bluuebunny/crossref_metadata_2025 huggingface dataset:
Communion and Complaint: Attachment, Object-Relations, and Triangular Love Perspectives on Relationship with God
Authors: Beck Richard
Published: February 2018

The present study attempted to find empirical connections between the attachment, object-relations, and triangular love perspectives as they apply to relationship with God. Attachment to God and object-relations perspectives on God have already been extensively investigated in the literature. In this study, it was observed that the triangular love model (Sternberg, 1986) could also be applied to relationship with God. Using established instruments from each literature—attachment, object-relations, triangular love—it was observed that two factors best explained the correlations among these instruments. The first factor, “Communion,” describes the degree of intimacy, closeness, dependency, and trust in the God-relationship. The second factor, “Complaint,” describes the degree of disappointment and/or frustration involved in the God-relationship. Because these two factors—Communion and Complaint—are orthogonal, it is argued that the commingling of Communion and Complaint in the God-relationship is one feature that can imbue this relationship with an emotional dynamic similar to that observed in human love relationships.
Beyond Survival: Application of a Complex Trauma Treatment Model in the Christian Context
Authors: Pressley Jana , Spinazzola Joseph
Published: February 2018

Disrupted systems of meaning are a core domain in which adults with a complex trauma history are impacted, often leading to adversely affected belief systems. For adult survivors of childhood trauma, experiences related to shame, betrayal, meaning-making, and mourning often complicate their spiritual and/or religious beliefs. This article uses a clinical case example to introduce and illustrate the relevance of a particular complex trauma intervention framework in the context of spiritually-informed treatment with adult Christian clients. Component-Based Psychotherapy (CBP; Hopper, Grossman, Spinazzola, & Zucker, in press) consists of four principal components: (a) relationship, (b) regulation, (c) parts work, and (d) narrative, and is predicated upon the importance of client-therapist parallel process to therapeutic movement and client change. Each treatment component is summarized and practically applied to case material, with particular focus on the ways in which client's faith beliefs and practices can serve as a potential resource and/or barrier in treatment. Particular integrative focus is given to the final treatment component (narrative), where issues of a client's lament, spiritual meaning making, and the therapist's potential vulnerabilities in working with this population are addressed.
Resilience Processes during Cosmology Episodes: Lessons Learned from the Haiti Earthquake
Authors: O'Grady Kari A. , Orton James Douglas
Published: February 2018

The Haiti earthquake of January 2010 serves as an anchor for a new field of research on the role of spirituality in international large-scale catastrophes. Using the case study of one Haitian grandmother affected by the earthquake as a microcosmic representation of the Haitian people, we build an interdisciplinary theory of spirituality in extreme contexts. First, we identify 2 management theory concepts that we found useful: “cosmology episodes” and “sensemaking processes.” Second, through a comparative case study—juxtaposing our findings from the Haiti earthquake of 2010 with Weick's (1993) findings from the Mann Gulch forest fire of 1949—we elaborate on 5 resilience processes that collectively constitute the anatomy of a cosmology episode: anticipating, sense-losing, improvising, sense-remaking, and renewing (or declining). Third, we initiate a more advanced conversation by reinterpreting literature from the psychology of religion and spirituality related to cosmology episodes, by focusing attention on the dynamics of spirituality-imbued transformative pivots within cosmology episodes, and by exploring the role of divine inspiration in cosmology episodes such as the Haiti earthquake. Finally, we call for more interdisciplinary collaboration (e.g., psychology, anthropology, sociology, management, political science, and theology) on the complex topic of the role of spirituality in resilience processes during international cosmology episodes.
A Biblical Analysis of Values Clarification
Authors: Lewis Kathleen N. , Lewis David A.
Published: February 2018

The Values Clarification approach to moral education is examined and evaluated in this article in light of biblical teachings and principles as understood by evangelical Christians. Its basic assumptions and primary techniques are identified and the possible negative effects of its strategies indicated. Values Clarification morality, it is concluded, promotes situational ethics, humanistic over-optimism about human nature, and unreasoned decision-making. At root is a de facto denial of the existence of any set of God-given standards or absolutes as guides for right or wrong behavior.
Juxtaposing the Brain and Belief
Authors: Ashbrook James B.
Published: February 2018

To juxtapose the brain and belief sheds new light on puzzling patterns of belief. The brain works in two ways: a stabilizing step-by-step process and a variety-generating all-at-once process. Patterns of belief also present two kinds of focal meaning: setting-right of reality through the interpretations and imperatives of the proclamation of the Gospel and making-real of reality through the experiences and symbolizations of God's manifestations of himself. “Mind” provides an analytic metaphor which relates these processes of the brain and patterns of belief. As an organized whole, the brain reveals regularities. As part of a larger whole, the mind generates emergent features. Just as the mind is the human meaning of the brain, so God is the theological referent of the mind. The goodness and sovereignty of God are reflected in our one brain with its two ways of working. That which is most fully “us” is that which is most truly “real.”
Women in Missions: A Pilot Study
Authors: Beck James R.
Published: February 2018

Women have been and are a vital force in the North American missionary movement In this study an attempt is made to identify trends in the background and training of women currently being sent abroad as compared with those who went overseas thirty years ago. Data were collected comparing 1951–53 appointees with 1981–83 appointees on their levels of education, age, family background, spiritual experience, and other factors. Statistically significant differences between the two groups emerged on age, marital status, exposure to psychotherapy, cross cultural exposure, and family background. The study concludes with a discussion of how these results affect recruitment decisions by mission executives.
Christian Anti-Psychology and the Scientific Method
Authors: Foster James D. , Ledbetter Mark F.
Published: February 2018

Christians are becoming increasingly vocal in their criticism of scientific psychology. In their criticisms Christian anti-psychologists have devalued knowledge gained through research and suggested both that the scientific method is inappropriate for studying human behavior and that the deception inherent in psychological research is immoral. This article examines these concerns and argues that the more subjective alternatives suggested by the critics of psychology suffer from many of the same limitations as scientific psychology and that taking such an approach would amount to substituting uncontrolled error for controlled error and uncontrolled deception for controlled deception.
Theology and Psychological Theory: Psychological Implications of Some Modern Theologies
Authors: Spilka Barnard , Bridges Robert A.
Published: February 2018

In a sense, theologies are psychologies. They discuss the human condition, largely in terms of motivation and cognition, and suggest ways of organizing our thinking about human aspirations and goals. These considerations are nowhere more evident than in contemporary process, liberation, and feminist theologies. This article shows parallels among these perspectives relative to modern psychological research and theory, primarily in social psychology and more particularly relative to social cognition theory. The importance of the role of the self and needs for meaning, control, and self-esteem are stressed, indicating that theology can serve as psychological theory and that both psychology and theology might benefit from increased interaction between the disciplines.
Isomorphic Indicators in Theological and Psychological Science
Authors: Anderson Ray S.
Published: February 2018

The culture split between science and theology by which theology tends to abandon the concrete observable world to science, while science tends to dismiss questions of ontology (God), is presented as a framework within which to examine the preceding articles in this issue. The inadequacy of attempting to bridge this dichotomy by constructing a synthesis between psychology and theology on the common ground of religious experience is shown. An alternative approach to theology as having its focus on the interaction between the human self, others and God is presented, suggesting that a convergence between theology and psychology can be found in their common interest in the nature of the human self as being-in-becoming. This convergence is examined as an isomorphic structure where, despite different “ancestry,” theology and psychology attempt to explain and give meaning to human experience as grounded in being (ontology), experienced in a knowing way (epistemology), and open to change by the reality of transcendent being which moves the self toward goals which offer healing and hope (teleology).
The heart is where the battle is: an interview with A. Sivanandan
Authors: Sivanandan A.
Published: February 2018

A. Sivanandan, director of the Institute of Race Relations for over thirty years and the Founding Editor of Race & Class, has died. We publish below an interview with him, which prefaced the second collection of his writings Communities of Resistance: writings on black struggles for socialism (Verso, 1990), and which has not before appeared in the journal. In it, Sivanandan recounts his early life and education in the then colonial Ceylon, and the forces that shaped his politics, his poetry of language and thought, and his embrace of dialectical materialism. This was not just at the cerebral level but, more importantly and significantly, at the deepest personal level and, in this, it informed a profound and visionary activism that continued undaunted till his death. Crucial to the trajectory of his life was the experience of leaving the anti-Tamil riots in Ceylon and walking into the 1958 anti-black riots in Notting Hill, a ‘double baptism of fire’. The interview explicates the significance of the transformation that he spearheaded and, with IRR staff and members, fought for, of the Institute of Race Relations. In the process, an elitist government-orientated body became one that spoke from the vantage point of those at the sharpest end of racist exploitation and oppression. That transformation in itself exemplified the issues of race and class and their relationship that Sivanandan explored so fruitfully and with so much personal and political energy in all his writings and interventions. Out of it, and his thinking and principles, this journal was born.
A methodology for mapping native and invasive vegetation coverage in archipelagos
Authors: Rivas-Torres Gonzalo F , Benítez Fátima L , Rueda Danny , Sevilla Christian , Mena Carlos F
Published: February 2018

This study develops a mixed, systematic, low-cost methodology to define and map native vegetation and the spread of the most aggressive invasive species in islands biomes, focusing on the Galápagos National Park (GNP). Based on preliminary legends defined by experts, Landsat 8/OLI fusion imagery was used for object-oriented classification to obtain the vegetation map of this archipelago. This technique was later verified and validated using high-resolution images from unmanned aerial vehicles (UAVs, i.e., drones) and dedicated satellites, ground truthing, and visual confirmation around GNP coasts. This mixed methodology allowed mapping of nine native ecosystems, six invasive-dominated vegetation units, and two types of lavas. Around 53.63% of GNP is covered by native ecosystems and ∼2.2% is “canopy” dominated by invasive species to date. Native-dominated deciduous forest types cover ∼40.8% of the GNP and only ∼12.8% of the protected area is nowadays covered by humid and transitional type native ecosystems. Among humid native ecosystems, those distributed in the highlands only cover 4.8% and are highly threatened by invasive species, which are mostly distributed in these summit areas. Of the five islands (out of 18) recording invasive-dominated units, Isabela and Santa Cruz were the most infested. Cedrela odorata, Pennisetum purpureum, and Psidium guajava were the main invasive plants dominating the GNP canopy. Highly noxious Rubus niveus was the only invasive species dominating areas among the five infested islands. Methodology detailed here proved useful to provide accurate spatially-explicit islands vegetation data, potential for replication in time, and is expected to aid suitable management of highly endangered and unique biotas in this and other tropical island biomes.
Comparison of the in vitro toxicological activity of various particulate matter
Authors: Cho Hyun-Ki , Park Chang-Gyun , Shin Han-Jae , Park Ki-Hong , Lim Heung-Bin
Published: February 2018

Ultrafine particles (UFPs, < 2.5 µm) in air pollutants have been identified as a major cause of respiratory diseases, since they can affect the lung alveoli through the bronchus. In particular, if toxicants such as heavy metals and polycyclic aromatic hydrocarbons (PAHs) are present in UFPs, they can cause diseases such as asthma, chronic obstructive pulmonary disease, and lung cancer. This study compared in vitro toxicity of various particulate matter including UFPs from combustion particles of diesel (diesel exhaust particles (DEP)), rice straw (RS), pine stem (PS) and coal (CC), and road dust particles from tunnel (TD) and roadside (RD). UFPs from combustion particles and road dust were collected with a glass fiber filter using burning systems and a solid aerosol generator. Cell viability was determined by neutral red uptake assay using Chinese hamster ovary strain K1 cells. Redox cycling activity and intracellular reactive oxygen species were measured using 1,4-dithiothreitol (DTT) and 2′,7′-dichlorofluorescin diacetate (DCF-DA) assay, respectively. Our in vitro studies validated that combustion particles had high toxicological activity. PS demonstrated the highest activity in cytotoxicity but DEP had the highest activity in the DTT and DCF-DA assays. Overall, since the toxicological activity of particles generated by various means was different, risk assessment should be conducted through various toxicity evaluations rather than one toxicity evaluation.
Psychological and physical violence towards children with disabilities in Finland and Sweden
Authors: Koivula Tanja , Ellonen Noora , Janson Staffan , Jernbro Carolina , Huhtala Heini , Paavilainen Eija
Published: February 2018

This article describes psychological aggression and physical violence by Swedish and Finnish mothers ( N = 3420) towards their 0- to 12-year-old children with disabilities ( N = 286) by comparing such behaviour with the mothers of children without disabilities ( N = 3134). The survey data are based on representative samples from Finland and Sweden of mothers’ reports of their behaviour towards their child in conflict situations. Mothers of children with disabilities reported more psychological aggression towards their child than did mothers of children without disabilities. Mothers used psychological aggression, especially towards children with neurological/psychological disabilities. However, the only significant difference regarding physical violence was repetitive use of mild physical violence. Overall, the analysis suggests that children with neurological/psychological disabilities are more exposed to both psychological and physical violence than children without disabilities or children with somatic/developmental disabilities.
Methodological reflections on the use of systematic reviews in early childhood research
Authors: Ang Lynn
Published: February 2018

This article sets out to look critically at the use of systematic reviews in the cross-disciplinary field of early childhood and international development. Systematic reviews – a specialist methodology involving the secondary analysis of existing knowledge on a particular topic – is prevalently used to address complex questions in social and health-related policy and is an established tradition in the life and health sciences. In education and the social sciences, there is burgeoning interest in systematic methodological approaches, although its usage remains comparatively lagging compared to the medical field. Drawing on an interdisciplinary systematic review of empirical research on early childhood development and peacebuilding in the Asia Pacific region, this article reflects on the use of the methodology and its potential to inform new conceptual and methodological developments. The article argues that our knowledge of children and the early years can be significantly advanced by furthering debates on systematic reviews particularly in cross-disciplinary fields and its application, as well as relevance for how evidence is evaluated and applied. This is especially pertinent in a sector driven by increasing calls for more reliable and timely information to influence practice and policy decision-making.
Multi-objective pose optimal distribution method for the feed support system of Five-hundred-meter Aperture Spherical radio Telescope
Authors: Deng Sai , Jing Fengshui , Zheng Rongzhang , Liang Zize , Yang Guodong
Published: February 2018

The Five-hundred-meter Aperture Spherical radio Telescope is the world’s largest single-dish radio telescope and is located in the southwest of China. The cable-driven parallel robot and A-B rotator of the feed support system in Five-hundred-meter Aperture Spherical radio Telescope are designed to realize the theoretical position and attitude of the receiver. The feed support system is a pose-redundant and rigid–flexible coupling system; thus, the method of pose distribution between the A-B rotator and the cable-driven parallel robot impacts on the cable tension distribution and stiffness of the feed support system, which are crucial to the feed support system stability. The main purpose of this study is to examine the pose optimal distribution method for the feed support system. First, a mechanical model of the feed support system, which considers the time-varying barycenter of the feed cabin and the back-illuminated strategy of the receiver, is established. Then, a pose distribution method that ensures the position and attitude accuracy of the receiver is proposed for the feed support system. Considering the performance indices of the variance of cable tensions and the stiffness of the cable-driven parallel robot, an optimization of the rotation angles of the A-B rotator with multiple objectives is implemented using a genetic algorithm. Finally, simulations are conducted to demonstrate the effectiveness of the proposed method compared with others. Results show that the proposed approach not only ensures the attitude accuracy of the receiver but also maintains the lower variance of cable tensions and higher stiffness of the feed support system.
Enriching classroom learning through a microblogging-supported activity
Authors: Li Kun , Darr Kent , Gao Fei
Published: February 2018

Researchers have recognized the role that microblogging tools play in enhancing the effectiveness of communication and interaction in the classroom. However, few studies have specifically examined how to use microblogging tools to bring educational resources into the classroom to enrich the student learning experience. The exploratory case study examined an instructional activity designed to expand and deepen student learning experience by having undergraduate students subscribe to, read, and share tweets from high-quality Twitter accounts in the field. The findings suggested that students believed that the activity broadened their knowledge on the topics to be learned, helped them see the connections between coursework and real work, and empowered them with a new tool for learning and inquiry.
Effect of knit and print parameters on peel strength of hybrid 3-D printed textiles
Authors: Narula Ayushi , Pastore Christopher M , Schmelzeisen David , El Basri Sara , Schenk Jan , Shajoo Subin
Published: February 2018

The influence of knit fabric structure on the adhesion of three-dimensional (3-D) printed textiles was examined. 3-D printing was applied to different elastic knitted fabrics with different amounts of prestretch, typical for 4-D fabric construction. The quality of the bond was measured in terms of peel strength. Peel strength was measured by pulling the fabric at 180° from the printed plastic to delaminate the 2 and recording the 10 highest peak values observed during the test. The printed width, the ratio of fabric width of print width, fabric washing, and fabric structure were varied. The specimens were then evaluated for peel strength.
A primary role for human central memory cells in tissue immunosurveillance
Authors: Gehad Ahmed , Teague Jessica E. , Matos Tiago R. , Huang Victor , Yang Chao , Watanabe Rei , O’Malley John T. , Trimble Cornelia L. , Kupper Thomas S. , Clark Rachael A.
Published: February 2018

Key Points

Human TCM are tissue tropic, have impressive effector functions, and are found in noninflamed human tissues. TCM can act alone to induce inflammation in human skin–grafted mice; results suggest a role for human TCM in primary immunosurveillance.
Haploidentical HSCT for hemoglobinopathies: improved outcomes with TCRαβ+/CD19+-depleted grafts
Authors: Gaziev Javid , Isgrò Antonella , Sodani Pietro , Paciaroni Katia , De Angelis Gioia , Marziali Marco , Ribersani Michela , Alfieri Cecilia , Lanti Alessandro , Galluccio Tiziana , Adorno Gaspare , Andreani Marco
Published: February 2018

Key Points

TCRαβ+/CD19+-depleted haplo-HCT is associated with a reduced incidence of graft failure in patients with hemoglobinopathies. The major challenges of haplo-HCT in hemoglobinopathies are delayed immune reconstitution and associated morbidity and mortality.
Indoor bacteria and asthma in adults: a multicentre case–control study within ECRHS II
Authors: Pekkanen Juha , Valkonen Maria , Täubel Martin , Tischer Christina , Leppänen Hanna , Kärkkäinen Päivi M. , Rintala Helena , Zock Jan-Paul , Casas Lidia , Probst-Hensch Nicole , Forsberg Bertil , Holm Mathias , Janson Christer , Pin Isabelle , Gislason Thorarinn , Jarvis Debbie , Heinrich Joachim , Hyvärinen Anne
Published: February 2018

Both protective and adverse effects of indoor microbial exposure on asthma have been reported, but mostly in children. To date, no study in adults has used non-targeted methods for detection of indoor bacteria followed by quantitative confirmation.

A cross-sectional study of 198 asthmatic and 199 controls was conducted within the European Community Respiratory Health Survey (ECRHS) II. DNA was extracted from mattress dust for bacterial analysis using denaturing gradient gel electrophoresis (DGGE). Selected bands were sequenced and associations with asthma confirmed with four quantitative PCR (qPCR) assays.

15 out of 37 bands detected with DGGE, which had at least a suggestive association (p<0.25) with asthma, were sequenced. Of the four targeted qPCRs,Clostridiumcluster XI confirmed the protective association with asthma. The association was dose dependent (aOR 0.43 (95% CI 0.22–0.84) for the fourthversusfirst quartile, p for trend 0.009) and independent of other microbial markers. Few significant associations were observed for the three other qPCRs used.

In this large international study, the level ofClostridiumcluster XI was independently associated with a lower risk of prevalent asthma. Results suggest the importance of environmental bacteria also in adult asthma, but need to be confirmed in future studies.
Macitentan in pulmonary hypertension due to left ventricular dysfunction
Authors: Vachiéry Jean-Luc , Delcroix Marion , Al-Hiti Hikmet , Efficace Michela , Hutyra Martin , Lack Gabriela , Papadakis Kelly , Rubin Lewis J.
Published: February 2018

The MELODY-1 study evaluated macitentan for pulmonary hypertension because of left heart disease (PH-LHD) in patients with combined post- and pre-capillary PH.

63 patients with PH-LHD and diastolic pressure gradient ≥7 mmHg and pulmonary vascular resistance (PVR) >3WU were randomised to macitentan 10 mg (n=31) or placebo (n=32) for 12 weeks. The main end-point assessed a composite of significant fluid retention (weight gain ≥5% or ≥5 kg because of fluid overload or parenteral diuretic administration) or worsening in New York Heart Association functional class from baseline to end of treatment. Exploratory end-points included changes in N-terminal pro-brain natriuretic peptide (NT-proBNP) and haemodynamics at week 12.

Seven macitentan-treated and four placebo-treated patients experienced significant fluid retention/worsening functional class; treatment difference, 10.08% (95% CI −15.07–33.26; p=0.34). The difference, driven by the fluid retention component, was apparent within the first month. At week 12,versusplacebo, the macitentan group showed no change in PVR, mean right atrial pressure or pulmonary arterial wedge pressure; a non-significant increase in cardiac index (treatment effect 0.4 (95% CI 0.1–0.7) L·min−1·m−2) and decrease in NT-proBNP (0.77 (0.55–1.08)) was observed. Adverse events and serious adverse events were numerically more frequent with macitentanversusplacebo.

Macitentan-treated patients were quantitatively more likely to experience significant fluid retentionversusplacebo. Macitentan resulted in no significant changes in any exploratory end-points.
Neutrophil to lymphocyte ratio and clinical outcomes in COPD: recent evidence and future perspectives
Authors: Paliogiannis Panagiotis , Fois Alessandro G. , Sotgia Salvatore , Mangoni Arduino A. , Zinellu Elisabetta , Pirina Pietro , Negri Silvia , Carru Ciriaco , Zinellu Angelo
Published: February 2018

Chronic obstructive pulmonary disease (COPD) is a disabling condition that is characterised by poorly reversible airflow limitation and inflammation. Acute exacerbations of COPD are a common cause of hospitalisation and death among COPD patients. Several biochemical markers have been studied as outcome predictors in COPD; however, their measurement often requires significant time and resources. Relatively simple biomarkers of inflammation calculated from routine complete blood count tests, such as the neutrophil to lymphocyte ratio (NLR), might also predict COPD progression and outcomes. This review discusses the available evidence from studies investigating the associations between the NLR, COPD exacerbations and death in this patient group.
Neurogenic differentiation by hippocampal neural stem and progenitor cells is biased by NFIX expression
Authors: Harris Lachlan , Zalucki Oressia , Clément Olivier , Fraser James , Matuzelski Elise , Oishi Sabrina , Harvey Tracey J. , Burne Thomas H. J. , Heng Julian Ik-Tsen , Gronostajski Richard M. , Piper Michael
Published: February 2018

Our understanding of the transcriptional programme underpinning adult hippocampal neurogenesis is incomplete. In mice, under basal conditions, adult hippocampal neural stem cells (AH-NSCs) generate neurons and astrocytes, but not oligodendrocytes. The factors limiting oligodendrocyte production, however, remain unclear. Here, we reveal that the transcription factor NFIX plays a key role in this process. NFIX is expressed by AH-NSCs, and its expression is sharply upregulated in adult hippocampal neuroblasts. Conditional ablation of Nfix from AH-NSCs, coupled with lineage tracing, transcriptomic sequencing and behavioural studies collectively reveal that NFIX is cell-autonomously required for neuroblast maturation and survival. Moreover, a small number of AH-NSCs also develop into oligodendrocytes following Nfix deletion. Remarkably, when Nfix is deleted specifically from intermediate progenitor cells and neuroblasts using a Dcx-creERT2 driver, these cells also display elevated signatures of oligodendrocyte gene expression. Together, these results demonstrate the central role played by NFIX in neuroblasts within the adult hippocampal stem cell neurogenic niche in promoting the maturation and survival of these cells, while concomitantly repressing oligodendrocyte gene expression signatures.
A genetically encoded fluorescent probe for imaging of oxygenation gradients in living Drosophila
Authors: Lidsky Peter V. , Lukyanov Konstantin A. , Misra Tvisha , Handke Björn , Mishin Alexander S. , Lehner Christian F.
Published: February 2018

Oxygen concentrations vary between tissues of multicellular organisms and change under certain physiological or pathological conditions. Multiple methods have been developed for measuring oxygenation of biological samples in vitro and in vivo. However, most require complex equipment, are laborious and have significant limitations. Here we report that oxygen concentration determines the choice between two maturation pathways of DsRed FT (Timer). At high oxygen levels, this DsRed derivate matures predominantly into a red fluorescent isoform. By contrast, a green fluorescent isoform is favored by low oxygen levels. Ratiometric analysis of green and red fluorescence after a pulse of Timer expression in Drosophila larvae provides a record of the history of tissue oxygenation during a subsequent chase period, for the whole animal with single-cell precision. Tissue spreads revealed fine differences in oxygen exposure among different cells of the same organ. We expect that the simplicity and robustness of our approach will greatly impact hypoxia research, especially in small animal models.
ES cell-derived presomitic mesoderm-like tissues for analysis of synchronized oscillations in the segmentation clock
Authors: Matsumiya Marina , Tomita Takehito , Yoshioka-Kobayashi Kumiko , Isomura Akihiro , Kageyama Ryoichiro
Published: February 2018

Somites are periodically formed by segmentation of the anterior parts of the presomitic mesoderm (PSM). In the mouse embryo, this periodicity is controlled by the segmentation clock gene Hes7, which exhibits wave-like oscillatory expression in the PSM. Despite intensive studies, the exact mechanism of such synchronous oscillatory dynamics of Hes7 expression still remains to be analyzed. Detailed analysis of the segmentation clock has been hampered because it requires the use of live embryos, and establishment of an in vitro culture system would facilitate such analyses. Here, we established a simple and efficient method to generate mouse ES cell-derived PSM-like tissues, in which Hes7 expression oscillates like traveling waves. In these tissues, Hes7 oscillation is synchronized between neighboring cells, and the posterior-anterior axis is self-organized as the central-peripheral axis. This method is applicable to chemical-library screening and will facilitate the analysis of the molecular nature of the segmentation clock.
The ELMO-MBC complex and RhoGAP19D couple Rho family GTPases during mesenchymal-to-epithelial-like transitions
Authors: Toret Christopher P. , Shivakumar Pruthvi C. , Lenne Pierre-François , Le Bivic Andre
Published: February 2018

Many metazoan developmental processes require cells to transition between migratory mesenchymal- and adherent epithelial-like states. These transitions require Rho GTPase-mediated actin rearrangements downstream of integrin and cadherin pathways. A regulatory toolbox of GEF and GAP proteins precisely coordinates Rho protein activities, yet defining the involvement of specific regulators within a cellular context remains a challenge due to overlapping and coupled activities. Here, we demonstrate that Drosophila dorsal closure is a powerful model for Rho GTPase regulation during transitions from leading edges to cadherin contacts. During these transitions, a Rac GEF ELMO-MBC complex regulates both lamellipodia and Rho1-dependent, actomyosin-mediated tension at initial cadherin contacts. Moreover, the Rho GAP RhoGAP19D controls Rac and Rho GTPases during the same processes and genetically regulates the ELMO-MBC complex. This study presents a fresh framework with which to understand the inter-relationship between GEF and GAP proteins that tether Rac and Rho cycles during developmental processes.
Face morphogenesis is promoted by Pbx-dependent EMT via regulation of Snail1 during frontonasal prominence fusion
Authors: Losa Marta , Risolino Maurizio , Li Bingsi , Hart James , Quintana Laura , Grishina Irina , Yang Hui , Choi Irene F. , Lewicki Patrick , Khan Sameer , Aho Robert , Feenstra Jennifer , Vincent C. Theresa , Brown Anthony M. C. , Ferretti Elisabetta , Williams Trevor , Selleri Licia
Published: February 2018

Human cleft lip with or without cleft palate (CL/P) is a common craniofacial abnormality caused by impaired fusion of the facial prominences. We have previously reported that, in the mouse embryo, epithelial apoptosis mediates fusion at the seam where the prominences coalesce. Here, we show that apoptosis alone is not sufficient to remove the epithelial layers. We observed morphological changes in the seam epithelia, intermingling of cells of epithelial descent into the mesenchyme and molecular signatures of epithelial-mesenchymal transition (EMT). Utilizing mouse lines with cephalic epithelium-specific Pbx loss exhibiting CL/P, we demonstrate that these cellular behaviors are Pbx dependent, as is the transcriptional regulation of the EMT driver Snail1. Furthermore, in the embryo, the majority of epithelial cells expressing high levels of Snail1 do not undergo apoptosis. Pbx1 loss- and gain-of-function in a tractable epithelial culture system revealed that Pbx1 is both necessary and sufficient for EMT induction. This study establishes that Pbx-dependent EMT programs mediate murine upper lip/primary palate morphogenesis and fusion via regulation of Snail1. Of note, the EMT signatures observed in the embryo are mirrored in the epithelial culture system.
Mesenchymal Wnt/β-catenin signaling limits tooth number
Authors: Järvinen Elina , Shimomura-Kuroki Junko , Balic Anamaria , Jussila Maria , Thesleff Irma
Published: February 2018

Tooth agenesis is one of the predominant developmental anomalies in humans, usually affecting the permanent dentition generated by sequential tooth formation and, in most cases, caused by mutations perturbing epithelial Wnt/β-catenin signaling. In addition, loss-of-function mutations in the Wnt feedback inhibitor AXIN2 lead to human tooth agenesis. We have investigated the functions of Wnt/β-catenin signaling during sequential formation of molar teeth using mouse models. Continuous initiation of new teeth, which is observed after genetic activation of Wnt/β-catenin signaling in the oral epithelium, was accompanied by enhanced expression of Wnt antagonists and a downregulation of Wnt/β-catenin signaling in the dental mesenchyme. Genetic and pharmacological activation of mesenchymal Wnt/β-catenin signaling negatively regulated sequential tooth formation, an effect partly mediated by Bmp4. Runx2, a gene whose loss-of-function mutations result in sequential formation of supernumerary teeth in the human cleidocranial dysplasia syndrome, suppressed the expression of Wnt inhibitors Axin2 and Drapc1 in dental mesenchyme. Our data indicate that increased mesenchymal Wnt signaling inhibits the sequential formation of teeth, and suggest that Axin2/Runx2 antagonistic interactions modulate the level of mesenchymal Wnt/β-catenin signaling, underlying the contrasting dental phenotypes caused by human AXIN2 and RUNX2 mutations.
Lsd1 interacts with cMyb to demethylate repressive histone marks and maintain inner ear progenitor identity
Authors: Ahmed Mohi , Streit Andrea
Published: February 2018

During development, multipotent progenitor cells must maintain their identity while retaining the competence to respond to new signalling cues that drive cell fate decisions. This depends on both DNA-bound transcription factors and surrounding histone modifications. Here, we identify the histone demethylase Lsd1 as a crucial component of the molecular machinery that preserves progenitor identity in the developing ear prior to lineage commitment. Although Lsd1 is mainly associated with repressive complexes, we show that, in ear precursors, it is required to maintain active transcription of otic genes. We reveal a novel interaction between Lsd1 and the transcription factor cMyb, which in turn recruits Lsd1 to the promoters of key ear transcription factors. Here, Lsd1 prevents the accumulation of repressive H3K9me2, while allowing H3K9 acetylation. Loss of Lsd1 function causes rapid silencing of active promoters and loss of ear progenitor genes, and shuts down the entire ear developmental programme. Our data suggest that Lsd1-cMyb acts as a co-activator complex that maintains a regulatory module at the top of the inner ear gene network.
F-box proteins Pof3 and Pof1 regulate Wee1 degradation and mitotic entry in fission yeast
Authors: Qiu Cui , Yi Yuan-yuan , Lucena Rafael , Wu Meng-juan , Sun Jia-hao , Wang Xi , Jin Quan-wen , Wang Yamei
Published: February 2018

The key cyclin-dependent kinase Cdk1 (Cdc2) promotes irreversible mitotic entry, mainly by activating the phosphatase Cdc25 while suppressing the tyrosine kinase Wee1. Wee1 needs to be downregulated at the onset of mitosis to ensure rapid activation of Cdk1. In human somatic cells, one mechanism of suppressing Wee1 activity is mediated by ubiquitylation-dependent proteolysis through the Skp1/Cul1/F-box protein (SCF) ubiquitin E3 ligase complex. This mechanism is believed to be conserved from yeasts to humans. So far, the best-characterized human F-box proteins involved in recognition of Wee1 are β-TrCP (BTRCP) and Tome-1 (CDCA3). Although fission yeast Wee1 was the first identified member of its conserved kinase family, the F-box proteins involved in recognition and ubiquitylation of Wee1 have not been identified in this organism. In this study, our screen using Wee1–Renilla luciferase as the reporter revealed that two F-box proteins, Pof1 and Pof3, are required for downregulating Wee1 and are possibly responsible for recruiting Wee1 to SCF. Our genetic analyses supported a functional relevance between Pof1 and Pof3 and the rate of mitotic entry, and Pof3 might play a major role in this process.
Non-equivalence of nuclear import among nuclei in multinucleated skeletal muscle cells
Authors: Cutler Alicia A. , Jackson Jennifer B. , Corbett Anita H. , Pavlath Grace K.
Published: February 2018

Skeletal muscle is primarily composed of large myofibers containing thousands of post-mitotic nuclei distributed throughout a common cytoplasm. Protein production and localization in specialized myofiber regions is crucial for muscle function. Myonuclei differ in transcriptional activity and protein accumulation, but how these differences among nuclei sharing a cytoplasm are achieved is unknown. Regulated nuclear import of proteins is one potential mechanism for regulating transcription spatially and temporally in individual myonuclei. The best-characterized nuclear localization signal (NLS) in proteins is the classical NLS (cNLS), but many other NLS motifs exist. We examined cNLS and non-cNLS reporter protein import using multinucleated muscle cells generated in vitro, revealing that cNLS and non-cNLS nuclear import differs among nuclei in the same cell. Investigation of cNLS nuclear import rates in isolated myofibers ex vivo confirmed differences in nuclear import rates among myonuclei. Analyzing nuclear import throughout myogenesis revealed that cNLS and non-cNLS import varies during differentiation. Taken together, our results suggest that both spatial and temporal regulation of nuclear import pathways are important in muscle cell differentiation and protein regionalization in myofibers.
Tight junctions negatively regulate mechanical forces applied to adherens junctions in vertebrate epithelial tissue
Authors: Hatte Guillaume , Prigent Claude , Tassan Jean-Pierre
Published: February 2018

Epithelia are layers of polarised cells tightly bound to each other by adhesive contacts. Epithelia act as barriers between an organism and its external environment. Understanding how epithelia maintain their essential integrity while remaining sufficiently plastic to allow events such as cytokinesis to take place is a key biological problem. In vertebrates, the remodelling and reinforcement of adherens junctions maintains epithelial integrity during cytokinesis. The involvement of tight junctions in cell division, however, has remained unexplored. Here, we examine the role of tight junctions during cytokinesis in the epithelium of the Xenopus laevis embryo. Depletion of the tight junction-associated proteins ZO-1 and GEF-H1 leads to altered cytokinesis duration and contractile ring geometry. Using a tension biosensor, we show that cytokinesis defects originate from misregulation of tensile forces applied to adherens junctions. Our results reveal that tight junctions regulate mechanical tension applied to adherens junctions, which in turn impacts cytokinesis.

This article has an associated First Person interview with the first author of the paper.
The ARF guanine nucleotide exchange factor GBF1 is targeted to Golgi membranes through a PIP-binding domain
Authors: Meissner Justyna M. , Bhatt Jay M. , Lee Eunjoo , Styers Melanie L. , Ivanova Anna A. , Kahn Richard A. , Sztul Elizabeth
Published: February 2018

ADP-ribosylation factors (ARF) GTPases are activated by guanine nucleotide exchange factors (GEFs) to support cellular homeostasis. Key to understanding spatio-temporal regulation of ARF signaling is the mechanism of GEF recruitment to membranes. Small GEFs are recruited through phosphoinositide (PIP) binding by a pleckstrin homology (PH) domain downstream from the catalytic Sec7 domain (Sec7d). The large GEFs lack PH domains, and their recruitment mechanisms are poorly understood. We probed Golgi recruitment of GBF1, a GEF catalyzing ARF activation required for Golgi homeostasis. We show that the homology downstream of Sec7d-1 (HDS1) regulates Golgi recruitment of GBF1. We document that GBF1 binds phosphoinositides, preferentially PI3P, PI4P and PI(4,5)P2, and that lipid binding requires the HDS1 domain. Mutations within HDS1 that reduce GBF1 binding to specific PIPs in vitro inhibit GBF1 targeting to Golgi membranes in cells. Our data imply that HDS1 and PH domains are functionally analogous in that each uses lipid-based membrane information to regulate GEF recruitment. Lipid-based recruitment of GBF1 extends the paradigm of lipid regulation to small and large GEFs and suggests that lipid-based mechanisms evolved early during GEF diversification.

This article has an associated First Person interview with the first author of the paper.
Abscisic acid – an anti-angiogenic phytohormone that modulates the phenotypical plasticity of endothelial cells and macrophages
Authors: Chaqour Julienne , Lee Sangmi , Ravichandra Aashreya , Chaqour Brahim
Published: February 2018

Abscisic acid (ABA) has shown anti-inflammatory and immunoregulatory properties in preclinical models of diabetes and inflammation. Herein, we studied the effects of ABA on angiogenesis, a strictly controlled process that, when dysregulated, leads to severe angiogenic disorders including vascular overgrowth, exudation, cellular inflammation and organ dysfunction. By using a 3D sprouting assay, we show that ABA effectively inhibits migration, growth and expansion of endothelial tubes without affecting cell viability. Analyses of the retinal vasculature in developing normoxic and hyperoxic mice challenged by oxygen toxicity reveal that exogenously administered ABA stunts the development and regeneration of blood vessels. In these models, ABA downregulates endothelial cell (EC)-specific growth and migratory genes, interferes with tip and stalk cell specification, and hinders the function of filopodial protrusions required for precise guidance of vascular sprouts. In addition, ABA skews macrophage polarization towards the M1 phenotype characterized by anti-angiogenic marker expression. In accordance with this, ABA treatment accelerates macrophage-induced programmed regression of fetal blood vessels. These findings reveal protective functions of ABA against neovascular growth through modulation of EC and macrophage plasticity, suggesting the potential utility of ABA as a treatment in vasoproliferative diseases.
Recent insights into the cellular and molecular determinants of aging
Authors: Ruan Linhao , Zhang Xi , Li Rong
Published: February 2018

Aging is the gradual decline of physiological functions and organismal fitness, which leads to age-dependent fitness loss, diseases and eventually mortality. Understanding the cause of aging constitutes one of most intriguing areas of research in biology. On both the cellular and molecular levels, it has been hypothesized that there are aging determinants to control the onset and progression of aging, including the loss of beneficial components and accumulation of detrimental factors. This Review highlights the recent advance in identifying various factors that affect the aging process, focusing on how these determinants affect the lifespan and fitness of a cell or organism. With more and more aging determinants revealed, further understanding about their functions and interconnections could enable the development of specific intervention to extend healthy lifespan and reduce the risk of age-related diseases.
The importance of membrane microdomains for bile salt-dependent biliary lipid secretion
Authors: Eckstein Johannes , Holzhütter Hermann-Georg , Berndt Nikolaus
Published: February 2018

Alternative models explaining the biliary lipid secretion at the canalicular membrane of hepatocytes exist: successive lipid extraction by preformed bile salt micelles, or budding of membrane fragments with formation of mixed micelles. To test the feasibility of the latter mechanism, we developed a mathematical model that describes the formation of lipid microdomains in the canalicular membrane. Bile salt monomers intercalate into the external hemileaflet of the canalicular membrane, to form a rim to liquid disordered domain patches that then pinch off to form nanometer-scale mixed micelles. Model simulations perfectly recapitulate the measured dependence of bile salt-dependent biliary lipid extraction rates upon modulation of the membrane cholesterol (lack or overexpression of the cholesterol transporter Abcg5–Abcg8) and phosphatidylcholine (lack of Mdr2, also known as Abcb4) content. The model reveals a strong dependence of the biliary secretion rate on the protein density of the membrane. Taken together, the proposed model is consistent with crucial experimental findings in the field and provides a consistent explanation of the central molecular processes involved in bile formation.