80, 1.25 g/L as glycerol) to the fermentation medium could improve the degradation. However, significant inhibition could be observed when the added carbon source reached the amount usually adopted in the investigation of carbon source preference (1%). Nitrogen source (NH4Cl, (NH4)2SO4, peptone) adversely influenced the performance of the strain. When the molar concentrations of NH4+ were equal for the two salt, the inhibitory effect on degradation of whole feathers was similar. Entirely different from other reported feather-degrading strains showing a preference to melanin-free feather substrates, the strain isolated in this study could degrade melanin-containing feather equally efficiently, and higher protease activity could be detected in the digest mix. As a plus, the strain could degrade feathers in rice wash produced in daily cooking, indicating its potential use in the simultaneous treatment of rice cooker wastewater produced by a rice processing plant. All these results imply that the FDB-10 is a strain with great potential in the biodegradation of feather waste.

Effect of potential probiotic Leuconostoc mesenteroides FB111 in prevention of cholesterol absorption by modulating NPC1L1/PPARα/SREBP-2 pathways in epithelial Caco-2 cells Abstract Mustard kimchi consumption reduces cholesterol levels in rats. To identify lactic acid bacteria (LAB) in kimchi which exert this effect, 20 LAB isolates were evaluated for cholesterol reduction in an in vitro screen. The FB111 strain showed the highest cholesterol-lowering activity and was identified as Leuconostoc mesenteroides. This strain was characterized as a potential probiotic through sequential analyses for resistance to gastrointestinal digestion and bile salts, and adhesion to Caco-2 cells. The Caco-2 cells treated with L. mesenteroides FB111 (6–8 log CFU/mL) showed toxicological effect. The reduction of cholesterol uptake in these cells was inhibited by 48.6% compared to the control and significantly higher than that of the Lactobacillus rhamnosus GG (LGG) strain-treated group after 2-h incubation. The levels of NPC1L1, ABCG5, ABCG8, SREBP-1, SREBP-2, and PPARα gene expression were determined by reverse transcription-quantitative polymerase chain reaction analysis. The L. mesenteroides FB111 and LGG inhibited the mRNA expression of NPC1L1 (P < 0.05), whereas the expression of PPARα was increased. Moreover, the FB111 strain also inhibited the expression of SREBP-2 mRNA. Overall, we found that L. mesenteroides FB111 has efficient cholesterol-lowering effects and might be useful as a probiotic in the food industry.

Targeted 16S rRNA amplicon analysis reveals the diversity of bacterial communities in carwash effluents Abstract This study aimed to analyze the bacterial diversity in carwash effluents and to determine their potential for use in microbial degradation of environmental contaminants. Nine carwash effluent samples were collected for physicochemical and bacterial community diversity analysis using multi-digital probes and 16S rRNA gene amplicon sequencing respectively. The pH of all effluent samples was neutral to slightly alkaline. Oil and grease concentrations ranged from 15.3 to 49.7 mg/L. 16S gene amplicon sequencing of the nine samples produced 45,934-sequence reads, which translated to 13 bacterial phyla, 26 classes, and 43 genera. The most dominant phyla were Proteobacteria, Bacteroidetes, Firmicutes, and Fusobacteria. Canonical correspondence analysis (CCA) showed that the distribution of the phyla Proteobacteria, Bacteroidetes, Acidobacteria, and Verrucomicrobia was influenced by the presence of oil and grease, total petroleum hydrocarbons-gasoline range organics (GRO-TPH), and metals species (Pb, Cu, and Zn). The dominant bacterial genera found in the present study were previously proven to biodegrade hydrocarbons, and their presence in carwash effluents could bode well for in situ natural bioremediation of these contaminated sites.

Role of the antioxidant defense system during the production of lignocellulolytic enzymes by fungi Abstract Fungi are used for the production of several compounds and the efficiency of biotechnological processes is directly related to the metabolic activity of these microorganisms. The reactions catalyzed by lignocellulolytic enzymes are oxidative and generate reactive oxygen species (ROS). Excess of ROS can cause serious damages to cells, including cell death. Thus, the objective of this work was to evaluate the lignocellulolytic enzymes produced by Pleurotus sajor-caju CCB020, Phanerochaete chrysosporium ATCC 28326, Trichoderma reesei RUT-C30, and Aspergillus niger IZ-9 grown in sugarcane bagasse and two yeast extract (YE) concentrations and characterize the antioxidant defense system of fungal cells by the activities of superoxide dismutase (SOD) and catalase (CAT). Pleurotus sajor-caju exhibited the highest activities of laccase and peroxidase in sugarcane bagasse with 2.6 g of YE and an increased activity of manganese peroxidase in sugarcane bagasse with 1.3 g of YE was observed. However, P. chrysosporium showed the highest activities of exoglucanase and endoglucanase in sugarcane bagasse with 1.3 g of YE. Lipid peroxidation and variations in SOD and CAT activities were observed during the production of lignocellulolytic enzymes and depending on the YE concentrations. The antioxidant defense system was induced in response to the oxidative stress caused by imbalances between the production and the detoxification of ROS.

Effect of the taxonomic group of fungi and type of substrate on the antioxidant activity of a solid-state fermentation system Abstract The enzymatic and non-enzymatic antioxidant activities of a solid-state fermentation system (SSFS) employing six basidiomycete and four ascomycete fungi on orange peel have been evaluated. Class comparisons revealed highly significant effect of fungal group on the antioxidant activity. Peroxidase activity appeared only in the basidiomycete fungi (particularly Pleurotus columbinus, Ganoderma resinaceum, and Pleurotus floridanus) whereas catalase activity appeared in the two fungal groups in favor of the ascomycetes (particularly Paecilomyces variotii and Aspergillus fumigatus). Maximal peroxidase and minimal catalase activities were found at moderate phenolic content, with extreme phenolic levels leading to low peroxidase activity but high catalase activity. Production of the non-enzymatic antioxidants (phenolics, flavonoids, reducing power, and DPPH scavenging) was in favor of the ascomycetes, which showed great native ability to synthesize flavonoids and also to release flavonoids from orange peel. The basidiomycete fungi, which have limited native ability to produce phenolics, had high ability to consume orange peel phenolics. By contrast, the ascomycete fungi exhibited great native ability for production of phenolics and low ability to consume exogenous phenolics.

Combination Therapy of Clinically Approved Antifungal Drugs Is Enhanced by Conjugation with Silver Nanoparticles Abstract Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90–100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.

Wheat storage proteins: changes on the glutenins after wheat infection with different isolates of Fusarium graminearum Abstract Wheat gluten proteins are decisive for the industrial properties of flour, so alterations resulting from grain infection with Fusarium graminearum produce changes in the glutenin content that affect the baking properties. This work analyzes the high-molecular-weight glutenin changes from wheat flour with different degrees of F. graminearum infection at field, since these proteins are determinant for the quality properties of flour. Wheat cultivars—on field trials—infected with F. graminearum isolates of diverse aggressiveness showed severity values between 9.1 and 42.58% and thousand kernel weight values between 28.12 and 32.33 g. Negative correlations between severity and protein content and positive correlations between yield and protein content were observed, employing reversed-phase high-performance liquid chromatography and polyacrylamide gel electrophoresis. Furthermore, the protein signal changes were in agreement for both methodological approaches. Also, the degree of disease observed and the protein changes on infected wheat cultivars varied in relation with the aggressiveness of the isolate responsible for the infection. The principal component analysis showed a close arrangement among protein values obtained by HPLC. For each cultivar, two principal components were obtained, which explained 80.85%, 88.48%, and 93.33% of the total variance (cultivars Sy200, AGP Fast, and Klein Tigre respectively). To our knowledge, the approaches employed for the analysis of protein changes according to the degree of disease, as well as the thorough statistical analysis, are novel for the study of Fusarium Head Blight.

Safety, functional properties and technological performance in whey-based media of probiotic candidates from human breast milk Abstract We aimed at isolating and characterising microorganisms present in human breast milk with probiotic potential. In an 8-week postpartum sampling period, two strains of bifidobacteria (Bifidobacterium longum LM7a and Bifidobacterium dentium LM8a') and four strains of lactobacilli were isolated, all during the first 4-week postpartum. B. longum LM7a and B. dentium LM8a', together with four strains previously isolated from breast milk (Bifidobacterium lactis INL1, INL2, INL4 and INL5), were considered for further studies. Susceptibility of the strains to tetracycline, erythromycin, clindamycin, streptomycin, vancomycin and chloramphenicol was evaluated and the isolates exhibited, in general, the same properties as previously reported for bifidobacteria. All isolates showed low hydrophobicity and B. lactis and B. longum strains had satisfactory resistance to gastric digestion and bile shock, but not to pancreatin. B. lactis INL1, B. longum LM7a and B. dentium LM8a' were selected for some comparative technological studies. In particular, B. lactis INL1 displayed technological potential, with satisfactory growth in cheese whey-based media in biofermentor and resistance to freeze-drying, accelerated storage conditions and simulated gastric digestion.

Isolation and characterization of culturable endophytic bacterial community of stripe rust–resistant and stripe rust–susceptible Pakistani wheat cultivars Abstract In this study, endophytic bacteria isolated from root, stem, and leaf tissues of stripe rust–susceptible (Inqilab 91, Galaxy 2013, and 15BT023) and stripe rust–resistant (NARC 2011, Ujala 2015, TW1410) cultivars were identified and characterized. Abundance of endophytes was found in roots as compared with stems and leaves. Resistant and susceptible cultivars significantly differed in abundance of endophytic bacteria. Restriction analysis of 16S rRNA genes amplified from 100 bacterial isolates produced 17 unique patterns. Representatives of each of the 17 unique patterns were sequenced and identified. Among the sequenced bacteria, 8 belonged to Firmicutes, 7 were Proteobacteria, and 2 were Actinobacteria. Most of the isolates have plant growth–promoting properties and a few have the potential of producing hydrolytic enzymes. Two isolates showed significant inhibition of rust spore germination. These endophytic bacteria not only can be helpful in growth-promoting activities but also can assist in biocontrol of stripe rust disease.

Modulation of laccase transcriptome during biodegradation of naphthalene by white rot fungus Pleurotus ostreatus Abstract Biodegradation of polycyclic aromatic hydrocarbons (PAHs) using Pleurotus ostreatus was investigated in the current study along with the expression levels of laccase genes involved in biodegradation under variable conditions. Biodegradation of PAHs (naphthalene, anthracene, and 1,10-phenanthroline) was detected spectrophotometrically. Recorded data revealed that biodegradation of the tested PAHs was time dependent. Elevated level of naphthalene biodegradation (86.47%) was observed compared to anthracene (27.87%) and 1,10-phenanthroline (24.51%) within 3 days post incubation. Naphthalene was completely degraded within 5 days. Further incubation enhanced the biodegradation of both anthracene and 1,10-phenanthroline until reaches 93.69% and 92.00% biodegradation of the initial concentration within an incubation period of 11 and 14 days, respectively. Naphthalene was selected as a PAH model. HPLC and thin layer chromatography of naphthalene biodegradation products at time intervals proposed that naphthalene was first degraded to α- and β-naphthol which was further metabolized to salicylic and benzoic acid. The metabolic pathway of naphthalene degradation by this fungus was elucidated based on the detected metabolites. The expression profile of six laccase isomers was evaluated using real-time PCR. The transcriptome of the fungal laccase isomers recorded higher levels of transcription under optimized fermentation conditions especially in presence of both naphthalene and Tween 80. The accumulation of such useful metabolites from the biodegradation of PAH pollutants recommended white rot fungus as a potential candidate for production of platform chemicals from PAH wastes.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Natural Language & Linguistic Theory

Idioms, collocations, and structure Abstract Phrasal idioms have been used as evidence in syntactic theorizing for decades. A common assumption, occasionally made explicit (e.g., Larson 2017), is that non-literal phrasal idioms differ significantly from completely literal collocations in the kinds of syntactic structures they can be built from. I show with a detailed empirical study that this is false. In fact, the syntactic constraints on idioms and collocations are identical. In particular, patterns that are missing from one are missing from the other, most strikingly ditransitives with a fixed first object and open second object (*throw the wolves X). Idioms and collocations should therefore be treated the same, as a broad class of conventionalized expressions. I propose a new analysis of the syntactic forms that conventionalized expressions can take. Unlike most previous analyses, I take the open slots to be part of the expression, and the task then becomes to explain the distribution of the open slots. A structural constraint on open slots accounts for the missing ditransitive pattern. It also explains why expressions with a fixed subject but open object are rare, but also why certain examples of this pattern do exist in English and in other languages.

Trisyllabic hypocoristics in Spanish and layered feet Abstract Spanish hypocoristics are usually bisyllabic and sometimes bimoraic. In this paper we study a process of truncation in Spanish that results in trisyllabic hypocoristics (Encárna ← Encarnación, Mariájo ← María José). Trisyllabic hypocoristics usually surface with amphibrach (weak-strong-weak) rhythm (Encárna ← Encarnación), although some forms show anapest (weak-weak-strong) rhythm (Marijó ← María José). This article develops an analysis of this process by means of internally layered ternary feet. Internally layered feet are binary feet to which a weak syllable adjoins to create a minimally recursive foot. The theoretical claim of this paper is twofold: (i) that Spanish trisyllabic truncated forms correspond to an internally layered foot, which reconciles the general assumption that truncated forms maximally correspond to the size of a metrical foot, and (ii) that morphological operations such as truncation can directly refer to internally layered feet, expanding the body of work on layered feet by Martínez-Paricio and Kager (2015). Overall, the analysis presented in this article explores a less studied theoretical and descriptive advantage of this ternary metrical configuration (i.e. its templatic use) and provides new evidence in support of layered feet as a possible metrical representation which emerges in some languages from independently needed constraints.

Perspectives in causal clauses

Whither head movement? Abstract We argue that head movement, as an operation that builds head-adjunction structures in the syntax, has been used to model two empirically distinct classes of phenomena. One class has to do with displacement of heads (fully formed morphological words) to higher syntactic positions, and includes phenomena like verb second and verb initiality. The other class has to do with the construction of complex morphological words and is involved in various types of word formation. Based on the very different clusters of properties associated with these two classes of phenomena, we argue that they each should be accounted for by distinct grammatical operations, applying in distinct modules of the grammar, rather than by the one traditional syntactic head movement operation. We propose that the operation responsible for upward displacement of heads is genuine syntactic movement (Internal Merge) and has the properties of syntactic phrasal movement, including the ability to affect word order, the potential to give rise to interpretive effects, and the locality associated with Internal Merge. On the other hand, word formation is the result of postsyntactic amalgamation, realized as either Lowering (Embick and Noyer 2001) or its upward counterpart, Raising. This operation, we argue, has properties that are not associated with narrow syntax: it is morphologically driven, it results in word formation, it does not exhibit interpretive effects, and it has stricter locality conditions (the Head Movement Constraint). The result is a view of head movement that not only accounts for the empirical differences between the two classes of head movement phenomena, but also lays to rest numerous perennial theoretical problems that have heretofore been associated with the syntactic head adjunction view of head movement. In addition, the framework developed here yields interesting new predictions with respect to the expected typology of head movement patterns.

A processing-based account of subliminal wh-island effects Abstract Wh-island effects are notorious for their cross-linguistic variation. However, experimental syntax studies observed super-additive wh-island effects in some languages which were previously argued to be immune to them. In four acceptability judgment experiments, we investigate the origin of super-additivity in acceptable wh-islands, so-called "subliminal island effects," focusing on Hebrew. Our first experiment reveals a super-additive wh-island effect in Hebrew. However, we suggest that the super-additivity measure for wh-islands is contaminated by processing factors. Specifically, we propose that in this case, the decrease in acceptability reflects interference caused by the simultaneous maintenance of two dependencies, rather than grammatical islandhood. The following experiments demonstrate that super-additivity can be observed in binding structures, where it cannot be attributed to a violation of a grammatical constraint, but rather to processing costs related to interference for maintenance processes. We also show that when minimizing these costs, super-additivity does not emerge in Hebrew wh-islands. We conclude that processing costs underlie the apparent wh-island effect in Hebrew, and perhaps in additional languages, and that the super-additivity paradigm should be fine-tuned in order to avoid these confounds.

Gestural semantics Abstract We argue that a large part of the typology of linguistic inferences can be replicated with gestures, including some that one might not have seen before. While gesture research often focuses on co-speech gestures, which co-occur with spoken words, our study is based on pro-speech gestures (which fully replace spoken words) and post-speech gestures (which follow expressions they modify). We argue that pro-speech gestures can trigger several types of inferences besides entailments: presuppositions and anti-presuppositions (derived from Maximize Presupposition), scalar implicatures and 'Blind Implicatures,' homogeneity inferences that are characteristic of definite plurals, and some expressive inferences that are characteristic of pejorative terms. We further argue that post-speech gestures trigger inferences that are very close to the supplements contributed by appositive relative clauses. We show in each case that we are not dealing with a translation into spoken language because the fine-grained meanings obtained are tied to the iconic properties of the gestures. Our results argue for a generative mechanism that assigns new meanings a specific place in a rich inferential typology, which might have consequences for the structure of semantic theory and the nature of acquisition algorithms.

Templatic morphology as an emergent property Abstract Modern Hebrew exhibits a non-concatenative morphology of consonantal "roots" and melodic "templates" that is typical of Semitic languages. Even though this kind of non-concatenative morphology is well known, it is only partly understood. In particular, theories differ in what counts as a morpheme: the root, the template, both, or neither. Accordingly, theories differ as to what representations learners must posit and what processes generate the eventual surface forms. In this paper I present a theory of morphology and allomorphy that combines lexical roots with syntactic functional heads, improving on previous analyses of root-and-pattern morphology. Verbal templates are here argued to emerge from the combination of syntactic elements, constrained by the general phonology of the language, rather than from some inherent difference between Semitic morphology and that of other languages. This way of generating morphological structure fleshes out a theory of morphophonological alternations that are non-adjacent on the surface but are local underlyingly; with these tools it is possible to identify where lexical exceptionality shows its effects and how it is reined in by the grammar. The Semitic root is thus analogous to lexical roots in other languages, storing idiosyncratic phonological and semantic information but respecting the syntactic structure in which it is embedded.

Verb phrase external arguments in Mande Abstract Mande languages are well-known for their rigid SOVX word order: verb phrases cannot accommodate postpositional phrases, and all oblique arguments must appear after the main verb. This study explores, based on data from Wan (Southeastern Mande), new evidence for syntactic constituency that is essential for developing a formal account of this typologically unusual pattern. First, I show that previously unexplored tonal evidence rules out argument raising accounts. Tone is sensitive in Wan to prosodic phrasing, which is in turn closely related to syntactic constituency; the way postpositional arguments are prosodically integrated into the clause points to their unusually high, clause-level attachment. Second, I argue against a base-generation analysis, which would require a serious modification of the Projection Principle and locality of selection. Third, an analysis based on obligatory extraposition is discussed as the remaining option in transformational frameworks. While accounting for both semantic and tonal evidence, the extraposition account has to rely on a highly unusual kind of filter to rule out all structures where a PP argument appears clause-internally. Accounts postulating such idiosyncratic filters can hardly be considered satisfying, as they merely model constraints on surface structure, without deriving them from underlying structural properties. The obligatory argument extraposition of Mande languages receives a more elegant explanation in constraint-based, surface-oriented theories, which do not need to introduce special devices to handle the basic word order of Mande languages. I illustrate this with a sketch of an account coached in the framework of Lexical-Functional Grammar.

Negation and the functional sequence Abstract There exists a general restriction on admissible functional sequences which prevents adjacent identical heads. We investigate a particular instantiation of this restriction in the domain of negation. Empirically, it manifests itself as a restriction the stacking of multiple negative morphemes. We propose a principled account of this restriction in terms of the general ban on immediately consecutive identical heads in the functional sequence on the one hand, and the presence of a Neg feature inside negative morphemes on the other hand. The account predicts that the stacking of multiple negative morphemes should be possible provided they are separated by intervening levels of structure. We show that this prediction is borne out.

Distinguishing nouns and verbs Abstract Many standard tests for identifying syntactic category, such as distribution and morphological potential, fail to distinguish between nouns and verbs in Tagalog. This state of affairs has led some scholars to propose that Tagalog does not treat verbs as a separate syntactic category from nouns. One such proposal by Kaufman (2009) further argues that adopting this so-called nominalist view of Tagalog allows us to straightforwardly understand a number of facts about the syntax of this language that have so far resisted consensus in analysis. This paper argues that the nominalist view cannot be maintained for Tagalog by showing differential behavior between nominal and verbal constituents in this language. It will furthermore be argued that the nominal behavior exhibited by verbal constituents can be attributed to a pervasive process of nominalization, broadly construed, neutralizing the aforementioned differential behavior. The result of this neutralization is reminiscent of phenomena found in other languages, and raises interesting questions regarding the range of nominalization processes observed cross-linguistically.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Classical Tradition

Stephen Harrison, Victorian Horace: Classics and Class

Brill's Companion to the Reception of Senecan Tragedy: Scholarly, Theatrical and Literary Receptions , Eric Dodson-Robinson (ed.)

Craig Kallendorf, The Protean Virgil. Material Form and the Reception of the Classics

The Publications of the Peplos of Aristotle in the Modern Era

Hindsight as Foresight: Virgilian Retrospective Prophecy in Coopers Hill and The Destruction of Troy Abstract This article discusses how the Virgilian intertexts of the stag hunt in the 1642 edition of Coopers Hill support the interpretation of the passage as a commentary on the trial and execution of the Earl of Strafford, and how they allow Denham to criticize Charles I's involvement in Strafford's death. Despite this criticism, other texts, including Denham's revised (1653/5) edition of the poem, subsequently adapted the stag-hunt episode to commemorate Charles's own trial and execution. The false presentation of the 1653/5 Coopers Hill as an edition that prints an original, authentic version of the poem from 1640 draws on the Virgilian technique of retrospective prophecy to make its status as a commentary on Charles's execution more explicit. Denham repeated this technique in The Destruction of Troy (1656), which heavily revised an excerpt from his 1630s manuscript translation of Aeneid II–VI, and asserts the composition date of this earlier version in order to 'foretell' Charles's execution. Analysing these Virgilian post eventum prophecies shows how both texts simultaneously censure and mourn Charles I, and also identifies increasingly self-recriminatory elements to Denham's own royalism.

"Io ho tutto tradotto fedelmente e senza timore": la Farsaglia di Gaetano Polidori (1841)

'Casual Classicism': In Conversation with Marc Quinn

Reading Suetonius in the Seventeenth Century: The First Political Commentaries

England's Stilicho: Claudian's Political Poetry in Early Modern England

Classics Transformed, ed. Giancarlo Abbamonte and Craig Kallendorf, Pisa: Edizioni ETS, 2018, pp. 164, ISBN: 9788846751683, 20€

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Aesthetic Plastic Surgery

Chinese Facial Beauty Preference

Rigotomy Using Myringotomy Blades Prior to Lipofilling

Invited Response on "Combined Breast Reduction Augmentation"

Invited Discussion on "The Joint Tip Graft: A Joint Support for Rim, Facet and Infratip Lobule in Rhinoplasty"

Invited Commentary on Caudal Septal Extension Graft Sutured with Absorbable Material and Not Fixed to the Nasal Spine Region Compared with the Conventional Fixation Method: A Retrospective Study

Mastopexy Autoaugmentation by Using Vertical and Triangular Flaps of Mammary Parenchyma Through a Vertical Ice Cream Cone-Shaped Approach Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Chondrocutaneous Bilateral Advancement Flap with Postoperative Radiation Therapy for a Helical Rim Keloid Abstract Keloids can be recalcitrant, and a well-planned treatment strategy is essential. Multiple ear piercings have recently become popular, particularly among younger age groups. Management of keloids that develop after piercing of the ear cartilage may be particularly problematic. Helical rim keloids are difficult to excise because of the complex, three-dimensional, cartilaginous structure of the helix and its thin and tightly adherent covering layer of skin. The chondrocutaneous advancement flap introduced by Antia and Buch may be a useful reconstructive option for a helical rim keloid after marginal loss of a segment of the helix as a result of trauma, a burn, or excision of a malignant tumor. However, this technique is limited to wounds that involve only the helix. In this technical note, we describe the use of a chondrocutaneous bilateral advancement flap with postoperative radiation therapy to treat a more invasive and relatively large keloid on the scapha. This technique is straightforward and safe in terms of preserving the blood supply. The addition of adjuvant radiation therapy can help to decrease the risk of recurrence and preserve the morphological structure of the ear and patient satisfaction. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Invited Discussion on: Combined Breast Reduction Augmentation

Combined Breast Reduction Augmentation

Commentary: Endoscopic Transaxillary Versus Inframammary Approaches for Breast Augmentation Using Shaped Implants: A Matched Case–Control Study

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

DNA Repair

Characterization of rare NEIL1 variants found in East Asian populations Publication date: July 2019 Source: DNA Repair, Volume 79 Author(s): Irina G. Minko, Vladimir L. Vartanian, Naoto N. Tozaki, Oskar K. Linde, Pawel Jaruga, Sanem Hosbas Coskun, Erdem Coskun, Chunfeng Qu, Huan He, Chungui Xu, Taoyang Chen, Qianqian Song, Yuchen Jiao, Michael P. Stone, Martin Egli, Miral Dizdaroglu, Amanda K. McCullough, R. Stephen Lloyd Abstract The combination of chronic dietary exposure to the fungal toxin, aflatoxin B1 (AFB1), and hepatitis B viral (HBV) infection is associated with an increased risk for early onset hepatocellular carcinomas (HCCs). An in-depth knowledge of the mechanisms driving carcinogenesis is critical for the identification of genetic risk factors affecting the susceptibility of individuals who are HBV infected and AFB1 exposed. AFB1-induced mutagenesis is characterized by G to T transversions. Hence, the DNA repair pathways that function on AFB1-induced DNA adducts or base damage from HBV-induced inflammation are anticipated to have a strong role in limiting carcinogenesis. These pathways define the mutagenic burden in the target tissues and ultimately limit cellular progression to cancer. Murine data have demonstrated that NEIL1 in the DNA base excision repair pathway was significantly more important than nucleotide excision repair relative to elevated risk for induction of HCCs. These data suggest that deficiencies in NEIL1 could contribute to the initiation of HCCs in humans. To investigate this hypothesis, publicly-available data on variant alleles of NEIL1 were analyzed and compared with genome sequencing data from HCC tissues derived from individuals residing in Qidong County (China). Three variant alleles were identified and the corresponding A51V, P68H, and G245R enzymes were characterized for glycosylase activity on genomic DNA containing a spectrum of oxidatively-induced base damage and an oligodeoxynucleotide containing a site-specific AFB1-formamidopyrimidine guanine adduct. Although the efficiency of the P68H variant was modestly decreased, the A51V and G245R variants showed nearly wild-type activities. Consistent with biochemical findings, molecular modeling of these variants demonstrated only slight local structural alterations. However, A51V was highly temperature sensitive suggesting that its biological activity would be greatly reduced. Overall, these studies have direct human health relevance pertaining to genetic risk factors and biochemical pathways previously not recognized as germane to induction of HCCs.

Regulation of GLI1 by cis DNA elements and epigenetic marks Publication date: July 2019 Source: DNA Repair, Volume 79 Author(s): Robert Taylor, Jun Long, Joon Won Yoon, Ronnie Childs, Kathrine B. Sylvestersen, Michael L. Nielsen, King-Fu Leong, Stephen Iannaccone, David O. Walterhouse, David J. Robbins, Philip Iannaccone Abstract GLI1 is one of three transcription factors (GLI1, GLI2 and GLI3) that mediate the Hedgehog signal transduction pathway and play important roles in normal development. GLI1 and GLI2 form a positive-feedback loop and function as human oncogenes. The mouse and human GLI1 genes have untranslated 5′ exons and large introns 5′ of the translational start. Here we show that Sonic Hedgehog (SHH) stimulates occupancy in the introns by H3K27ac, H3K4me3 and the histone reader protein BRD4. H3K27ac and H3K4me3 occupancy is not significantly changed by removing BRD4 from the human intron and transcription start site (TSS) region. We identified six GLI binding sites (GBS) in the first intron of the human GLI1 gene that are in regions of high sequence conservation among mammals. GLI1 and GLI2 bind all of the GBS in vitro. Elimination of GBS1 and 4 attenuates transcriptional activation by GLI1. Elimination of GBS1, 2, and 4 attenuates transcriptional activation by GLI2. Eliminating all sites essentially eliminates reporter gene activation. Further, GLI1 binds the histone variant H2A.Z. These results suggest that GLI1 and GLI2 can regulate GLI1 expression through protein-protein interactions involving complexes of transcription factors, histone variants, and reader proteins in the regulatory intron of the GLI1 gene. GLI1 acting in trans on the GLI1 intron provides a mechanism for GLI1 positive feedback and auto-regulation. Understanding the combinatorial protein landscape in this locus will be important to interrupting the GLI positive feedback loop and providing new therapeutic approaches to cancers associated with GLI1 overexpression. Graphical abstract

DNA-PKc deficiency drives pre-malignant transformation by reducing DNA repair capacity in concert with reprogramming the epigenome in human bronchial epithelial cells Publication date: July 2019 Source: DNA Repair, Volume 79 Author(s): Ivo Teneng, Maria A. Picchi, Shuguang Leng, Christopher P. Dagucon, Suresh Ramalingam, Carmen S. Tellez, Steven A. Belinsky Abstract The expression of DNA-dependent protein kinase catalytic subunit (DNA-PKc) is highly variable in smokers and reduced enzyme activity has been associated with risk for lung cancer. An in vitro model of lung pre-malignancy was used to evaluate the role of double-strand break DNA repair capacity in transformation of hTERT/CDK4 immortalized human bronchial epithelial cells (HBECs) and reprograming of the epigenome. Here we show that knockdown of DNA-PKc to levels simulating haploinsufficiency dramatically reduced DNA repair capacity following challenge with bleomycin and significantly increased transformation efficiency of HBEC lines exposed weekly for 12 weeks to this radiomimetic. Transformed HBEC lines with wild type or knockdown of DNA-PKc showed altered expression of more than 1,000 genes linked to major cell regulatory pathways involved in lung cancer. While lung cancer driver mutations were not detected in transformed clones, more than 300 genes that showed reduced expression associated with promoter methylation in transformed clones or predictive for methylation in malignant tumors were identified. These studies support reduced DNA repair capacity as a key factor in the initiation and clonal expansion of pre-neoplastic cells and double-strand break DNA damage as causal for epigenetic mediated silencing of many lung cancer-associated genes. The fact that DNA damage, repair, and epigenetic silencing of genes are causal for many other cancers that include colon and prostate extends the generalizability and impact of these findings.

Transcriptional responses to DNA damage Publication date: July 2019 Source: DNA Repair, Volume 79 Author(s): Erica Silva, Trey Ideker Abstract In response to the threat of DNA damage, cells exhibit a dramatic and multi-factorial response spanning from transcriptional changes to protein modifications, collectively known as the DNA damage response (DDR). Here, we review the literature surrounding the transcriptional response to DNA damage. We review differences in observed transcriptional responses as a function of cell cycle stage and emphasize the importance of experimental design in these transcriptional response studies. We additionally consider topics including structural challenges in the transcriptional response to DNA damage as well as the connection between transcription and protein abundance.

Acetylation of Werner protein at K1127 and K1117 is important for nuclear trafficking and DNA repair Publication date: July 2019 Source: DNA Repair, Volume 79 Author(s): Deblina Ghosh, Vilhelm A. Bohr, Parimal Karmakar Abstract Werner syndrome is a rare autosomal recessive disorder where Werner (WRN) gene is mutated. Being a nucleolar protein, during DNA damage, WRN translocates at the damage site where its catalytic function is required in DNA repair. Several studies have indicated that WRN acetylation may modulate WRN trafficking and catalytic function (Blander et al., 2002; Lozada et al., 2014). Among the six acetylation sites in WRN protein identified by mass-spectrometry analysis (Li et al., 2010) we here explore the role of acetylation sites in C-terminal of WRN (K1127, K1117, K1389, K1413) because the C- terminal domain is the hub for protein- protein interaction and DNA binding activity (Brosh et al. [4]; Muftuoglu et al., 2008; Huang et al., 2006). To explore their functional activity, we created mutations in these sites by changing the acetylation residue lysine (K) to a non-acetylation residue arginine (R) and expressed them in WRN mutant cell lines. We observed that K1127R and K1117R mutants are sensitive to the DNA damaging agents etoposide and mitomycin C and display deficient DNA repair. Importantly, deacetylation of WRN by SIRT1 (Mammalian Sir2) is necessary for restoration of WRN localization at nucleoli after completion of DNA repair. Among all putative acetylation sites, K1127R, K1117R and the double mutant K1127R/K1117R showed significantly delayed re-entry to the nucleolus after damage recovery, even when SIRT1 is overexpressed. These mutants showed partial interaction with SIRT1 compared to WT WRN. Thus, our results suggest that K1127 and K1117 are the major sites of acetylation, necessary for DNA repair. These results elucidate the mechanism by which SIRT1 regulates WRN trafficking via these acetylation sites during DNA damage. Graphical abstract

DNA repair in personalized brain cancer therapy with temozolomide and nitrosoureas Publication date: June 2019 Source: DNA Repair, Volume 78 Author(s): Bernd Kaina, Markus Christmann Abstract Alkylating agents have been used since the 60ties in brain cancer chemotherapy. Their target is the DNA and, although the DNA of normal and cancer cells is damaged unselectively, they exert tumor-specific killing effects because of downregulation of some DNA repair activities in cancer cells. Agents exhibiting methylating properties (temozolomide, procarbazine, dacarbazine, streptozotocine) induce at least 12 different DNA lesions. These are repaired by damage reversal mechanisms involving the alkyltransferase MGMT and the alkB homologous protein ALKBH2, and through base excision repair (BER). There is a strong correlation between the MGMT expression level and therapeutic response in high-grade malignant glioma, supporting the notion that O6-methylguanine and, for nitrosoureas, O6-chloroethylguanine are the most relevant toxic damages at therapeutically relevant doses. Since MGMT has a significant impact on the outcome of anti-cancer therapy, it is a predictive marker of the effectiveness of methylating anticancer drugs, and clinical trials are underway aimed at assessing the influence of MGMT inhibition on the therapeutic success. Other DNA repair factors involved in methylating drug resistance are mismatch repair, DNA double-strand break (DSB) repair by homologous recombination (HR) and DSB signaling. Base excision repair and ALKBH2 might also contribute to alkylating drug resistance and their downregulation may have an impact on drug sensitivity notably in cells expressing a high amount of MGMT and at high doses of temozolomide, but the importance in a therapeutic setting remains to be shown. MGMT is frequently downregulated in cancer cells (up to 40% in glioblastomas), which is due to CpG promoter methylation. Astrocytoma (grade III) are frequently mutated in isocitrate dehydrogenase (IDH1). These tumors show a surprisingly good therapeutic response. IDH1 mutation has an impact on ALKBH2 activity thus influencing DNA repair. A master switch between survival and death is p53, which often retains transactivation activity (wildtype) in malignant glioma. The role of p53 in regulating survival via DNA repair and the routes of death are discussed and conclusions as to cancer therapeutic options were drawn.

The mismatch repair-dependent DNA damage response: Mechanisms and implications Publication date: June 2019 Source: DNA Repair, Volume 78 Author(s): Dipika Gupta, Christopher D. Heinen Abstract An important role for the DNA mismatch repair (MMR) pathway in maintaining genomic stability is embodied in its conservation through evolution and the link between loss of MMR function and tumorigenesis. The latter is evident as inheritance of mutations within the major MMR genes give rise to the cancer predisposition condition, Lynch syndrome. Nonetheless, how MMR loss contributes to tumorigenesis is not completely understood. In addition to preventing the accumulation of mutations, MMR also directs cellular responses, such as cell cycle checkpoint or apoptosis activation, to different forms of DNA damage. Understanding this MMR-dependent DNA damage response may provide insight into the full tumor suppressing capabilities of the MMR pathway. Here, we delve into the proposed mechanisms for the MMR-dependent response to DNA damaging agents. We discuss how these pre-clinical findings extend to the clinical treatment of cancers, emphasizing MMR status as a crucial variable in selection of chemotherapeutic regimens. Also, we discuss how loss of the MMR-dependent damage response could promote tumorigenesis via the establishment of a survival advantage to endogenous levels of stress in MMR-deficient cells.

Role of Y-family translesion DNA polymerases in replication stress: Implications for new cancer therapeutic targets Publication date: June 2019 Source: DNA Repair, Volume 78 Author(s): Peter Tonzi, Tony T. Huang Abstract DNA replication stress, defined as the slowing or stalling of replication forks, is considered an emerging hallmark of cancer and a major contributor to genomic instability associated with tumorigenesis (Macheret and Halazonetis, 2015). Recent advances have been made in attempting to target DNA repair factors involved in alleviating replication stress to potentiate genotoxic treatments. Various inhibitors of ATR and Chk1, the two major kinases involved in the intra-S-phase checkpoint, are currently in Phase I and II clinical trials [2]. In addition, currently approved inhibitors of Poly-ADP Ribose Polymerase (PARP) show synthetic lethality in cells that lack double-strand break repair such as in BRCA1/2 deficient tumors [3]. These drugs have also been shown to exacerbate replication stress by creating a DNA-protein crosslink, termed PARP 'trapping', and this is now thought to contribute to the therapeutic efficacy. Translesion synthesis (TLS) is a mechanism whereby special repair DNA polymerases accommodate and tolerate various DNA lesions to allow for damage bypass and continuation of DNA replication (Yang and Gao, 2018). This class of proteins is best characterized by the Y-family, encompassing DNA polymerases (Pols) Kappa, Eta, Iota, and Rev1. While best studied for their ability to bypass physical lesions on the DNA, there is accumulating evidence for these proteins in coping with various natural replication fork barriers and alleviating replication stress. In this mini-review, we will highlight some of these recent advances, and discuss why targeting the TLS pathway may be a mechanism of enhancing cancer-associated replication stress. Exacerbation of replication stress can lead to increased genome instability, which can be toxic to cancer cells and represent a therapeutic vulnerability.

Deciphering the interstrand crosslink DNA repair network expressed by Trypanosoma brucei Publication date: June 2019 Source: DNA Repair, Volume 78 Author(s): Ambika Dattani, Shane R. Wilkinson Abstract Interstrand crosslinks (ICLs) represent a highly toxic form of DNA damage that can block essential biological processes including DNA replication and transcription. To combat their deleterious effects all eukaryotes have developed cell cycle-dependent repair strategies that co-opt various factors from 'classical' DNA repair pathways to resolve such lesions. Here, we report the first systematic dissection of how ICL repair might operate in the Trypanosoma brucei, the causative agent of African trypanosomiasis, and demonstrated that this diverged eukaryote expresses systems that show some intriguing differences to those mechanisms present in other organisms. Following the identification of trypanosomal homologues encoding for CSB, EXO1, SNM1, MRE11, RAD51 and BRCA2, gene deletion coupled with phenotypic studies demonstrated that all the above factors contribute to this pathogen's ICL REPAIRtoire with their activities split across two epistatic groups. We postulate that one network, which encompasses TbCSB, TbEXO1 and TbSNM1, may operate throughout the cell cycle to repair ICLs encountered by transcriptional detection mechanisms while the other relies on homologous recombination enzymes (MRE11, RAD51 and BRCA2) that together help resolve lesions responsible for the stalling of DNA replication forks. This study not only sheds light on the conservation and divergence of ICL repair in one of only a handful of protists that can be studied genetically, but offers the promise of developing or exploiting ICL-causing agents as new anti-parasite therapies.

Transcriptional landscape of DNA repair genes underpins a pan-cancer prognostic signature associated with cell cycle dysregulation and tumor hypoxia Publication date: June 2019 Source: DNA Repair, Volume 78 Author(s): Wai Hoong Chang, Alvina G. Lai Abstract Overactive DNA repair contributes to therapeutic resistance in cancer. However, pan-cancer comparative studies investigating the contribution of all DNA repair genes in cancer progression employing an integrated approach have remained limited. We performed a multi-cohort retrospective analysis to determine the prognostic significance of 138 DNA repair genes in 16 cancer types (n = 16,225). Cox proportional hazards analyses revealed a significant variation in the number of prognostic genes between cancers; 81 genes were prognostic in clear cell renal cell carcinoma while only two genes were prognostic in glioblastoma. We reasoned that genes that were commonly prognostic in highly correlated cancers revealed by Spearman's correlation analysis could be harnessed as a molecular signature for risk assessment. A 10-gene signature, uniting prognostic genes that were common in highly correlated cancers, was significantly associated with overall survival in patients with clear cell renal cell (P < 0.0001), papillary renal cell (P = 0.0007), liver (P = 0.002), lung (P = 0.028), pancreas (P = 0.00013) or endometrial (P = 0.00063) cancers. Receiver operating characteristic analyses revealed that a combined model of the 10-gene signature and tumor staging outperformed either classifier when considered alone. Multivariate Cox regression models incorporating additional clinicopathological features showed that the signature was an independent predictor of overall survival. Tumor hypoxia is associated with adverse outcomes. Consistent across all six cancers, patients with high 10-gene and high hypoxia scores had significantly higher mortality rates compared to those with low 10-gene and low hypoxia scores. Functional enrichment analyses revealed that high mortality rates in patients with high 10-gene scores were attributable to an overproliferation phenotype. Death risk in these patients was further exacerbated by concurrent mutations of a cell cycle checkpoint protein, TP53. The 10-gene signature identified tumors with heightened DNA repair ability. This information has the potential to radically change prognosis through the use of adjuvant DNA repair inhibitors with chemotherapeutic drugs.

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com