bluuebunny/crossref_metadata_2025 huggingface dataset:
Threats to Oaks in the Eastern United States: Perceptions and Expectations of Experts
Authors: Conrad Anna O , Crocker Ellen V , Li Xiaoshu , Thomas William R , Ochuodho Thomas O , Holmes Thomas P , Nelson C Dana
Published: November 2019

Oaks (Quercus spp.) are keystone species in many ecosystems and are ecologically as well as economically valuable. The objective of this study was to gather and evaluate information from a diverse group of oak experts on current and future biotic and abiotic threats to oaks in the eastern United States. Using a Delphi survey method with three iterative surveys, we found that oak decline and climate change were identified as critical current and future threats, respectively, in this region. Focusing on climate change, experts were asked a series of questions to assess its potential future temporal and spatial impact on oaks. With respect to climate change, the majority of experts surveyed believe climate change will manifest gradually, although they were generally uncertain about the geographical distribution of climate change in the future, i.e., the areas where oaks are likely to be impacted by climate change in the future. New/emerging pests and pathogens were seen as the most critical future threat by the third survey round. Results from this study can be used to better inform management practices and research priorities for ensuring resilient oak resources for the future.
Beyond the darkness: recent lessons from etiolation and de-etiolation studies
Authors: Armarego-Marriott Tegan , Sandoval-Ibañez Omar , Kowalewska Łucja
Published: November 2019

The state of etiolation is generally defined by the presence of non-green plastids (etioplasts) in plant tissues that would normally contain chloroplasts. In the commonly used dark-grown seedling system, etiolation is coupled with a type of growth called skotomorphogenesis. Upon illumination, de-etiolation occurs, marked by the transition from etioplast to chloroplast, and, at the seedling level, a switch to photomorphogenic growth. Etiolation and de-etiolation systems are therefore important for understanding both the acquisition of photosynthetic capacity during chloroplast biogenesis and plant responses to light—the most relevant signal in the life and growth of the organism. In this review, we discuss recent discoveries (within the past 2–3 years) in the field of etiolation and de-etiolation, with a particular focus on post-transcriptional processes and ultrastructural changes. We further discuss ambiguities in definitions of the term ‘etiolation’, and benefits and biases of common etiolation/de-etiolation systems. Finally, we raise several open questions and future research possibilities.
The Silver Lining: Advances in the Surgical Management of Brain Trauma Attributable to War
Authors: Janatpour Zachary C , Welch Matthew C , Shanmuga Santosh , Curry Brian P , Coughlin Daniel J , Sabersky Abraham E , Bell Randy S , Gilhooly Jonathan E
Published: November 2019

Within the text we elaborate on the relationship between war and medicine, particularly as it pertains to neurosurgery and the management of brain trauma, and emphasize neurosurgical advancements in the treatment of brain trauma gleaned from U.S.-involved conflicts of the 21st century.
Orthopedic Surgeon Decision-Making Processes for Postsurgical Opioid Prescribing
Authors: Kopp Jason A , Anderson Ashley B , Dickens Jonathan F , Graf Andrew C , Reid Crevan O , Cagniart Pierre-Etienne C , Wang Jason M , Highland Krista B
Published: November 2019

Introduction

Acute pain and chronic pain are significant burdens in the Department of Defense, compounded by the ongoing opioid crisis. Given the ubiquity of (leftover) opioid prescriptions following orthopedic surgery, it is essential to identify feasible and acceptable avenues of opioid risk mitigation efforts. The present quality improvement project builds on recent studies by evaluating factors related to opioid prescribing decisions in a sample of orthopedic surgery providers.

Materials and Methods

This quality improvement project received a Determination of Not Research and was conducted through a collaboration between the Department of Orthopaedic Surgery and the Department of Anesthesiology and Pain Management at Walter Reed National Military Medical Center. Providers in the Department of Orthopaedic Surgery completed an anonymous online survey assessing opioid prescribing education, factors influencing prescribing practices, opioid-safety practices, and perspectives on potential opioid safety initiatives.

Results

In total, 39 respondents completed surveys. There was variability in exposure to different types of opioid prescribing education, with some variation between attendings/physician assistants and residents. Patients’ acute postsurgical pain, using a standardized amount for most patients, and prescription histories were the three most influential factors. Concern of patients running out and fear of patient dissatisfaction were the least influential factors. Respondents commonly reported engagement in promoting nonpharmacological pain management, as well as coordinating with chronic pain providers when applicable, but did not commonly report educating patients on leftover opioid disposal. Respondents indicated that a barrier to opioid risk mitigation was the difficulty of accessing appropriate electronic health record data to inform decisions. Lastly, they reported openness to proposed opioid safety initiatives.

Conclusion

The results of this quality improvement project identified several target areas for future initiatives focused on improving opioid prescribing practices. This included a provider training program, improved patient education system, increased awareness and use of opioid tracking databases, and development of a standardized (but adaptable per patient characteristics and history) recommended dose for common orthopedic surgeries. Future projects will target tailored development, implementation, and evaluation of such efforts.
Understanding as a Source of Justification
Authors: Horvath Joachim
Published: November 2019

The traditional epistemological approach towards judgments like BACHELORS ARE UNMARRIED or ALL KNOWLEDGE IS TRUE is that they are justified or known on the basis of understanding alone. In this paper, I develop an understanding-based account which takes understanding to be a sufficient source of epistemic justification for the relevant judgments. Understanding-based accounts face the problem of the rational revisability of almost all human judgments. Williamson has recently developed a reinforced version of this problem: the challenge from expert revisability. This is the problem that even the best candidate judgments for understanding-based justification can be rationally rejected by the relevant experts, who may not even have any disposition or inclination to accept these judgments. (Consider, for instance, Graham Priest, a leading logician who rejects the law of non-contradiction.) However, I argue that expert revisability is fully compatible with the proposed understanding-based epistemology, because expert revisability is true of sufficient sources of epistemic justification in general. A remaining metaphysical worry is that understanding might end up being ‘too thin’ to play the envisaged epistemological role. This worry can be countered with a novel metaphysics of understanding involving second-order dispositions.
Idealism and the Identity Theory of Truth
Authors: Trueman Robert
Published: November 2019

In a recent article, Hofweber (2019) presents a new, and surprising, argument for idealism. His argument is surprising because it starts with an apparently innocent premiss from the philosophy of language: that ‘that’-clauses do not refer. I do not think that Hofweber's argument works, and my first aim in this paper is to explain why. However, I agree with Hofweber that what we say about ‘that’-clauses has important metaphysical consequences. My second aim is to argue that, far from leading us into idealism, denying that ‘that’-clauses refer is the first step toward a kind of direct realism about belief.
‘Master of the Orchester with a Sallary’: Handel at the Bank of England
Authors: Harris Ellen T
Published: November 2019

The discovery of an account held by Handel at the Bank of England in 1721 offers new documentary information about his financial transactions and evidence for his residence before the move to Brook Street. Careful consideration of the circumstances surrounding this account leads to a reinterpretation of Handel’s short-lived accounts with the Royal African Company in 1720 and sheds light on Handel’s South Sea Annuities account (1723–32). An analysis of the South Sea Annuities account clarifies its origin and explains its pattern of credits and withdrawals, suggests the exact salary Handel received from the Royal Academy of Music as ‘Master of the Orchester’, and indicates that the financial arrangements for Handel’s salary that had been in place from the inception of the Academy were continued at the beginning of the ‘Second Academy’.
Compact groups from semi-analytical models of galaxy formation – I. A comparative study of frequency and nature
Authors: Díaz-Giménez E , Taverna A , Zandivarez A , Mamon G A
Published: November 2019

Compact groups (CGs) of galaxies are defined as isolated and dense galaxy systems that appear to be a unique site of multiple galaxy interactions. Semi-analytical models (SAMs) of galaxy formation are a prime tool to understand CGs. We investigate how the frequency and the 3D nature of CGs depends on the SAM and its underlying cosmological parameters. Extracting nine light-cones of galaxies from five different SAMs and selecting CGs as in observed samples, we find that the frequency and nature of CGs depends strongly on the cosmological parameters. Moving from the WMAP1 to the WMAP7 and Planck cosmologies (increasing density of the Universe and decreasing normalization of the power spectrum), the space density of CGs is decreased by a factor 2.5, while the fraction of CGs that are physically dense falls from 50 to 35 per cent. The lower σ8 leads to fewer dense groups, while the higher Ωm causes more chance alignments. However, with increased mass and spatial resolution, the fraction of CGs that are physically dense is pushed back up to 50 per cent. The intrinsic differences in the SAM recipes also lead to differences in the frequency and nature of CGs, particularly those related to how SAMs treat orphan galaxies. We find no dependence of CG properties on the flux limit of the mock catalogues nor on the waveband in which galaxies are selected. One should thus be cautious when interpreting a particular SAM for the frequency and nature of CGs.
Are inner disc misalignments common? ALMA reveals an isotropic outer disc inclination distribution for young dipper stars
Authors: Ansdell M , Gaidos E , Hedges C , Tazzari M , Kraus A L , Wyatt M C , Kennedy G M , Williams J P , Mann A W , Angelo I , Dûchene G , Mamajek E E , Carpenter J , Esplin T L , Rizzuto A C
Published: November 2019

Dippers are a common class of young variable star exhibiting day-long dimmings with depths of up to several tens of per cent. A standard explanation is that dippers host nearly edge-on (id ≈ 70°) protoplanetary discs that allow close-in (<1 au) dust lifted slightly out of the mid-plane to partially occult the star. The identification of a face-on dipper disc and growing evidence of inner disc misalignments brings this scenario into question. Thus, we uniformly (re)derive the inclinations of 24 dipper discs resolved with (sub-)mm interferometry from ALMA. We find that dipper disc inclinations are consistent with an isotropic distribution over id ≈ 0−75°, above which the occurrence rate declines (likely an observational selection effect due to optically thick disc mid-planes blocking their host stars). These findings indicate that the dipper phenomenon is unrelated to the outer (>10 au) disc resolved by ALMA and that inner disc misalignments may be common during the protoplanetary phase. More than one mechanism may contribute to the dipper phenomenon, including accretion-driven warps and ‘broken’ discs caused by inclined (sub-)stellar or planetary companions.
Photometric rotation periods for 107 M dwarfs from the APACHE survey
Authors: Giacobbe P , Benedetto M , Damasso M , Sozzetti A , Christille J M , Lattanzi M G , Calcidese P , Carbognani A , Barbato D , Pinamonti M , Poggio E , Lanza A F , Bernagozzi A , Cenadelli D , Lanteri L , Bertolini E
Published: November 2019

We present rotation period measurements for 107 M dwarfs in the mass range $0.15\!-\!0.70 \, \mathrm{M}_\odot$ observed within the context of the APACHE photometric survey. We measure rotation periods in the range 0.5–190 d, with the distribution peaking at ∼30 d. We revise the stellar masses and radii for our sample of rotators by exploiting the Gaia DR2 data. For ${\sim}20{{\ \rm per\ cent}}$ of the sample, we compare the photometric rotation periods with those derived from different spectroscopic indicators, finding good correspondence in most cases. We compare our rotation periods distribution to the one obtained by the Kepler survey in the same mass range, and to that derived by the MEarth survey for stars in the mass range $0.07\!-\!0.25 \, \mathrm{M}_\odot$. The APACHE and Kepler periods distributions are in good agreement, confirming the reliability of our results, while the APACHE distribution is consistent with the MEarth result only for the older/slow rotators, and in the overlapping mass range of the two surveys. Combining the APACHE/Kepler distribution with the MEarth distribution, we highlight that the rotation period increases with decreasing stellar mass, in agreement with previous work. Our findings also suggest that the spin-down time scale, from fast to slow rotators, changes crossing the fully convective limit at ${\approx}0.3 \, \mathrm{M}_\odot$ for M dwarfs. The catalogue of 107 rotating M dwarfs presented here is particularly timely, as the stars are prime targets for the potential identification of transiting small planets with TESS and amenable to high-precision mass determination and further atmospheric characterization measurements.
When a Music Therapist Grieves
Authors: Sato Yumiko
Published: November 2019

When my brother died suddenly at the age of 34, I had been working as a hospice music therapist for over 6 years. Understanding the grief process intellectually was quite different from experiencing it. I felt overwhelmed by facing the loss and grief of others at work, while I was still in shock about my brother’s death. Over time, the grieving process took so much out of me that I did not feel I had enough emotional energy to work with people who were dying and their loved ones. I began to have doubts: Can I be an effective therapist for my clients when I’m struggling with my own grief? Is it ethical for me to practice as a hospice music therapist right now? A year after my brother’s death I met a patient who was suffering from the trauma of war. Witnessing her recovery changed the way I thought about my grief and my role as a therapist. In the end, it was the work itself that helped me understand and work through my grief.
Effector gene silencing mediated by histone methylation underpins host adaptation in an oomycete plant pathogen
Authors: Wang Liyuan , Chen Han , Li JiangJiang , Shu Haidong , Zhang Xiangxue , Wang Yuanchao , Tyler Brett M , Dong Suomeng
Published: November 2019

The relentless adaptability of pathogen populations is a major obstacle to effective disease control measures. Increasing evidence suggests that gene transcriptional polymorphisms are a strategy deployed by pathogens to evade host immunity. However, the underlying mechanisms of transcriptional plasticity remain largely elusive. Here we found that the soybean root rot pathogen Phytophthora sojae evades the soybean Resistance gene Rps1b through transcriptional polymorphisms in the effector gene Avr1b that occur in the absence of any sequence variation. Elevated levels of histone H3 Lysine27 tri-methylation (H3K27me3) were observed at the Avr1b locus in a naturally occurring Avr1b-silenced strain but not in an Avr1b-expressing strain, suggesting a correlation between this epigenetic modification and silencing of Avr1b. To genetically test this hypothesis, we edited the gene, PsSu(z)12, encoding a core subunit of the H3K27me3 methyltransferase complex by using CRISPR/Cas9, and obtained three deletion mutants. H3K27me3 depletion within the Avr1b genomic region correlated with impaired Avr1b gene silencing in these mutants. Importantly, these mutants lost the ability to evade immune recognition by soybeans carrying Rps1b. These data support a model in which pathogen effector transcriptional polymorphisms are associated with changes in chromatin epigenetic marks, highlighting epigenetic variation as a mechanism of pathogen adaptive plasticity.
Dihydropyrimidinase protects from DNA replication stress caused by cytotoxic metabolites
Authors: Basbous Jihane , Aze Antoine , Chaloin Laurent , Lebdy Rana , Hodroj Dana , Ribeyre Cyril , Larroque Marion , Shepard Caitlin , Kim Baek , Pruvost Alain , Moreaux Jérôme , Maiorano Domenico , Mechali Marcel , Constantinou Angelos
Published: November 2019

Imbalance in the level of the pyrimidine degradation products dihydrouracil and dihydrothymine is associated with cellular transformation and cancer progression. Dihydropyrimidines are degraded by dihydropyrimidinase (DHP), a zinc metalloenzyme that is upregulated in solid tumors but not in the corresponding normal tissues. How dihydropyrimidine metabolites affect cellular phenotypes remains elusive. Here we show that the accumulation of dihydropyrimidines induces the formation of DNA–protein crosslinks (DPCs) and causes DNA replication and transcriptional stress. We used Xenopus egg extracts to recapitulate DNA replication invitro. We found that dihydropyrimidines interfere directly with the replication of both plasmid and chromosomal DNA. Furthermore, we show that the plant flavonoid dihydromyricetin inhibits human DHP activity. Cellular exposure to dihydromyricetin triggered DPCs-dependent DNA replication stress in cancer cells. This study defines dihydropyrimidines as potentially cytotoxic metabolites that may offer an opportunity for therapeutic-targeting of DHP activity in solid tumors.
Presentations for Subrings and Subalgebras of Finite CO-Rank
Authors: Mayr Peter , Ruškuc Nik
Published: November 2019

Let $K$ be a commutative Noetherian ring with identity, let $A$ be a $K$-algebra and let $B$ be a subalgebra of $A$ such that $A/B$ is finitely generated as a $K$-module. The main result of the paper is that $A$ is finitely presented (resp. finitely generated) if and only if $B$ is finitely presented (resp. finitely generated). As corollaries, we obtain: a subring of finite index in a finitely presented ring is finitely presented; a subalgebra of finite co-dimension in a finitely presented algebra over a field is finitely presented (already shown by Voden in 2009). We also discuss the role of the Noetherian assumption on $K$ and show that for finite generation it can be replaced by a weaker condition that the module $A/B$ be finitely presented. Finally, we demonstrate that the results do not readily extend to non-associative algebras, by exhibiting an ideal of co-dimension $1$ of the free Lie algebra of rank 2 which is not finitely generated as a Lie algebra.
Long term follow-up of Behçet’s syndrome patients treated with cyclophosphamide
Authors: Gurcan Mert , Esatoglu Sinem Nihal , Hamuryudan Vedat , Saygin Didem , Ugurlu Serdal , Seyahi Emire , Melikoglu Melike , Fresko Izzet , Yurdakul Sebahattin , Yazici Hasan , Hatemi Gulen
Published: November 2019

Objectives

CYC remains an important treatment option for Behçet’s syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients.

Methods

We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome.

Results

Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15–26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients.

Conclusion

Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC.
Complications of therapy for ANCA-associated vasculitis
Authors: Smith Rona
Published: November 2019

The introduction of immunosuppressive therapies has transformed ANCA-associated vasculitis (AAV) from a largely fatal condition to a chronic relapsing disorder. However, progressive organ damage and disability, both from the disease process itself and from therapies used for treatment, eventually affect the majority of patients. Infection, rather than uncontrolled vasculitis, is the greatest cause of early mortality and remains a major problem thereafter. Increased rates of malignancy and cardiovascular disease are additional important long term sequelae. This review focuses on the complications associated with the immunosuppressive therapies most commonly used to treat ANCA-associated vasculitis, and considers prophylactic and monitoring strategies to minimize these risks. Achieving a balance between immunosuppression to reduce relapse risk and minimizing the adverse effects associated with therapy has become key. The contribution of glucocorticoids to treatment toxicity is increasingly being recognized, and future therapeutic strategies must concentrate on glucocorticoid minimization or sparing strategies. Development of robust predictors of an individual’s future clinical course is needed in order to individually tailor treatment regimens.
Quantitative analysis of the placebo response in pharmacotherapy of insomnia and its application in clinical trials
Authors: Zheng Xijun , He Yingchun , Xu Ling , Li Yunfei , Yin Fang , Li Huafang , Liu Hongxia , Shen Yifeng , Zheng Qingshan , Li Lujin
Published: November 2019

Study Objectives

This study aimed to develop a robust placebo response model for the pharmacotherapy for insomnia to guide drug development and clinical practice.

Methods

PubMed, EMBASE, and Cochrane Library databases were systematically searched for randomized placebo-controlled trials of medications for insomnia dating from the inception dates of the databases to April 18, 2018. Three placebo response models were established to describe the time–course of sleep parameters measured by objective (polysomnography or actigraphy) or subjective methods (sleep diary or questionnaires). The established models were applied to simulate placebo response distribution under different conditions using Monte Carlo simulations.

Results

Fifty-four studies involving 6,416 subjects were included. Placebo response increased over time and reached a plateau at approximately 8 weeks from start of therapy. Established models described the observed data reasonably well based on various diagnostic plots. Baseline sleep parameters affected the placebo response. There were significant positive correlations with placebo response and the severity of sleep latency, wake after sleep onset, and total sleep time at baseline. In addition, placebo response, assessed by subjective and objective methods, was consistent after correcting the baseline levels.

Conclusions

The established placebo response models can serve as a tool to predict placebo response at different baseline levels, which can provide valuable reference for clinical trial design, decision-making in drug development, and clinical practice.
Sleepiness as motivation: a potential mechanism for how sleep deprivation affects behavior
Authors: Axelsson John , Ingre Michael , Kecklund Göran , Lekander Mats , Wright Kenneth P , Sundelin Tina
Published: November 2019

Study Objectives

To determine how sleepiness and sleep deprivation drive the motivation to engage in different behaviors.

Methods

We studied the sleepiness of 123 participants who had been randomized to sleep deprivation or normal sleep, and their willingness to engage in a range of everyday behaviors.

Results

Self-reported sleepiness was a strong predictor of the motivation to engage in sleep-preparatory behaviors such as shutting one’s eyes (OR = 2.78, 95% CI: 2.19–3.52 for each step up on the Karolinska Sleepiness Scale) and resting (OR = 3.20, CI: 2.46–4.16). Sleepiness was also related to the desire to be cared for by a loved one (OR = 1.49, CI: 1.22–1.82), and preparedness to utilize monetary and energy resources to get to sleep. Conversely, increased sleepiness was associated with a decreased motivation for social and physical activities (e.g. be with friends OR = 0.71, CI: 0.61–0.82; exercise OR = 0.65, CI: 0.56–0.76). Sleep deprivation had similar effects as sleepiness on these behaviors. Neither sleepiness nor sleep deprivation had strong associations with hunger, thirst, or food preferences.

Conclusions

Our findings indicate that sleepiness is a dynamic motivational drive that promotes sleep-preparatory behaviors and competes with other drives and desired outcomes. Consequently, sleepiness may be a central mechanism by which impaired alertness, for example, due to insufficient sleep, contributes to poor quality of life and adverse health. We propose that sleepiness helps organize behaviors toward the specific goal of assuring sufficient sleep, in competition with other needs and incentives. A theoretical framework on sleepiness and its behavioral consequences are likely to improve our understanding of several disease mechanisms.
Protease activated receptors (PAR)‐1 and ‐2 mediate cellular effects of factor VII activating protease (FSAP)
Authors: Byskov Kristina , Le Gall Sylvain M. , Thiede Bernd , Camerer Eric , Kanse Sandip M.
Published: November 2019

Factor VII activating protease (FSAP) is a circulating serine protease implicated in thrombosis, atherosclerosis, stroke, and cancer. Using an overexpression strategy, we have systematically investigated the role of protease activated receptors (PAR)‐1, ‐2, ‐3, and ‐4 on FSAP‐mediated signaling in HEK293T and A549 cells. Cleavage of PAR‐reporter constructs and MAPK phosphorylation was used to monitor receptor activation. FSAP cleaved PAR‐2 and to a lesser degree PAR‐1, but not PAR‐3 or PAR‐4 in both cell types. Robust MAPK activation in response to FSAP was observed after PAR‐2, but not PAR‐1 overexpression in HEK293T. Recombinant serine protease domain of wild type FSAP, but not the Marburg I isoform of FSAP, could reproduce the effects of plasma purified FSAP. Canonical cleavage of both PARs was suggested by mass spectrometric analysis of synthetic peptide substrates from the N‐terminus of PARs and site directed mutagenesis studies. Surprisingly, knockdown of endogenous PAR‐1, but not PAR‐2, prevented the apoptosis‐inhibitory effect of FSAP, suggesting that PAR1 is nevertheless a direct or indirect target in some cell types. This molecular characterization of PAR‐1 and ‐2 as cellular receptors of FSAP will help to define the actions of FSAP in the context of cancer and vascular biology.
Ischemia‐induced Netrin‐4 promotes neovascularization through endothelial progenitor cell activation via Unc‐5 Netrin receptor B
Authors: Lee Na Geum , Jeung In Cheul , Heo Soon Chul , Song Jinhoi , Kim Wooil , Hwang Byungtae , Kwon Min‐Gi , Kim Yeon‐Gu , Lee Jangwook , Park Jong‐Gil , Shin Min‐Gyeong , Cho Young‐Lai , Son Mi‐Young , Bae Kwang‐Hee , Lee Sang‐Hyun , Kim Jae Ho , Min Jeong‐Ki
Published: November 2019

Endothelial progenitor cells (EPCs) promote neovascularization and tissue repair by migrating to vascular injury sites; therefore, factors that enhance EPC homing to damaged tissues are of interest. Here, we provide evidence of the prominent role of the Netrin‐4 (NTN4)–Unc‐5 Netrin receptor B (UNC5B) axis in EPC‐specific promotion of ischemic neovascularization. Our results showed that NTN4 promoted the proliferation, chemotactic migration, and paracrine effects of small EPCs (SEPCs) and significantly increased the incorporation of large EPCs (LEPCs) into tubule networks. Additionally, NTN4 prominently augmented neovascularization in mice with hindlimb ischemia by increasing the homing of exogenously transplanted EPCs to the ischemic limb and incorporating EPCs into vessels. Moreover, silencing of UNC5B, an NTN4 receptor, abrogated the NTN4‐induced cellular activities of SEPCs in vitro and blood‐flow recovery and neovascularization in vivo in ischemic muscle by reducing EPC homing and incorporation. These findings suggest NTN4 as an EPC‐based therapy for treating angiogenesis‐dependent diseases.
A novel F‐box domain containing cyclin F like gene is required for maintaining the genome stability and survival of chicken primordial germ cells
Authors: Lee Bo Ram , Rengaraj Deivendran , Choi Hee Jung , Han Jae Yong
Published: November 2019

The stability and survival of germ cells are controlled by the germline‐specific genes, however, such genes are less known in the avian species. Using a microarray‐based the National Center for Biotechnology Information Gene Expression Omnibus dataset, we found an unigene (Gga.9721) that upregulated in the chicken primordial germ cells (PGCs). The unigene showed 97% identities with an uncharacterized chicken cyclin F like gene. The predicted chicken cyclin F like gene was further characterized through expression and regulation in the chicken PGCs. The sequence analysis revealed that the gene shows identities with cyclin F gene and contains an F‐box domain. The expression of chicken cyclin F like was detected specifically in the gonads, PGCs, and germline cells. The knockdown of cyclin F like gene resulted in DNA damage and apoptosis in the PGCs. The genes related to stemness and germness were downregulated, whereas, genes related to apoptosis and DNA damage response were increased in the PGCs after the knockdown of chicken cyclin F like. We further observed that the Nanog homeobox controlled the transcriptional activity of chicken cyclin F like gene in PGCs. Collectively, the chicken cyclin F like gene, which is not reported in any other species, is required for maintaining the genome stability of germ cells.
Glucosylceramide synthase regulates adipo‐osteogenic differentiation through synergistic activation of PPARγ with GlcCer
Authors: Jang Hyun‐Jun , Lim Seyoung , Kim Jung‐Min , Yoon Sora , Lee Chae Young , Hwang Hyeon‐Jeong , Shin Jeong Woo , Shin Kyeong Jin , Kim Hye Yun , Park Kwang Il , Nam Dougu , Lee Ja Yil , Yea Kyungmoo , Hirabayashi Yoshio , Lee Yu Jin , Chae Young Chan , Suh Pann‐Ghill , Choi Jang Hyun
Published: November 2019

Dysregulation of the adipo‐osteogenic differentiation balance of mesenchymal stem cells (MSCs), which are common progenitor cells of adipocytes and osteoblasts, has been associated with many pathophysiologic diseases, such as obesity, osteopenia, and osteoporosis. Growing evidence suggests that lipid metabolism is crucial for maintaining stem cell homeostasis and cell differentiation; however, the detailed underlying mechanisms are largely unknown. Here, we demonstrate that glucosylceramide (GlcCer) and its synthase, glucosylceramide synthase (GCS), are key determinants of MSC differentiation into adipocytes or osteoblasts. GCS expression was increased during adipogenesis and decreased during osteogenesis. Targeting GCS using RNA interference or a chemical inhibitor enhanced osteogenesis and inhibited adipogenesis by controlling the transcriptional activity of peroxisome proliferator‐activated receptor γ (PPARγ). Treatment with GlcCer sufficiently rescued adipogenesis and inhibited osteogenesis in GCS knockdown MSCs. Mechanistically, GlcCer interacted directly with PPARγ through A/B domain and synergistically enhanced rosiglitazone‐induced PPARγ activation without changing PPARγ expression, thereby treatment with exogenous GlcCer increased adipogenesis and inhibited osteogenesis. Animal studies demonstrated that inhibiting GCS reduced adipocyte formation in white adipose tissues under normal chow diet and high‐fat diet feeding and accelerated bone repair in a calvarial defect model. Taken together, our findings identify a novel lipid metabolic regulator for the control of MSC differentiation and may have important therapeutic implications.
Lack of PDZD7 long isoform disrupts ankle‐link complex and causes hearing loss in mice
Authors: Du Haibo , Zou Linzhi , Ren Rui , Li Nana , Li Jie , Wang Yanfei , Sun Jinpeng , Yang Jun , Xiong Wei , Xu Zhigang
Published: November 2019

Usher syndrome (USH) is the most frequent form of combined hereditary deafness‐blindness, characterized by hearing loss and retinitis pigmentosa, with or without vestibular dysfunction. PDZD7 is a PDZ domain‐containing scaffold protein that was suggested to be a USH modifier and a contributor to digenic USH. In the inner ear hair cells, PDZD7 localizes at the ankle region of the stereocilia and constitutes the so‐called ankle‐link complex together with three other USH proteins Usherin, WHRN, and ADGRV1. PDZD7 gene is subjected to alternative splicing, which gives rise to two types of PDZD7 isoforms, namely the long and short isoforms. At present, little is known which specific isoform is involved in ankle‐link formation and stereocilia development. In this work, we showed that PDZD7 long isoform, but not short isoforms, localizes at the ankle region of the stereocilia. Moreover, we established Pdzd7 mutant mice by introducing deletions into exon 14 of the Pdzd7 gene, which causes potential premature translational stop in the long isoform but leaves short isoforms unaffected. We found that lack of PDZD7 long isoform affects the localization of other ankle‐link complex components in the stereocilia. Consequently, Pdzd7 mutant mice showed stereocilia development deficits and hearing loss as well as reduced mechanotransduction (MET) currents, suggesting that PDZD7 long isoform is indispensable for hair cells. Furthermore, by performing yeast two‐hybrid screening, we identified a PDZD7 long isoform‐specific binding partner PIP5K1C, which has been shown to play important roles in hearing and might participate in the function and/or transportation of PDZD7.
Therapies targeting Frizzled‐7/β‐catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model
Authors: Bats Marie‐Lise , Bougaran Pauline , Peghaire Claire , Gueniot Florian , Abelanet Alice , Chan Hélène , Séguy Camille , Jeanningros Sylvie , Jaspard‐Vinassa Béatrice , Couffinhal Thierry , Duplàa Cécile , Dufourcq Pascale
Published: November 2019

Retinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction of anti‐angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies. However, limitations associated with anti‐VEGF medications require to unravel new pathways of vessel growth to identify potential drug targets. Here, we investigated the role of Wnt/Frizzled‐7 (Fzd7) pathway in a mouse model of oxygen‐induced retinopathy (OIR). Using transgenic mice, which enabled endothelium‐specific and time‐specific Fzd7 deletion, we demonstrated that Fzd7 controls both vaso‐obliteration and neovascular phases (NV). Deletion of Fzd7 at P12, after the ischemic phase of OIR, prevented formation of aberrant neovessels into the vitreous by suppressing proliferation of endothelial cells (EC) in tufts. Next we validated in vitro two Frd7 blocking strategies: a monoclonal antibody (mAbFzd7) against Fzd7 and a soluble Fzd7 receptor (CRD). In vivo a single intravitreal microinjection of mAbFzd7 or CRD significantly attenuated retinal neovascularization (NV) in mice with OIR. Molecular analysis revealed that Fzd7 may act through the activation of Wnt/β‐catenin and Jagged1 expression to control EC proliferation in extra‐retinal neovessels. We identified Fzd7/β‐catenin signaling as new regulator of pathological retinal NV. Fzd7 appears to be a potent pharmacological target to prevent or treat aberrant angiogenesis of ischemic retinopathies.
Grb2 binding induces phosphorylation-independent activation of Shp2
Authors: Lin Chi-Chuan , Wieteska Lukasz , Suen Kin Man , Kalverda Arnout , Ahmed Zamal , Ladbury John E.
Published: November 2019

The regulation of phosphatase activity is fundamental to the control of intracellular signalling and in particular the tyrosine kinase-mediated mitogen-activated protein kinase (MAPK) pathway. Shp2 is a ubiquitously expressed protein tyrosine phosphatase and its kinase-induced hyperactivity is associated with many cancer types. In non-stimulated cells we find that binding of the adaptor protein, Grb2, in its monomeric state initiates Shp2 activity independent of phosphatase phosphorylation. Grb2 forms a bidentate interaction with both the N-terminal SH2 and the catalytic domains of Shp2, releasing the phosphatase from its auto-inhibited conformation. Grb2 typically exists as a dimer in the cytoplasm. However, its monomeric state prevails under basal conditions when it is expressed at low concentration, or when it is constitutively phosphorylated on a specific tyrosine residue (Y160). Thus, Grb2 can activate Shp2 and downstream signal transduction, in the absence of extracellular growth factor stimulation or kinase-activating mutations, in response to defined cellular conditions. We identify a polypeptide biotool capable of blocking the Grb2-Shp2 interaction. This peptide down-regulates Shp2 activityin vitroand MAPK signalling in a cancer cell line.
Cell Tracking Profiler: a user-driven analysis framework for evaluating 4D live cell imaging data
Authors: Mitchell Claire , Caroff Lauryanne , Vigilante Alessandra , Solis-Lemus Jose Alonso , Reyes-Aldasoro Constantino Carlos , de Chaumont Fabrice , Dufour Alexandre , Dallongeville Stephane , Olivo-Marin Jean-Christophe , Knight Robert
Published: November 2019

Accurate measurements of cell morphology and behaviour are fundamentally important for understanding how disease, molecules and drugs affect cell function in vivo. Using muscle stem cell (muSC) responses to injury in zebrafish as our biological paradigm we have established a ground truth for muSC cell behaviour. This revealed that variability in segmentation and tracking algorithms from commonly used programs are error-prone, leading us to develop a fast semi-automated image analysis pipeline that allows user defined parameters for segmentation and correction of cell tracking. Cell Tracking Profiler (CTP) operates through the freely available Icy platform, and allows user-managed cell tracking from 3D time-lapsed datasets to provide measures of cell shape and movement. Using dimensionality reduction methods, multiple correlation and regression analyses we identify myosin II-dependent parameters of muSC behaviour during regeneration. CTP and the associated statistical tools we have developed thus provide a powerful framework for analysing complex cell behaviour in vivo from 4D datasets.

Analysis of cell shape and movement from 3D time-lapsed datasets is currently very challenging. We therefore designed Cell Tracking Profiler for analysing cell behaviour from complex datasets and demonstrate its effectiveness by analysing stem cell behaviour during muscle regeneration in zebrafish.
Optimizing assembly sequence planning using precedence graph-based assembly subsets prediction method
Authors: Zhang Nan , Liu Zhenyu , Qiu Chan , Hu Weifei , Tan Jianrong
Published: November 2019

Purpose

Assembly sequence planning (ASP) plays a vital role in assembly process because it directly influences the feasibility, cost and time of the assembly process. The purpose of this study is to solve ASP problem more efficiently than current algorithms.

Design/methodology/approach

A novel assembly subsets prediction method based on precedence graph is proposed to solve the ASP problem. The proposed method adopts the idea of local to whole and integrates a simplified firework algorithm. First, assembly subsets are generated as initial fireworks. Then, each firework explodes to several sparks with higher-level assembly subsets and new fireworks are selected for next generation according to selection strategy. Finally, iterating the algorithm until complete and feasible solutions are generated.

Findings

The proposed method performs better in comparison with state-of-the-art algorithms because of the balance of exploration (fireworks) and exploitation (sparks). The size of initial fireworks population determines the diversity of the solution, so assembly subsets prediction method based on precedence graph (ASPM-PG) can explore the solution space. The size of sparks controls the exploitation ability of ASPM-PG; with more sparks, the direction of a specific firework can be adequately exploited.

Practical implications

The proposed method is with simple structure and high efficiency. It is anticipated that using the proposed method can effectively improve the efficiency of ASP and reduce computing cost for industrial applications.

Originality/value

The proposed method finds the optimal sequence in the construction process of assembly sequence rather than adjusting order of a complete assembly sequence in traditional methods. Moreover, a simplified firework algorithm with new operators is introduced. Two basic size parameters are also analyzed to explain the proposed method.
A foresight study on urban mobility: Singapore in 2040
Authors: Zahraei Seyed Mehdi , Kurniawan Jude Herijadi , Cheah Lynette
Published: November 2019

Purpose

The transportation system in any city is complex and evolving, shaped by various driving forces and uncertainties in the social, economic, technological, political and environmental situations. Its development and demands upon it cannot be projected by simply extrapolating past and current trends. This paper aims to present a foresight study examining the future of urban mobility, focusing on the dense Asian city-state of Singapore. The objective is to develop scenarios for the future of urban mobility, to facilitate future policy implementation by highlighting long term challenges and opportunities for transportation planning in cities.

Design/methodology/approach

To create future scenarios, the authors first sought to identify key drivers of change through environmental scanning, expert interviews, focus group discussions and technology scanning. These drivers of change were subsequently used in a scenario planning workshop, organized to co-create alternative future visions for urban mobility 2040 with experts and local stakeholders.

Findings

Two scenarios emerged, called the Shared World and the Virtual World. For each scenario, the authors described the key features in terms of dominant transport modes for the movements of passengers and freight. Subsequently, the authors discussed possible implications of each scenario to the individual, society, industry and government.

Originality/value

As cities grow and develop, city and transport planners should not only address daily operational issues but also develop a well-informed, long-term understanding of the evolving mobility system to address challenges that lie beyond the five- or even ten-year horizon. By using scenario planning approach, the authors hope to prepare stakeholders for the uncertain futures that are continuously shaped by the decisions today.
Evaluating a guest satisfaction model through data mining
Authors: Moro Sérgio , Esmerado Joaquim , Ramos Pedro , Alturas Bráulio
Published: November 2019

Purpose

This paper aims to propose a data mining approach to evaluate a conceptual model in tourism, encompassing a large data set characterized by dimensions grounded on existing literature.

Design/methodology/approach

The approach is tested using a guest satisfaction model encompassing nine dimensions. A large data set of 84 k online reviews and 31 features was collected from TripAdvisor. The review score granted was considered a proxy of guest satisfaction and was defined as the target feature to model. A sequence of data understanding and preparation tasks led to a tuned set of 60k reviews and 29 input features which were used for training the data mining model. Finally, the data-based sensitivity analysis was adopted to understand which dimensions most influence guest satisfaction.

Findings

Previous user’s experience with the online platform, individual preferences, and hotel prestige were the most relevant dimensions concerning guests’ satisfaction. On the opposite, homogeneous characteristics among the Las Vegas hotels such as the hotel size were found of little relevance to satisfaction.

Originality/value

This study intends to set a baseline for an easier adoption of data mining to evaluate conceptual models through a scalable approach, helping to bridge between theory and practice, especially relevant when dealing with Big Data sources such as the social media. Thus, the steps undertaken during the study are detailed to facilitate replication to other models.
Lesson study with didactical engineering for student teachers in Brazil
Authors: de Macedo Aluska Dias Ramos , Baltar Bellemain Paula Moreira , Winsløw Carl
Published: November 2019

Purpose

The purpose of this paper is to experiment with ideas from didactical engineering (DE) in student teachers’ first experience with lesson study (LS).

Design/methodology/approach

This is a case study.

Findings

LS in pre-service education can be enhanced by elements from DE.

Originality/value

The idea indicated in the purpose is new and holds strong potential for the use of LS in teacher education.