bluuebunny/crossref_metadata_2025 huggingface dataset:
Geographical Differentiation of Greek Extra Virgin Olive Oil from Late‐Harvested Koroneiki Cultivar Fruits
Authors: Kosma Ioanna , Vatavali Kornilia , Kontakos Stavros , Kontominas Michael , Kiritsakis Apostolos , Badeka Anastasia
Published: September 2017

Seventy‐four monovarietal olive oil samples belonging to the Koroneiki cultivar were collected from four selected olive oil‐producing regions of Greece (Messinia, Lakonia, Irakleio and Etoloakarnania), during two harvesting periods (2012/2013 and 2013/2014) at the stage of full maturation (maturation index 5–6). Determination of volatile compounds (VC), fatty acid (FA) composition, total phenolic content (TPC) and color parameters was carried out in an effort to classify Koroneiki olive oil samples according to geographical origin, while conventional quality parameters (CQP) were used to characterize the samples. The analytical data were then subjected to statistical analysis using multivariate analysis of variance (MANOVA) and linear discriminant analysis (LDA). The results showed a correct classification rate of 79.7% based on VC analysis, 81.1% based on the combination of VC analysis and FA composition, and 87.8% based on the combination of VC analysis and color parameters.
Mesoporous silica-based nanoplatforms for the delivery of photodynamic therapy agents
Authors: Hong Suk ho , Choi Yongdoo
Published: September 2017

Photodynamic therapy (PDT) is an established method for the treatment of cancer which utilizes light, a photosensitizer (PS), and oxygen. Unfavourable characteristics of most PSs, such as low solubility and tumour specificity have led many researchers to adopt nanoscale drug delivery platforms for use in PDT. Mesoporous silica nanoparticles (MSNs) form a significant part of that effort, due to their ease and controllability of synthesis, ease of loading, availability of diverse surface functionalization, and biocompatibility. Therefore, in this review, we discuss the properties of MSNs as they pertain to their use in PDT and review the latest advances in the field, comparing the different approaches currently being used.
Brief report: A network analysis of self‐cutting risk among late adolescent girls exposed to dating violence
Authors: Gittins Stone Daniel Ian , DuBois Russell , DeJesus Brett , Rodgers Rachel F. , Rizzo Christie
Published: September 2017

Adolescent self‐directed violence (SDV) is a major public health concern. Adolescent girls exposed to dating violence (DV) are a particularly vulnerable group. Numerous studies have examined the number and type of SDV risk factors, but few examined global patterns of relationships among them. Exploring global patterns of risk is crucial to developing targeted prevention efforts. In this study we applied a network model to identify risk patterns for a common form of SDV, self‐cutting, among American adolescent girls (N = 109) with history of DV. Risk factor networks were compared among girls who did/did not endorse lifetime self‐cutting. Girls with a history of self‐cutting (19%) had a risk factor network characterized by a higher number of associations than girls who did not (test statistic = 0.142; 95% CI = 02‐.03). For these girls, the experience of one risk factor is more likely to co‐occur with multiple others, thereby potentially compounding effects and unwanted consequences.
A Brief History of Economic Thought
Authors: Roncaglia Alessandro
Published: September 2017

The evolution of economic thought can be traced back from its beginnings in classical antiquity up to the present day. In this book, Professor Alessandro Roncaglia offers a clear, concise and updated version of his award-winning The Wealth of Ideas, studying the development of economic thought through perspectives and debates on the economy and society over time. With chapters on prominent economic theorists, including William Petty, Karl Marx, and John Maynard Keynes, as well as on other important figures and key debates of each period, Roncaglia critically evaluates the foundations of the marginalist–neoclassical (scarcity–utility) approach in comparison to the Classical–Keynes approach. A comprehensive guide to the history of economic thought, this book will be of value not only to undergraduate and postgraduate students studying economic thought, but also to any readers desiring to study how economics has evolved up to the present day.
The Health-Security Nexus and the European Union: Toward a Research Agenda
Authors: DIJKSTRA Hylke , DE RUIJTER Anniek
Published: September 2017

The European Union is increasingly moving toward an integrated policy approach, which also acknowledges linkages between public health and (external) security policy. This introduction to the Special Issue sets out a research agenda on the emerging health-security nexus. It analyses recent policy developments with respect to the public health and security, and discusses interactions along the health-security nexus in the context of the European Union. It suggests drivers behind the integrated approach and it critically examines the health-security nexus from the perspective of effectiveness and legitimacy.
Capital as Process and the History of Capitalism
Authors: Levy Jonathan
Published: September 2017

In the wake of the Great Recession, a new cycle of scholarship opened on the history of American capitalism. This occurred, however, without much specification of the subject at hand. In this essay, I offer a conceptualization of capitalism, by focusing on its root—capital. Much historical writing has treated capital as a physical factor of production. Against such a “materialist” capital concept, I define capital as a pecuniary process of forward-looking valuation, associated with investment. Engaging recent work across literatures, I try to show how this conceptualization of capital and capitalism helps illuminate many core dynamics of modern economic life.
The Moral Law as a Fact of Reason and Correctness Conditions for the Moral Law
Authors: LEE BYEONG D.
Published: September 2017

In the second Critique, Kant claims that the moral law is given as a fact of reason. In this paper, contra the standard view, I argue that there is a non-dogmatic way of defending this claim. And Kant’s principle of morality is widely taken to be a formal principle. How then can such a formal principle be reconciled with our substantial moral end? In this paper, I also argue that Kant’s principle of morality can be construed as a formal principle in the sense that it provides correctness conditions for moral laws, rather than providing specific moral laws.
Signatures of quantum effects on radiation reaction in laser–electron-beam collisions
Authors: Ridgers C. P. , Blackburn T. G. , Del Sorbo D. , Bradley L. E. , Slade-Lowther C. , Baird C. D. , Mangles S. P. D. , McKenna P. , Marklund M. , Murphy C. D. , Thomas A. G. R.
Published: September 2017

Two signatures of quantum effects on radiation reaction in the collision of a ${\sim}$GeV electron beam with a high intensity (${>}3\times 10^{20}~\text{W}~\text{cm}^{-2}$) laser pulse have been considered. We show that the decrease in the average energy of the electron beam may be used to measure the Gaunt factor $g$ for synchrotron emission. We derive an equation for the evolution of the variance in the energy of the electron beam in the quantum regime, i.e. quantum efficiency parameter $\unicode[STIX]{x1D702}\not \ll 1$. We show that the evolution of the variance may be used as a direct measure of the quantum stochasticity of the radiation reaction and determine the parameter regime where this is observable. For example, stochastic emission results in a 25 % increase in the standard deviation of the energy spectrum of a GeV electron beam, 1 fs after it collides with a laser pulse of intensity $10^{21}~\text{W}~\text{cm}^{-2}$. This effect should therefore be measurable using current high-intensity laser systems.
Parasites ofScyliorhinus canicula(Linnaeus, 1758) in the north-eastern Aegean Sea
Authors: Bakopoulos Vasileios , Tsepa Euaggelia , Diakou Anastasia , Kokkoris Giorgos , Kolygas Markos Nikolaos , Athanassopoulou Foteini
Published: September 2017

The parasitic fauna of the small-spotted catshark,Scyliorhinus caniculain the north-eastern Aegean Sea was investigated. Twenty-one out of the 52 (prevalence 40.4%) specimens collected were found infected with parasites; an arthropod and two nematode genera. Seven specimens (prevalence 13.5%) were infected by aNeoalbionellasp. copepod. Ten and 14 specimens were infected by the nematodesProleptus obtusus(prevalence 19.2%) andAnisakissp. (prevalence 26.9%), respectively. FemaleS. caniculaspecimens were significantly more heavily infected during autumn and when the whole sampling period is considered. Nematode infection was significantly related to season, becoming progressively heavier from spring to autumn. No correlation was found between TL of specimens and number of parasites for males or females, irrespective of gender. The present study provided a first record ofNeoalbionellasp.,P. obtususandAnisakissp. infections ofS. caniculain the north-eastern Mediterranean. The lower prevalence ofProleptus obtususand the higher prevalence ofAnisakissp. infection recorded in this study may be due to prey availability and parasite populations in this locality.
Leukocyte telomere length and personality: associations with the Big Five and Type D personality traits
Authors: Schoormans D. , Verhoeven J. E. , Denollet J. , van de Poll-Franse L. , Penninx B. W. J. H.
Published: September 2017

Backgrounds

Accelerated cellular ageing, which can be examined by telomere length (TL), may be an overarching mechanism underlying the association between personality and adverse health outcomes. This 6-year longitudinal study examined the relation between personality and leukocyte telomere length (LTL) across time among adults with a wide age-range.

Methods

Data from the Netherlands Study of Depression and Anxiety were used and included patients with a depression and/or anxiety disorder and healthy controls. Overall, 2936 persons (18–65 years, 66% female) had data on LTL at baseline and 1883 persons had LTL at 6-year follow-up. The Big Five personality traits (neuroticism, extraversion, openness to experience, agreeableness, and conscientiousness) and Type D personality were assessed.

Results

Neuroticism was negatively (B = −2.11, p = 0.03) and agreeableness was positively (B = 3.84, p = 0.03) related to LTL measured across two time points, which became just non-significant after adjusting for somatic health, lifestyle factors, and recent life stress (B = −1.99, p = 0.06; and B = 3.01, p = 0.10). Type D personality was negatively (B = −50.16, p < 0.01) related to LTL across two time points, which still remained statistically significant after full adjustment (B = −47.37, p = 0.01). Associations did not differ by age, gender, and current psychiatric status.

Conclusions

The Big Five traits high neuroticism and low agreeableness, and Type D personality were associated with shorter LTL measured across a 6-year period. Associations with the Big Five traits became non-significant after controlling for somatic health, lifestyle factors, and recent life stress, yet similar trends were observed. Type D personality remained independently associated with shorter LTL after full adjustment.
Distinguishing postpartum and antepartum depressive trajectories in a large population-based cohort: the impact of exposure to adversity and offspring gender
Authors: Denckla C. A. , Mancini A. D. , Consedine N. S. , Milanovic S. M. , Basu A. , Seedat S. , Spies G. , Henderson D. C. , Bonanno G. A. , Koenen K. C.
Published: September 2017

Background

Distinguishing temporal patterns of depressive symptoms during pregnancy and after childbirth has important clinical implications for diagnosis, treatment, and maternal and child outcomes. The primary aim of the present study was to distinguish patterns of chronically elevated levels of depressive symptoms v. trajectories that are either elevated during pregnancy but then remit after childbirth, v. patterns that increase after childbirth.

Methods

The report uses latent growth mixture modeling in a large, population-based cohort (N = 12 121) to investigate temporal patterns of depressive symptoms. We examined theoretically relevant sociodemographic factors, exposure to adversity, and offspring gender as predictors.

Results

Four distinct trajectories emerged, including resilient (74.3%), improving (9.2%), emergent (4.0%), and chronic (11.5%). Lower maternal and paternal education distinguished chronic from resilient depressive trajectories, whereas higher maternal and partner education, and female offspring gender, distinguished the emergent trajectory from the chronic trajectory. Younger maternal age distinguished the improving group from the resilient group. Exposure to medical, interpersonal, financial, and housing adversity predicted membership in the chronic, emergent, and improving trajectories compared with the resilient trajectory. Finally, exposure to medical, interpersonal, and financial adversity was associated with the chronic v. improving group, and inversely related to the emergent class relative to the improving group.

Conclusions

There are distinct temporal patterns of depressive symptoms during pregnancy, after childbirth, and beyond. Most women show stable low levels of depressive symptoms, while emergent and chronic depression patterns are separable with distinct correlates, most notably maternal age, education levels, adversity exposure, and child gender.
Unsettling race and language: Toward a raciolinguistic perspective
Authors: Rosa Jonathan , Flores Nelson
Published: September 2017

This article presents what we term araciolinguistic perspective, which theorizes the historical and contemporary co-naturalization of language and race. Rather than taking for granted existing categories for parsing and classifying race and language, we seek to understand how and why these categories have been co-naturalized, and to imagine their denaturalization as part of a broader structural project of contesting white supremacy. We explore five key components of a raciolinguistic perspective: (i) historical and contemporary colonial co-naturalizations of race and language; (ii) perceptions of racial and linguistic difference; (iii) regimentations of racial and linguistic categories; (iv) racial and linguistic intersections and assemblages; and (v) contestations of racial and linguistic power formations. These foci reflect our investment in developing a careful theorization of various forms of racial and linguistic inequality on the one hand, and our commitment to the imagination and creation of more just societies on the other. (Race, language ideologies, colonialism, governmentality, enregisterment, structural inequality)*
‘Gregory Dry’: Parody and the morality of brand
Authors: Kohler Gregory
Published: September 2017

While Bakhtin's (1981) notions of voicing, double voicing, and ventriloquation have been applied extensively in linguistic anthropology and sociolinguistics, only a few scholars have engaged with his related notion of parody. This article examines how a Sardinian manager uses parody in an oral narrative to construct and contest moralities surrounding personal and corporate identities. Through an analysis of both the story and the storytelling event, I show how this manager uses parody to better align himself with the ideals of his company and to frame his relationships with his employers and with the market more generally. In particular, my analysis focuses on how managers discursively create moral hierarchies of value that become key resources for understanding their stance in relation to the competitive dynamics of their industries. Parody in storytelling thus proves to be a crucial analytical tool for understanding brand and branding strategies. (Parody, narrative, brand, Italy, discourse analysis)*
Canadian policy perspectives on promoting physical activity across age-friendly communities: lessons for advocacy and action
Authors: NYKIFORUK CANDACE I. J. , RAWSON DEBORAH , MCGETRICK JENNIFER ANN , BELON ANA PAULA
Published: September 2017

Population ageing combined with physical inactivity has critical implications for the public health of communities in the twenty-first century. In the last decade, the World Health Organization launched the age-friendly cities agenda, aiming to address population ageing through whole-systems, rights-based, health equity-focused approaches. An important intervention for age-friendly communities is modifying built environments to support population-level physical activity. Physical activity can help mitigate impacts of chronic diseases and social isolation on older adults. Need for advocacy and action in this area raises questions of how to develop supportive environments for physical activity across age-friendly community types. In Canada, a substantial proportion of older adults live outside large urban municipalities, for which scant research exists on fostering age-friendly built environments. To this end, we conducted qualitative research involving semi-structured interviews with 21 municipal policy influencers in Alberta, Canada to gather perspectives on development and early implementation of an age-friendly policy framework in the small urban and rural context. Our findings are organised by three main themes providing key lessons for advocacy and action, namelypursuing comprehensive planning,promoting public engagementandprioritising the needs of older adults. This research informs advocacy and action priorities in promoting built environment modification for routine physical activity as part of an age-friendliness agenda for small urban and rural regions of Canada and other countries.
Cardiovascular CT for evaluation of single-ventricle heart disease: risks and accuracy compared with interventional findings
Authors: Han B. Kelly , Huntley Marnie , Overman David , Witt Dawn , Dassenko David , Garberich Ross F. , Lesser John R.
Published: September 2017

Objective

We sought to evaluate the risk and image quality from cardiovascular CT in patients across all stages of single-ventricle palliation, and to define accuracy by comparing findings with intervention and surgery.

Methods

Consecutive CT scans performed in patients with single-ventricle heart disease were retrospectively reviewed at a single institution. Diagnosis, sedation needs, estimated radiation dose, and adverse events were recorded. Anatomical findings, image quality (1–4, 1=optimal), and discrepancy compared with interventional findings were determined. Results are described as medians with their 25th and 75th percentiles.

Results

From January, 2010 to August, 2015, 132 CT scans were performed in single-ventricle patients of whom 20 were neonates, 52 were post-Norwood, 15 were post-Glenn, and 45 were post-Fontan. No sedation was used in 76 patients, 47 were under minimal or moderate sedation, and nine were under general anaesthesia. The median image quality score was 1.2. The procedural dose–length product was 24 mGy-cm, and unadjusted and adjusted radiation doses were 0.34 (0.2, 1.8) and 0.82 (0.55, 1.88) mSv, respectively. There was one adverse event. No major and two minor discrepancies were noted at the time of 79 surgical and 10 catheter-based interventions.

Conclusions

Cardiovascular CT can be performed with a low radiation exposure in patients with single-ventricle heart disease. Its accuracy compared with that of interventional findings is excellent. CT is an effective advanced imaging modality when a non-invasive pathway is desired, particularly if cardiac MRI poses a high risk or is contraindicated.
NF-κB pathway link with ER stress-induced autophagy and apoptosis in cervical tumor cells
Authors: Zhu Xiaolan , Huang Li , Gong Jie , Shi Chun , Wang Zhiming , Ye Bingkun , Xuan Aiguo , He Xiaosong , Long Dahong , Zhu Xiao , Ma Ningfang , Leng Shuilong
Published: September 2017

Targeting endoplasmic reticulum (ER) stress is being investigated for its anticancer effect in various cancers, including cervical cancer. However, the molecular pathways whereby ER stress mediates cell death remain to be fully elucidated. In this study, we confirmed that ER stress triggered by compounds such as brefeldin A (BFA), tunicamycin (TM), and thapsigargin (TG) leads to the induction of the unfolded protein response (UPR) in cervical cancer cell lines, which is characterized by elevated levels of inositol-requiring kinase 1α, glucose-regulated protein-78, and C/EBP homologous protein, and swelling of the ER observed by transmission electron microscope (TEM). We found that BFA significantly increased autophagy in tumor cells and induced TC-1 tumor cell death in a dose-dependent manner. BFA increased punctate staining of LC3 and the number of autophagosomes observed by TEM in TC-1 and HeLa cells. The autophagic flux was also assessed. Bafilomycin, which blocked degradation of LC3 in lysosomes, caused both LC3I and LC3II accumulation. BFA initiated apoptosis of TC-1 tumor cells through activation of the caspase-12/caspase-3 pathway. At the same time, BFA enhanced the phosphorylation of IκBαprotein and translocation into the nucleus of NF-κB p65. Quinazolinediamine, an NF-κB inhibitor, attenuated both autophagy and apoptosis induced by BFA; meanwhile, it partly enhances survival of cervical cancer cells following BFA treatment. In conclusion, our results indicate that the cross-talk between ER stress, autophagy, apoptosis, and the NF-κB pathways controls the fate of cervical cancer cells. Careful evaluation should be given to the addition of an NF-κB pathway inhibitor to treat cervical cancer in combination with drugs that induce ER stress-mediated cell death.
Prdx6 retards senescence and restores trabecular meshwork cell health by regulating reactive oxygen species
Authors: Chhunchha Bhavana , Singh Prerna , Stamer W Daniel , Singh Dhirendra P
Published: September 2017

A progressive decline in antioxidant potential and accumulation of reactive oxygen species (ROS) are major causes of pathogenesis of several diseases, including glaucoma. Trabecular meshwork (TM) dysfunction resulting in higher intraocular pressure (IOP) is a hallmark of glaucoma, but its causes are unclear. Using human (h) TM cells derived from glaucomatous and normal subjects of different ages and cells facing oxidative-stress, we showed that specific loss of moonlighting antioxidant protein Peroxiredoxin (Prdx) 6 in aging or in glaucomatous TM cells caused ROS accumulation and pathobiological changes in TM cells. Prdx6 limits the levels of ROS, thus preventing overstimulation of genes and resultant deleterious effects. We found that Prdx6 levels declined in aging and were reduced dramatically in glaucomatous and aged TM cells. Biochemical assays revealed enhanced levels of ROS, and high expression/activation of TGFβs and its responsive extracellular matrix genes α-SM, fibronectin, TGase2 and Tsp1 in aged or glaucomatous cells. Furthermore, hTM cells displayed typical features of the combined effects of TGFβs and oxidative-stress-induced cellular changes, showing increased levels of lipid peroxidation, oxidative DNA damage, and senescence markers p16, p21 and SA-βgal activity, along with reduced levels of telomerase expression and activity. Exposure to oxidative-stress (H2O2) or knocking down of Prdx6 (with antisense) accelerated this process. Importantly, Prdx6 delivery to sick or aged TM cells reversed the process. We propose Prdx6 as a potential therapeutic target to guard the TM from oxidative-stress and age-dependent accumulation of ROS by balancing redox-homeostasis to prevent ocular disorders, like glaucoma.
Tia1 dependent regulation of mRNA subcellular location and translation controls p53 expression in B cells
Authors: Díaz-Muñoz Manuel D. , Kiselev Vladimir Yu. , Le Novère Nicolas , Curk Tomaz , Ule Jernej , Turner Martin
Published: September 2017

Post-transcriptional regulation of cellular mRNA is essential for protein synthesis. Here we describe the importance of mRNA translational repression and mRNA subcellular location for protein expression during B lymphocyte activation and the DNA damage response. Cytoplasmic RNA granules are formed upon cell activation with mitogens, including stress granules that contain the RNA binding protein Tia1. Tia1 binds to a subset of transcripts involved in cell stress, including p53 mRNA, and controls translational silencing and RNA granule localization. DNA damage promotes mRNA relocation and translation in part due to dissociation of Tia1 from its mRNA targets. Upon DNA damage, p53 mRNA is released from stress granules and associates with polyribosomes to increase protein synthesis in a CAP-independent manner. Global analysis of cellular mRNA abundance and translation indicates that this is an extended ATM-dependent mechanism to increase protein expression of key modulators of the DNA damage response.
Identifying topologically associating domains and subdomains by Gaussian Mixture model And Proportion test
Authors: Yu Wenbao , He Bing , Tan Kai
Published: September 2017

The spatial organization of the genome plays a critical role in regulating gene expression. Recent chromatin interaction mapping studies have revealed that topologically associating domains and subdomains are fundamental building blocks of the three-dimensional genome. Identifying such hierarchical structures is a critical step toward understanding the three-dimensional structure–function relationship of the genome. Existing computational algorithms lack statistical assessment of domain predictions and are computationally inefficient for high-resolution Hi-C data. We introduce the Gaussian Mixture model And Proportion test (GMAP) algorithm to address the above-mentioned challenges. Using simulated and experimental Hi-C data, we show that domains identified by GMAP are more consistent with multiple lines of supporting evidence than three state-of-the-art methods. Application of GMAP to normal and cancer cells reveals several unique features of subdomain boundary as compared to domain boundary, including its higher dynamics across cell types and enrichment for somatic mutations in cancer.
Ampk phosphorylation of Ulk1 is required for targeting of mitochondria to lysosomes in exercise-induced mitophagy
Authors: Laker Rhianna C. , Drake Joshua C. , Wilson Rebecca J. , Lira Vitor A. , Lewellen Bevan M. , Ryall Karen A. , Fisher Carleigh C. , Zhang Mei , Saucerman Jeffrey J. , Goodyear Laurie J. , Kundu Mondira , Yan Zhen
Published: September 2017

Mitochondrial health is critical for skeletal muscle function and is improved by exercise training through both mitochondrial biogenesis and removal of damaged/dysfunctional mitochondria via mitophagy. The mechanisms underlying exercise-induced mitophagy have not been fully elucidated. Here, we show that acute treadmill running in mice causes mitochondrial oxidative stress at 3–12 h and mitophagy at 6 h post-exercise in skeletal muscle. These changes were monitored using a novel fluorescent reporter gene, pMitoTimer, that allows assessment of mitochondrial oxidative stress and mitophagy in vivo, and were preceded by increased phosphorylation of AMP activated protein kinase (Ampk) at tyrosine 172 and of unc-51 like autophagy activating kinase 1 (Ulk1) at serine 555. Using mice expressing dominant negative and constitutively active Ampk in skeletal muscle, we demonstrate that Ulk1 activation is dependent on Ampk. Furthermore, exercise-induced metabolic adaptation requires Ulk1. These findings provide direct evidence of exercise-induced mitophagy and demonstrate the importance of Ampk-Ulk1 signaling in skeletal muscle.
Complete fusion of a transposon and herpesvirus created the Teratorn mobile element in medaka fish
Authors: Inoue Yusuke , Saga Tomonori , Aikawa Takumi , Kumagai Masahiko , Shimada Atsuko , Kawaguchi Yasushi , Naruse Kiyoshi , Morishita Shinichi , Koga Akihiko , Takeda Hiroyuki
Published: September 2017

Mobile genetic elements (e.g., transposable elements and viruses) display significant diversity with various life cycles, but how novel elements emerge remains obscure. Here, we report a giant (180-kb long) transposon, Teratorn, originally identified in the genome of medaka, Oryzias latipes. Teratorn belongs to the piggyBac superfamily and retains the transposition activity. Remarkably, Teratorn is largely derived from a herpesvirus of the Alloherpesviridae family that could infect fish and amphibians. Genomic survey of Teratorn-like elements reveals that some of them exist as a fused form between piggyBac transposon and herpesvirus genome in teleosts, implying the generality of transposon-herpesvirus fusion. We propose that Teratorn was created by a unique fusion of DNA transposon and herpesvirus, leading to life cycle shift. Our study supports the idea that recombination is the key event in generation of novel mobile genetic elements.
Understanding CRY2 interactions for optical control of intracellular signaling
Authors: Duan Liting , Hope Jen , Ong Qunxiang , Lou Hsin-Ya , Kim Namdoo , McCarthy Comfrey , Acero Victor , Lin Michael Z. , Cui Bianxiao
Published: September 2017

Arabidopsis cryptochrome 2 (CRY2) can simultaneously undergo light-dependent CRY2–CRY2 homo-oligomerization and CRY2–CIB1 hetero-dimerization, both of which have been widely used to optically control intracellular processes. Applications using CRY2–CIB1 interaction desire minimal CRY2 homo-oligomerization to avoid unintended complications, while those utilizing CRY2–CRY2 interaction prefer robust homo-oligomerization. However, selecting the type of CRY2 interaction has not been possible as the molecular mechanisms underlying CRY2 interactions﻿ are unknown. Here we report CRY2–CIB1 and CRY2–CRY2 interactions are governed by well-separated protein interfaces at the two termini of CRY2. N-terminal charges are critical for CRY2–CIB1 interaction. Moreover, two C-terminal charges impact CRY2 homo-oligomerization, with positive charges facilitating oligomerization and negative charges inhibiting it. By engineering C-terminal charges, we develop CRY2high and CRY2low with elevated or suppressed oligomerization respectively, which we use to tune the levels of Raf/MEK/ERK signaling. These results contribute to our understanding of the mechanisms underlying light-induced CRY2 interactions and enhance the controllability of CRY2-based optogenetic systems.
A rechargeable iodine-carbon battery that exploits ion intercalation and iodine redox chemistry
Authors: Lu Ke , Hu Ziyu , Ma Jizhen , Ma Houyi , Dai Liming , Zhang Jintao
Published: September 2017

Graphitic carbons have been used as conductive supports for developing rechargeable batteries. However, the classic ion intercalation in graphitic carbon has yet to be coupled with extrinsic redox reactions to develop rechargeable batteries. Herein, we demonstrate the preparation of a free-standing, flexible nitrogen and phosphorus co-doped hierarchically porous graphitic carbon for iodine loading by pyrolysis of polyaniline coated cellulose wiper. We find that heteroatoms could provide additional defect sites for encapsulating iodine while the porous carbon skeleton facilitates redox reactions of iodine and ion intercalation. The combination of ion intercalation with redox reactions of iodine allows for developing rechargeable iodine–carbon batteries free from the unsafe lithium/sodium metals, and hence eliminates the long-standing safety issue. The unique architecture of the hierarchically porous graphitic carbon with heteroatom doping not only provides suitable spaces for both iodine encapsulation and cation intercalation but also generates efficient electronic and ionic transport pathways, thus leading to enhanced performance.
A CRISPR screen identifies genes controlling Etv2 threshold expression in murine hemangiogenic fate commitment
Authors: Zhao Haiyong , Choi Kyunghee
Published: September 2017

The ETS transcription factor Etv2 is necessary and sufficient for the generation of hematopoietic and endothelial cells. However, upstream regulators of Etv2 in hemangiogenesis, generation of hematopoietic and endothelial cells, have not been clearly addressed. Here we track the developmental route of hemangiogenic progenitors from mouse embryonic stem cells, perform genome-wide CRISPR screening, and transcriptome analysis of en route cell populations by utilizing Brachyury, Etv2, or Scl reporter embryonic stem cell lines to further understand the mechanisms that control hemangiogenesis. We identify the forkhead transcription factor Foxh1, in part through Eomes, to be critical for the formation of FLK1+ mesoderm, from which the hemangiogenic fate is specified. Importantly, hemangiogenic fate is specified not simply by the onset of Etv2 expression, but by a threshold-dependent mechanism, in which VEGF-FLK1 signaling plays an instructive role by promoting Etv2 threshold expression. These studies reveal comprehensive cellular and molecular pathways governing the hemangiogenic cell lineage development.
The Ino80 complex mediates epigenetic centromere propagation via active removal of histone H3
Authors: Choi Eun Shik , Cheon Youngseo , Kang Keunsoo , Lee Daeyoup
Published: September 2017

The centromere is the chromosomal locus at which the kinetochore is assembled to direct chromosome segregation. The histone H3 variant, centromere protein A (CENP-A), is known to epigenetically mark active centromeres, but the mechanism by which CENP-A propagates at the centromere, replacing histone H3, remains poorly understood. Using fission yeast, here we show that the Ino80 adenosine triphosphate (ATP)-dependent chromatin-remodeling complex, which removes histone H3-containing nucleosomes from associated chromatin, promotes CENP-ACnp1 chromatin assembly at the centromere in a redundant manner with another chromatin-remodeling factor Chd1Hrp1. CENP-ACnp1 chromatin actively recruits the Ino80 complex to centromeres to elicit eviction of histone H3-containing nucleosomes. Artificial targeting of Ino80 subunits to a non-centromeric DNA sequence placed in a native centromere enhances the spreading of CENP-ACnp1 chromatin into the non-centromeric DNA. Based on these results, we propose that CENP-ACnp1 chromatin employs the Ino80 complex to mediate the replacement of histone H3 with CENP-ACnp1, and thereby reinforces itself.
Muscle pathology from stochastic low level DUX4 expression in an FSHD mouse model
Authors: Bosnakovski Darko , Chan Sunny S. K. , Recht Olivia O. , Hartweck Lynn M. , Gustafson Collin J. , Athman Laura L. , Lowe Dawn A. , Kyba Michael
Published: September 2017

Facioscapulohumeral muscular dystrophy is a slowly progressive but devastating myopathy caused by loss of repression of the transcription factor DUX4; however, DUX4 expression is very low, and protein has not been detected directly in patient biopsies. Efforts to model DUX4 myopathy in mice have foundered either in being too severe, or in lacking muscle phenotypes. Here we show that the endogenous facioscapulohumeral muscular dystrophy-specific DUX4 polyadenylation signal is surprisingly inefficient, and use this finding to develop an facioscapulohumeral muscular dystrophy mouse model with muscle-specific doxycycline-regulated DUX4 expression. Very low expression levels, resulting in infrequent DUX4 + myonuclei, evoke a slow progressive degenerative myopathy. The degenerative process involves inflammation and a remarkable expansion in the fibroadipogenic progenitor compartment, leading to fibrosis. These animals also show high frequency hearing deficits and impaired skeletal muscle regeneration after injury. This mouse model will facilitate in vivo testing of therapeutics, and suggests the involvement of fibroadipogenic progenitors in facioscapulohumeral muscular dystrophy.
An HDAC3-PROX1 corepressor module acts on HNF4α to control hepatic triglycerides
Authors: Armour Sean M. , Remsberg Jarrett R. , Damle Manashree , Sidoli Simone , Ho Wesley Y. , Li Zhenghui , Garcia Benjamin A. , Lazar Mitchell A.
Published: September 2017

The histone deacetylase HDAC3 is a critical mediator of hepatic lipid metabolism, and liver-specific deletion of HDAC3 leads to fatty liver. To elucidate the underlying mechanism, here we report a method of cross-linking followed by mass spectrometry to define a high-confidence HDAC3 interactome in vivo that includes the canonical NCoR–HDAC3 complex as well as Prospero-related homeobox 1 protein (PROX1). HDAC3 and PROX1 co-localize extensively on the mouse liver genome, and are co-recruited by hepatocyte nuclear factor 4α (HNF4α). The HDAC3–PROX1 module controls the expression of a gene program regulating lipid homeostasis, and hepatic-specific ablation of either component increases triglyceride content in liver. These findings underscore the importance of specific combinations of transcription factors and coregulators in the fine tuning of organismal metabolism.
Invasive Andropogon gayanus (Gamba grass) alters litter decomposition and nitrogen fluxes in an Australian tropical savanna
Authors: Rossiter-Rachor N. A. , Setterfield S. A. , Hutley L. B. , McMaster D. , Schmidt S. , Douglas M. M.
Published: September 2017

The African grass Andropogon gayanus Kunth. is invading Australian savannas, altering their ecological and biogeochemical function. To assess impacts on nitrogen (N) cycling, we quantified litter decomposition and N dynamics of grass litter in native grass and A. gayanus invaded savanna using destructive in situ grass litter harvests and litterbag incubations (soil surface and aerial position). Only 30% of the A. gayanus in situ litter decomposed, compared to 61% of the native grass litter, due to the former being largely comprised of highly resistant A. gayanus stem. In contrast to the stem, A. gayanus leaf decomposition was approximately 3- and 2-times higher than the dominant native grass, Alloteropsis semilata at the surface and aerial position, respectively. Lower initial lignin concentrations, and higher consumption by termites, accounted for the greater surface decomposition rate of A. gayanus. N flux estimates suggest the N release of A. gayanus litter is insufficient to compensate for increased N uptake and N loss via fire in invaded plots. Annually burnt invaded savanna may lose up to 8.2% of the upper soil N pool over a decade. Without additional inputs via biological N fixation, A. gayanus invasion is likely to diminish the N capital of Australia’s frequently burnt savannas.
Multidimensional encoding of brain connectomes
Authors: Caiafa Cesar F. , Pestilli Franco
Published: September 2017

The ability to map brain networks in living individuals is fundamental in efforts to chart the relation between human behavior, health and disease. Advances in network neuroscience may benefit from developing new frameworks for mapping brain connectomes. We present a framework to encode structural brain connectomes and diffusion-weighted magnetic resonance (dMRI) data using multidimensional arrays. The framework integrates the relation between connectome nodes, edges, white matter fascicles and diffusion data. We demonstrate the utility of the framework forin vivowhite matter mapping and anatomical computing by evaluating 1,490 connectomes, thirteen tractography methods, and three data sets. The framework dramatically reduces storage requirements for connectome evaluation methods, with up to 40x compression factors. Evaluation of multiple, diverse datasets demonstrates the importance of spatial resolution in dMRI. We measured large increases in connectome resolution as function of data spatial resolution (up to 52%). Moreover, we demonstrate that the framework allows performing anatomical manipulations on white matter tracts for statistical inference and to study the white matter geometrical organization. Finally, we provide open-source software implementing the method and data to reproduce the results.
Synthesis of flower-like magnetite nanoassembly: Application in the efficient reduction of nitroarenes
Authors: Datta Kasibhatta J. , Rathi Anuj K. , Kumar Pawan , Kaslik Josef , Medrik Ivo , Ranc Vaclav , Varma Rajender S. , Zboril Radek , Gawande Manoj B.
Published: September 2017

A facile approach for the synthesis of magnetite microspheres with flower-like morphology is reported that proceeds via the reduction of iron(III) oxide under a hydrogen atmosphere. The ensuing magnetic catalyst is well characterized by XRD, FE-SEM, TEM, N2 adsorption-desorption isotherm, and Mössbauer spectroscopy and explored for a simple yet efficient transfer hydrogenation reduction of a variety of nitroarenes to respective anilines in good to excellent yields (up to 98%) employing hydrazine hydrate. The catalyst could be easily separated at the end of a reaction using an external magnet and can be recycled up to 10 times without any loss in catalytic activity.
Identification of sites of 2′-O-methylation vulnerability in human ribosomal RNAs by systematic mapping
Authors: Sharma Sunny , Marchand Virginie , Motorin Yuri , Lafontaine Denis L. J.
Published: September 2017

Ribosomal RNA modifications are important in optimizing ribosome function. Sugar 2′-O-methylation performed by fibrillarin-associated box C/D antisense guide snoRNAs impacts all steps of translation, playing a role in disease etiology (cancer). As it renders adjacent phosphodiester bonds resistant to alkaline treatment, 2′-O-methylation can be monitored qualitatively and quantitatively by applying next-generation sequencing to fragments of randomly cleaved RNA. We remapped all sites of 2′-O-methylation in human rRNAs in two isogenic diploid cell lines, one producing and one not producing the antitumor protein p53. We identified sites naturally modified only partially (confirming the existence in cells of compositionally distinct ribosomes with potentially specialized functions) and sites whose 2′-O-methylation is sensitive to p53. We mapped sites particularly vulnerable to a reduced level of the methyltransferase fibrillarin. The remarkable fact that these are largely sites of natural hypomodification provides initial insights into the mechanism of partial RNA modification. Sites where methylation appeared vulnerable lie peripherally on the 3-D structure of the ribosomal subunits, whereas the numerous modifications present at the core of the subunits, where the functional centers lie, appeared robustly made. We suggest that vulnerable sites of 2′-O-methylation are highly likely to undergo specific regulation during normal and pathological processes.
Reduced basal forebrain atrophy progression in a randomized Donepezil trial in prodromal Alzheimer’s disease
Authors: Cavedo Enrica , Grothe Michel J. , Colliot Olivier , Lista Simone , Chupin Marie , Dormont Didier , Houot Marion , Lehéricy Stephane , Teipel Stefan , Dubois Bruno , Hampel Harald ,   Hippocampus Study Group, Croisile Bernard , Louis Tisserand Guy , Bonafe Alain , Ousset Pierre J , Rouaud Olivier , Ricolfi Fréderic , Vighetto Alain , Pasquier Florence , Delmaire Christine , Ceccaldi Mathieu , Girard Nadine , Duveau Françoise , Sarazin Marie
Published: September 2017

Acetylcholinesterase inhibitors are approved drugs currently used for the treatment of Alzheimer’s disease (AD) dementia. Basal forebrain cholinergic system (BFCS) atrophy is reported to precede both entorhinal cortex atrophy and memory impairment in AD, challenging the traditional model of the temporal sequence of topographical pathology associated with AD. We studied the effect of one-year Donepezil treatment on the rate of BFCS atrophy in prodromal AD patients using a double-blind, randomized, placebo-controlled trial of Donepezil (10 mg/day). Reduced annual BFCS rates of atrophy were found in the Donepezil group compared to the Placebo treated arm. Secondary analyses on BFCS subregions demonstrated the largest treatment effects in the Nucleus Basalis of Meynert (NbM) and the medial septum/diagonal band (Ch1/2). Donepezil administered at a prodromal stage of AD seems to substantially reduce the rate of atrophy of the BFCS nuclei with highest concentration of cholinergic neurons projecting to the cortex (NbM), hippocampus and entorhinal cortex (Ch1/2).
Statistical Modeling of the Default Mode Brain Network Reveals a Segregated Highway Structure
Authors: Stillman Paul E. , Wilson James D. , Denny Matthew J. , Desmarais Bruce A. , Bhamidi Shankar , Cranmer Skyler J. , Lu Zhong-Lin
Published: September 2017

We investigate the functional organization of the Default Mode Network (DMN) – an important subnetwork within the brain associated with a wide range of higher-order cognitive functions. While past work has shown the whole-brain network of functional connectivity follows small-world organizational principles, subnetwork structure is less well understood. Current statistical tools, however, are not suited to quantifying the operating characteristics of functional networks as they often require threshold censoring of information and do not allow for inferential testing of the role that local processes play in determining network structure. Here, we develop the correlation Generalized Exponential Random Graph Model (cGERGM) – a statistical network model that uses local processes to capture the emergent structural properties of correlation networks without loss of information. Examining the DMN with the cGERGM, we show that, rather than demonstrating small-world properties, the DMN appears to be organized according to principles of a segregated highway – suggesting it is optimized for function-specific coordination between brain regions as opposed to information integration across the DMN. We further validate our findings through assessing the power and accuracy of the cGERGM on a testbed of simulated networks representing various commonly observed brain architectures.
The sensitivity of a radical pair compass magnetoreceptor can be significantly amplified by radical scavengers
Authors: Kattnig Daniel R. , Hore P. J.
Published: September 2017

Birds have a remarkable ability to obtain navigational information from the Earth’s magnetic field. The primary detection mechanism of this compass sense is uncertain but appears to involve the quantum spin dynamics of radical pairs formed transiently in cryptochrome proteins. We propose here a new version of the current model in which spin-selective recombination of the radical pair is not essential. One of the two radicals is imagined to react with a paramagnetic scavenger via spin-selective electron transfer. By means of simulations of the spin dynamics of cryptochrome-inspired radical pairs, we show that the new scheme offers two clear and important benefits. The sensitivity to a 50 μT magnetic field is greatly enhanced and, unlike the current model, the radicals can be more than 2 nm apart in the magnetoreceptor protein. The latter means that animal cryptochromes that have a tetrad (rather than a triad) of tryptophan electron donors can still be expected to be viable as magnetic compass sensors. Lifting the restriction on the rate of the spin-selective recombination reaction also means that the detrimental effects of inter-radical exchange and dipolar interactions can be minimised by placing the radicals much further apart than in the current model.