bluuebunny/crossref_metadata_2025 huggingface dataset:
On the swirling Trkalian mean flow field in solid rocket motors
Authors: Fist Andrew , Majdalani Joseph
Published: July 2017

In this work, an exact Euler solution is derived under the fundamental contingencies of axisymmetric, steady, rotational, incompressible, single-phase, non-reactive and inviscid fluid, which also stand behind the ubiquitously used mean flow profile named ‘Taylor–Culick.’ In comparison with the latter, which proves to be complex lamellar, the present model is derived in the context of a Trkalian flow field, and hence is capable of generating a non-zero swirl component that increases linearly in the streamwise direction. This enables us to provide an essential mathematical representation that is appropriate for flow configurations where the bulk gaseous motion is driven to swirl. From a procedural standpoint, the new Trkalian solution is deduced directly from the Bragg–Hawthorne equation, which has been repeatedly shown to possess sufficient latitude to reproduce several existing profiles such as Taylor–Culick’s as special cases. Throughout this study, the fundamental properties of the present model are considered and discussed in the light of existing flow approximations. Consistent with the original Taylor–Culick mean flow motion, the Trkalian velocity is seen to exhibit both axial and tangential components that increase linearly with the distance from the headwall, and a radial component that remains axially invariant. Furthermore, the Trkalian model is shown to form a subset of the Beltramian class of solutions for which the velocity and vorticity vectors are not only parallel but also directly proportional. This characteristic feature is interesting, as it stands in sharp contrast to the complex-lamellar nature of the Taylor–Culick motion, where the velocity and vorticity vectors remain orthogonal. By way of verification, a numerical simulation is carried out using a finite-volume solver, thus leading to a favourable agreement between theoretical and numerical predictions.
Not Just How Much You Know: Interactional Effect of Cultural Knowledge and Metacognition on Creativity in a Global Context—ADDENDUM
Authors: Chua Roy Y. J. , Ng Kok Yee
Published: July 2017

In view of MOR's recent changes to editorial policies (Lewin et al., 2016), this addendum is created to provide greater data transparency and richer discussions of our findings and their implications.
Management and Organization Review Special Issue ‘The Innovation and Entrepreneurship Ecosystem in India’
Authors: Bhagavatula Suresh , Mudambi Ram , Murmann Johann Peter
Published: July 2017

This Management of Organization Review (MOR) special issue aims to explore the key features of the innovation and entrepreneurship ecosystem in India. There is recent evidence that innovation and entrepreneurship dynamics in transforming economies differ from like processes in advanced market economies in significant ways (e.g., Maimone, Mudambi, Navarra, & Baglieri, 2016). Therefore, applying the dominant theoretical lens developed to study innovation and entrepreneurship in advanced market economies may be inappropriate. For instance, the Global Entrepreneurship Monitor (GEM) surveys clearly demonstrate the composition of total entrepreneurial activity (TEA) for advanced and transforming economies is substantially different, with a significantly higher level of ‘need-based’ entrepreneurship in the latter. Hence the typical advanced economy transition from wage employment to a larger share for entrepreneurship may be reversed in transforming economies. Transforming economies also witness a significant role of the transnational diaspora in their entrepreneurial and innovation processes (Riddle, Hrivnak, & Nielsen, 2010). Further, at the level of corporate entrepreneurship, London and Hart (2004) argue that results of studies of subsidiary entrepreneurship undertaken in advanced market economies may not generalize to transforming market economies. In summary, a fundamental question is whether entrepreneurship and innovation in transforming economies are diverging from the norms of advanced economies as these countries get wealthier and develop entirely new trajectories (Hill & Mudambi, 2010).
On the Meaning of “God”: Transcendence without Mythology
Authors: Kaufman Gordon D.
Published: July 2017

Many have observed that modern man, more than the man of any other age, lives in a world from which God is absent, a genuinely secular world. Our forefathers had a sense of God's continuous providential guidance of history as a whole and of their individual destinies in particular; they found their lives meaningful because they were lived within the context of God's purposes, each man having his own unique place and task. But such meaning as most men of our time find is the this-worldly humanly-created meaning emergent from ordinary social intercourse and/or cultural activity. For some this loss of a transcendent source and purpose has reduced human life to meaning-lessness and absurdity, a pointless and empty burden simply to be endured (Beckett); others react with bitterness and revulsion (Sartre); still others seem to find sufficient satisfaction in their daily round of activities, punctuated occasionally by aesthetic experience or unusual excitement, not to miss or lament the dimensions of depth and transcendence and mystery in which previous generations found their lives ensconced. But in any case the radical “eclipse of God” (Buber) or even the final irretrievable “death of God” (Nietzsche) appears to be the most momentous theological fact of our age. Given this cultural context, it is little wonder that linguistic analysts find it dubious whether the word “God” has any genuinely specifiable meaning, and theological writers, in a desperate attempt to rescue the Christian faith from what appears to be its certain demise, seek wholly “secular” interpretations which go so far as to dispense with the word and idea of “God” entirely.
Estimating age-time-dependent malaria force of infection accounting for unobserved heterogeneity
Authors: MUGENYI L. , ABRAMS S. , HENS N.
Published: July 2017

Despite well-recognized heterogeneity in malaria transmission, key parameters such as the force of infection (FOI) are generally estimated ignoring the intrinsic variability in individual infection risks. Given the potential impact of heterogeneity on the estimation of the FOI, we estimate this quantity accounting for both observed and unobserved heterogeneity. We used cohort data of children aged 0·5–10 years evaluated for the presence of malaria parasites at three sites in Uganda. Assuming a Susceptible–Infected–Susceptible model, we show how the FOI relates to the point prevalence, enabling the estimation of the FOI by modelling the prevalence using a generalized linear mixed model. We derive bounds for varying parasite clearance distributions. The resulting FOI varies significantly with age and is estimated to be highest among children aged 5–10 years in areas of high and medium malaria transmission and highest in children aged below 1 year in a low transmission setting. Heterogeneity is greater between than within households and it increases with decreasing risk of malaria infection. This suggests that next to the individual's age, heterogeneity in malaria FOI may be attributed to household conditions. When estimating the FOI, accounting for both observed and unobserved heterogeneity in malaria acquisition is important for refining malaria spread models.
The real or the Real? Chardin or Rothko?
Authors: O'Hear Anthony
Published: July 2017

I will begin by considering some themes from Proust's wonderful essay on Chardin, Chardin and Rembrandt (Proust, 1988). Proust speaks of the young man ‘of modest means and artistic taste’, his imagination filled with the splendour of museums, of cathedrals, of mountains, of the sea, sitting at table at the end of lunch, nauseated at the ‘traditional mundanity’ of the unaesthetic spectacle before him: the last knife left lying on the half turned-back table cloth, next to the remains of an underdone and tasteless cutlet. He cannot wait to get up and leave, and if he cannot take a train to Holland or Italy, he will at least go to the Louvre to have sight of the palaces of Veronese, the princes of van Dyck and the harbours of Claude. Doing this will, of course, make his return to his home and its familiar surroundings seem yet more drab and exasperating.
Consumption of ultra-processed foods and body fat during childhood and adolescence: a systematic review
Authors: Costa Caroline Santos , Del-Ponte Bianca , Assunção Maria Cecília Formoso , Santos Iná Silva
Published: July 2017

Objective

To review the available literature on the association between consumption of ultra-processed foods and body fat during childhood and adolescence.

Design

A systematic review was conducted in the PubMed, Web of Science and LILACS databases. Studies that evaluated the association between consumption of ultra-processed food (exposure) and body fat (outcome) during childhood and adolescence were eligible.

Subjects

Healthy children and adolescents.

Results

Twenty-six studies that evaluated groups of ultra-processed foods (such as snacks, fast foods, junk foods and convenience foods) or specific ultra-processed foods (soft drinks/sweetened beverages, sweets, chocolate and ready-to-eat cereals) were selected. Most of the studies (n15) had a cohort design. Consumption was generally evaluated by means of FFQ or food records; and body composition, by means of double indirect methods (bioelectrical impedance analysis and skinfolds). Most of the studies that evaluated consumption of groups of ultra-processed foods and soft drinks/sweetened beverages found positive associations with body fat.

Conclusions

Our review showed that most studies have found positive associations between consumption of ultra-processed food and body fat during childhood and adolescence. There is a need to use a standardized classification that considers the level of food processing to promote comparability between studies.
CME: Früherkennung Brustkrebs – Stellenwert der Screening-Mammografie anhand eines Fallbeispiels
Authors: Seifert Heike , Siebenhüner Alexander
Published: July 2017

Zusammenfassung. Zusammenfassung: Das Mammakarzinom ist die häufigste Tumorerkrankung der Frau und immer noch die häufigste tumorbedingte Todesursache. Strukturierte Früherkennungsuntersuchungen sollen die Krebsmortalität senken. Die Karzinomvorsorge der Frau, insbesondere ausgerichtet auf den Brustkrebs, ist in der Schweiz auf kantonaler Ebene und bis anhin nicht flächendeckend reguliert. In den internationalen Guidelines (S3, ESMO, NCCN) ist eine Screening-Untersuchung mittels Mammografie alle zwei Jahre (während zwanzig Jahren) in der Altersgruppe 50–69 Jahre empfohlen. Einige internationale Studien wiesen eine relative Reduktion der Gesamtmortalität von 25–45 % durch das Screening und durch eine Behandlung von Brustkrebs im Frühstadium auf. Das folgende CME gibt einen Überblick über den aktuellen Stand des Mammografie-Screenings und diskutiert Vor- und Nachteile von möglichen diagnostischen und therapeutischen Schritten.
Enhancing a slow and weak optomechanical nonlinearity with delayed quantum feedback
Authors: Wang Zhaoyou , Safavi-Naeini Amir H.
Published: July 2017

A central goal of quantum optics is to generate large interactions between single photons so that one photon can strongly modify the state of another one. In cavity optomechanics, photons interact with the motional degrees of freedom of an optical resonator, for example, by imparting radiation pressure forces on a movable mirror or sensing minute fluctuations in the position of the mirror. Here, we show that the optical nonlinearity arising from these effects, typically too small to operate on single photons, can be sufficiently enhanced with feedback to generate large interactions between single photons. We propose a protocol that allows photons propagating in a waveguide to interact with each other through multiple bounces off an optomechanical system. The protocol is analysed by evolving the full many-body quantum state of the waveguide-coupled system, illustrating that large photon–photon interactions mediated by mechanical motion may be within experimental reach.
Marine viruses discovered via metagenomics shed light on viral strategies throughout the oceans
Authors: Coutinho Felipe H. , Silveira Cynthia B. , Gregoracci Gustavo B. , Thompson Cristiane C. , Edwards Robert A. , Brussaard Corina P. D. , Dutilh Bas E. , Thompson Fabiano L.
Published: July 2017

Marine viruses are key drivers of host diversity, population dynamics and biogeochemical cycling and contribute to the daily flux of billions of tons of organic matter. Despite recent advancements in metagenomics, much of their biodiversity remains uncharacterized. Here we report a data set of 27,346 marine virome contigs that includes 44 complete genomes. These outnumber all currently known phage genomes in marine habitats and include members of previously uncharacterized lineages. We designed a new method for host prediction based on co-occurrence associations that reveals these viruses infect dominant members of the marine microbiome such asProchlorococcusandPelagibacter. A negative association between host abundance and the virus-to-host ratio supports the recently proposed Piggyback-the-Winner model of reduced phage lysis at higher host densities. An analysis of the abundance patterns of viruses throughout the oceans revealed how marine viral communities adapt to various seasonal, temperature and photic regimes according to targeted hosts and the diversity of auxiliary metabolic genes.
Giant linear strain gradient with extremely low elastic energy in a perovskite nanostructure array
Authors: Tang Y. L. , Zhu Y. L. , Liu Y. , Wang Y. J. , Ma X. L.
Published: July 2017

Although elastic strains, particularly inhomogeneous strains, are able to tune, enhance or create novel properties of some nanoscale functional materials, potential devices dominated by inhomogeneous strains have not been achieved so far. Here we report a fabrication of inhomogeneous strains with a linear gradient as giant as 106 per metre, featuring an extremely lower elastic energy cost compared with a uniformly strained state. The present strain gradient, resulting from the disclinations in the BiFeO3 nanostructures array grown on LaAlO3 substrates via a high deposition flux, induces a polarization of several microcoulomb per square centimetre. It leads to a large built-in electric field of several megavoltage per metre, and gives rise to a large enhancement of solar absorption. Our results indicate that it is possible to build up large-scale strain-dominated nanostructures with exotic properties, which in turn could be useful in the development of novel devices for electromechanical and photoelectric applications.
SRSF1-dependent nuclear export inhibition of C9ORF72 repeat transcripts prevents neurodegeneration and associated motor deficits
Authors: Hautbergue Guillaume M. , Castelli Lydia M. , Ferraiuolo Laura , Sanchez-Martinez Alvaro , Cooper-Knock Johnathan , Higginbottom Adrian , Lin Ya-Hui , Bauer Claudia S. , Dodd Jennifer E. , Myszczynska Monika A. , Alam Sarah M. , Garneret Pierre , Chandran Jayanth S. , Karyka Evangelia , Stopford Matthew J. , Smith Emma F. , Kirby Janine , Meyer Kathrin , Kaspar Brian K. , Isaacs Adrian M. , El-Khamisy Sherif F. , De Vos Kurt J. , Ning Ke , Azzouz Mimoun , Whitworth Alexander J. , Shaw Pamela J.
Published: July 2017

Hexanucleotide repeat expansions in theC9ORF72gene are the commonest known genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia. Expression of repeat transcripts and dipeptide repeat proteins trigger multiple mechanisms of neurotoxicity. How repeat transcripts get exported from the nucleus is unknown. Here, we show that depletion of the nuclear export adaptor SRSF1 prevents neurodegeneration and locomotor deficits in aDrosophilamodel of C9ORF72-related disease. This intervention suppresses cell death of patient-derived motor neuron and astrocytic-mediated neurotoxicity in co-culture assays. We further demonstrate that either depleting SRSF1 or preventing its interaction with NXF1 specifically inhibits the nuclear export of pathologicalC9ORF72transcripts, the production of dipeptide-repeat proteins and alleviates neurotoxicity inDrosophila, patient-derived neurons and neuronal cell models. Taken together, we show that repeat RNA-sequestration of SRSF1 triggers the NXF1-dependent nuclear export ofC9ORF72transcripts retaining expanded hexanucleotide repeats and reveal a novel promising therapeutic target for neuroprotection.
CTCF orchestrates the germinal centre transcriptional program and prevents premature plasma cell differentiation
Authors: Pérez-García Arantxa , Marina-Zárate Ester , Álvarez-Prado Ángel F. , Ligos Jose M. , Galjart Niels , Ramiro Almudena R.
Published: July 2017

In germinal centres (GC) mature B cells undergo intense proliferation and immunoglobulin gene modification before they differentiate into memory B cells or long-lived plasma cells (PC). GC B-cell-to-PC transition involves a major transcriptional switch that promotes a halt in cell proliferation and the production of secreted immunoglobulins. Here we show that the CCCTC-binding factor (CTCF) is required for the GC reactionin vivo, whereasin vitrothe requirement for CTCF is not universal and instead depends on the pathways used for B-cell activation. CTCF maintains the GC transcriptional programme, allows a high proliferation rate, and represses the expression of Blimp-1, the master regulator of PC differentiation. Restoration of Blimp-1 levels partially rescues the proliferation defect of CTCF-deficient B cells. Thus, our data reveal an essential function of CTCF in maintaining the GC transcriptional programme and preventing premature PC differentiation.
Electrical gate control of spin current in van der Waals heterostructures at room temperature
Authors: Dankert André , Dash Saroj P.
Published: July 2017

Two-dimensional (2D) crystals offer a unique platform due to their remarkable and contrasting spintronic properties, such as weak spin–orbit coupling (SOC) in graphene and strong SOC in molybdenum disulfide (MoS2). Here we combine graphene and MoS2 in a van der Waals heterostructure (vdWh) to demonstrate the electric gate control of the spin current and spin lifetime at room temperature. By performing non-local spin valve and Hanle measurements, we unambiguously prove the gate tunability of the spin current and spin lifetime in graphene/MoS2 vdWhs at 300 K. This unprecedented control over the spin parameters by orders of magnitude stems from the gate tuning of the Schottky barrier at the MoS2/graphene interface and MoS2 channel conductivity leading to spin dephasing in high-SOC material. Our findings demonstrate an all-electrical spintronic device at room temperature with the creation, transport and control of the spin in 2D materials heterostructures, which can be key building blocks in future device architectures.
Insight into microtubule disassembly by kinesin-13s from the structure of Kif2C bound to tubulin
Authors: Wang Weiyi , Cantos-Fernandes Soraya , Lv Yuncong , Kuerban Hureshitanmu , Ahmad Shoeb , Wang Chunguang , Gigant Benoît
Published: July 2017

Kinesin-13s are critical microtubule regulators which induce microtubule disassembly in an ATP dependent manner. To clarify their mechanism, we report here the crystal structure of a functional construct of the kinesin-13 Kif2C/MCAK in an ATP-like state and bound to the αβ-tubulin heterodimer, a complex mimicking the species that dissociates from microtubule ends during catalytic disassembly. Our results picture how Kif2C stabilizes a curved tubulin conformation. The Kif2C α4-L12-α5 region undergoes a remarkable 25° rotation upon tubulin binding to target the αβ-tubulin hinge. This movement leads the β5a–β5b motif to interact with the distal end of β-tubulin, whereas the neck and the KVD motif, two specific elements of kinesin-13s, target the α-tubulin distal end. Taken together with the study of Kif2C mutants, our data suggest that stabilization of a curved tubulin is an important contribution to the Kif2C mechanism.
Genistein Protects Genioglossus Myoblast Against Hypoxia-induced Injury through PI3K-Akt and ERK MAPK Pathways
Authors: Ding Wanghui , Chen Xiaoyan , Li Wen , Fu Zhen , Shi Jiejun
Published: July 2017

Obstructive sleep apnea and hypopnea syndrome (OSAHS) is a clinical syndrome characterized by recurrent episodes of obstruction of the upper airway during sleep that leads to a hypoxic condition. Genioglossus, an important pharyngeal muscle, plays an important role in maintaining an open upper airway for effective breathing. Our previous study found that genistein (a kind of phytoestrogen) protects genioglossus muscle from hypoxia-induced oxidative injury. However, the underlying mechanism is still unknown. In the present study, we examined the effects of hypoxia on genioglossus myoblast proliferation, viability and apoptosis, and the protective effect of genistein and its relationship with the PI3K/Akt and ERK MAPK pathways. Cell viability and Bcl-2 were reduced under hypoxic condition, while ROS generation, caspase-3, MDA, and DNA damage were increased following a hypoxia exposure. However, the effects of hypoxia were partially reversed by genistein in an Akt- and ERK- (but not estrogen receptor) dependent manner. In conclusion, genistein protects genioglossus myoblasts against hypoxia-induced oxidative injury and apoptosis independent of estrogen receptor. The PI3K-Akt and ERK1/2 MAPK signaling pathways are involved in the antioxidant and anti-apoptosis effect of genistein on genioglossus myoblasts.
Integrating nonstationary behaviors of typhoon and non-typhoon extreme rainfall events in East Asia
Authors: Son Chanyoung , Lee Taesam , Kwon Hyun-han
Published: July 2017

Extreme rainfall events in East Asia can be derived from the two subcomponents of tropical cyclones (TC) and non-TC based rainfall (mostly summer monsoons). Critical natural hazards including floods and landslides occur repeatedly due to the heavy rainfall associated with the two subcomponents, and disaster losses are increasing because global warming has caused changes in the extreme rainfall characteristics of two subcomponents. Subsequently, the frequency and intensity of extreme rainfall have reportedly become nonstationary. The majority of literature on nonstationary frequency analyses do not account for the different behaviors (stationarity or nonstationarity) of annual maximum rainfall (AMR) from the two subcomponents (PM
TC
and PM
NTC
). To carry out a nonstationary frequency analysis considering the different behaviors of the PM
TC
and PM
NTC
series, this study proposes a novel approach of integrating the fitted PM
TC
and PM
NTC
series after modeling the nonstationarity of the PM
TC
and PM
NTC
series individually. The presented results conclude that the proposed approach provides more reliable estimates than existing nonstationary approaches by reflecting the different features of the PM
TC
and PM
NTC
series. We suggest that the proposed approach provides a reasonable design rainfall in constructing hydraulics to mitigate the different nonstationary effects of two TC and non-TC rainfall extremes.
Ectodysplasin target gene Fgf20 regulates mammary bud growth and ductal invasion and branching during puberty
Authors: Elo Teresa , Lindfors Päivi H. , Lan Qiang , Voutilainen Maria , Trela Ewelina , Ohlsson Claes , Huh Sung-Ho , Ornitz David M. , Poutanen Matti , Howard Beatrice A. , Mikkola Marja L.
Published: July 2017

Mammary gland development begins with the appearance of epithelial placodes that invaginate, sprout, and branch to form small arborized trees by birth. The second phase of ductal growth and branching is driven by the highly invasive structures called terminal end buds (TEBs) that form at ductal tips at the onset of puberty. Ectodysplasin (Eda), a tumor necrosis factor-like ligand, is essential for the development of skin appendages including the breast. In mice, Eda regulates mammary placode formation and branching morphogenesis, but the underlying molecular mechanisms are poorly understood. Fibroblast growth factor (Fgf) receptors have a recognized role in mammary ductal development and stem cell maintenance, but the ligands involved are ill-defined. Here we report that Fgf20 is expressed in embryonic mammary glands and is regulated by the Eda pathway. Fgf20 deficiency does not impede mammary gland induction, but compromises mammary bud growth, as well as TEB formation, ductal outgrowth and branching during puberty. We further show that loss of Fgf20 delays formation of Eda-induced supernumerary mammary buds and normalizes the embryonic and postnatal hyperbranching phenotype of Eda overexpressing mice. These findings identify a hitherto unknown function for Fgf20 in mammary budding and branching morphogenesis.
A Transcription Activator-Like Effector Tal7 of Xanthomonas oryzae pv. oryzicola Activates Rice Gene Os09g29100 to Suppress Rice Immunity
Authors: Cai Lulu , Cao Yanyan , Xu Zhengyin , Ma Wenxiu , Zakria Muhammad , Zou Lifang , Cheng Zaiquan , Chen Gongyou
Published: July 2017

Xanthomonas oryzaepv.oryzicola(Xoc) andX.oryzaepv.oryzae(Xoo) cause bacterial leaf streak (BLS) and bacterial leaf blight (BLB) in rice, respectively. UnlikeXoo, endogenous avirulence-resistance (avr-R) gene interactions have not been identified in theXoc-rice pathosystem; however, both pathogens possess transcription activator-like effectors (TALEs) that are known to modulateRorSgenes in rice. The transfer of individualtalgenes fromXocRS105 (hypervirulent) intoXocYNB0-17 (hypovirulent) led to the identification oftal7, which suppressedavrXa7-Xa7mediated defense in rice containing anXa7 Rgene. Mobility shift and microscale thermophoresis assays showed that Tal7 bound two EBE sites in the promoters of two rice genes,Os09g29100andOs12g42970, which encode predicted Cyclin-D4-1 and GATA zinc finger family protein, respectively. Assays using designer TALEs and a TALE-free strain ofXoorevealed thatOs09g29100was the biologically relevant target of Tal7. Tal7 activates the expression of rice geneOs09g29100that suppressesavrXa7-Xa7mediated defense in Rice. TALEN editing of the Tal7-binding site in theOs09g29100gene promoter further enhanced resistance to the pathogenXocRS105. The suppression of effector-trigger immunity (ETI) is a phenomenon that may contribute to the scarcity of BLS resistant cultivars.
Injectable hybrid system for strontium local delivery promotes bone regeneration in a rat critical-sized defect model
Authors: Henriques Lourenço Ana , Neves Nuno , Ribeiro-Machado Cláudia , Sousa Susana R. , Lamghari Meriem , Barrias Cristina C. , Trigo Cabral Abel , Barbosa Mário A. , Ribeiro Cristina C.
Published: July 2017

Strontium (Sr) has been described as having beneficial influence in bone strength and architecture. However, negative systemic effects have been reported on oral administration of Sr ranelate, leading to strict restrictions in clinical application. We hypothesized that local delivery of Sr improves osteogenesis without eliciting detrimental side effects. Therefore, the in vivo response to an injectable Sr-hybrid system composed of RGD-alginate hydrogel cross-linked in situ with Sr and reinforced with Sr-doped hydroxyapatite microspheres, was investigated. The system was injected in a critical-sized bone defect model and compared to a similar Sr-free material. Micro-CT results show a trend towards higher new bone formed in Sr-hybrid group and major histological differences were observed between groups. Higher cell invasion was detected at the center of the defect of Sr-hybrid group after 15 days with earlier bone formation. Higher material degradation with increase of collagen fibers and bone formation in the center of the defect after 60 days was observed as opposed to bone formation restricted to the periphery of the defect in the control. These histological findings support the evidence of an improved response with the Sr enriched material. Importantly, no alterations were observed in the Sr levels in systemic organs or serum.
Characterizing the scent and chemical composition of Panthera leo marking fluid using solid-phase microextraction and multidimensional gas chromatography–mass spectrometry-olfactometry
Authors: Soso Simone B. , Koziel Jacek A.
Published: July 2017

Lions (Panthera leo) use chemical signaling to indicate health, reproductive status, and territorial ownership. To date, no study has reported on both scent and composition of marking fluid (MF) fromP. leo. The objectives of this study were to: 1) develop a novel method for simultaneous chemical and scent identification of lion MF in its totality (urine + MF), 2) identify characteristic odorants responsible for the overall scent of MF as perceived by human panelists, and 3) compare the existing library of known odorous compounds characterized as eliciting behaviors in animals in order to understand potential functionality in lion behavior. Solid-phase microextraction and simultaneous chemical-sensory analyses with multidimensional gas-chromatography-mass spectrometry-olfactometry improved separating, isolating, and identifying mixed (MF, urine) compounds versus solvent-based extraction and chemical analyses. 2,5-Dimethylpyrazine, 4-methylphenol, and 3-methylcyclopentanone were isolated and identified as the compounds responsible for the characteristic odor of lion MF. Twenty-eight volatile organic compounds (VOCs) emitted from MF were identified, adding a new list of compounds previously unidentified in lion urine. New chemicals were identified in nine compound groups: ketones, aldehydes, amines, alcohols, aromatics, sulfur-containing compounds, phenyls, phenols, and volatile fatty acids. Twenty-three VOCs are known semiochemicals that are implicated in attraction, reproduction, and alarm-signaling behaviors in other species.
The energy disruptor metformin targets mitochondrial integrity via modification of calcium flux in cancer cells
Authors: Loubiere Camille , Clavel Stephan , Gilleron Jerome , Harisseh Rania , Fauconnier Jeremy , Ben-Sahra Issam , Kaminski Lisa , Laurent Kathiane , Herkenne Stephanie , Lacas-Gervais Sandra , Ambrosetti Damien , Alcor Damien , Rocchi Stephane , Cormont Mireille , Michiels Jean-François , Mari Bernard , Mazure Nathalie M. , Scorrano Luca , Lacampagne Alain , Gharib Abdallah , Tanti Jean-François , Bost Frederic
Published: July 2017

Mitochondrial integrity is critical for the regulation of cellular energy and apoptosis. Metformin is an energy disruptor targeting complex I of the respiratory chain. We demonstrate that metformin induces endoplasmic reticulum (ER) stress, calcium release from the ER and subsequent uptake of calcium into the mitochondria, thus leading to mitochondrial swelling. Metformin triggers the disorganization of the cristae and inner mitochondrial membrane in several cancer cells and tumors. Mechanistically, these alterations were found to be due to calcium entry into the mitochondria, because the swelling induced by metformin was reversed by the inhibition of mitochondrial calcium uniporter (MCU). We also demonstrated that metformin inhibits the opening of mPTP and induces mitochondrial biogenesis. Altogether, the inhibition of mPTP and the increase in mitochondrial biogenesis may account for the poor pro-apoptotic effect of metformin in cancer cells.
Honeybee (Apis mellifera)-associated bacterial community affected by American foulbrood: detection of Paenibacillus larvae via microbiome analysis
Authors: Erban Tomas , Ledvinka Ondrej , Kamler Martin , Nesvorna Marta , Hortova Bronislava , Tyl Jan , Titera Dalibor , Markovic Martin , Hubert Jan
Published: July 2017

Honeybee (Apis mellifera L.) workers act as passive vectors of Paenibacillus larvae spores, which cause the quarantine disease American foulbrood (AFB). We assessed the relative proportions of P. larvae within the honeybee microbiome using metabarcoding analysis of the 16 S rRNA gene. The microbiome was analyzed in workers outside of the AFB zone (control - AFB0), in workers from asymptomatic colonies in an AFB apiary (AFB1), and in workers from colonies exhibiting clinical AFB symptoms (AFB2). The microbiome was processed for the entire community and for a cut-off microbiome comprising pathogenic/environmental bacteria following the removal of core bacterial sequences; varroosis levels were considered in the statistical analysis. No correlation was observed between AFB status and varroosis level, but AFB influenced the worker bee bacterial community, primarily the pathogenic/environmental bacteria. There was no significant difference in the relative abundance of P. larvae between the AFB1 and AFB0 colonies, but we did observe a 9-fold increase in P. larvae abundance in AFB2 relative to the abundance in AFB1. The relative sequence numbers of Citrobacter freundii and Hafnia alvei were higher in AFB2 and AFB1 than in AFB0, whereas Enterococcus faecalis, Klebsiella oxytoca, Spiroplasma melliferum and Morganella morganii were more abundant in AFB0 and AFB1 than in AFB2.
A Tissue Engineered Model of Aging: Interdependence and Cooperative Effects in Failing Tissues
Authors: Acun A. , Vural D. C. , Zorlutuna P.
Published: July 2017

Aging remains a fundamental open problem in modern biology. Although there exist a number of theories on aging on the cellular scale, nearly nothing is known about how microscopic failures cascade to macroscopic failures of tissues, organs and ultimately the organism. The goal of this work is to bridge microscopic cell failure to macroscopic manifestations of aging. We use tissue engineered constructs to control the cellular-level damage and cell-cell distance in individual tissues to establish the role of complex interdependence and interactions between cells in aging tissues. We found that while microscopic mechanisms drive aging, the interdependency between cells plays a major role in tissue death, providing evidence on how cellular aging is connected to its higher systemic consequences.
Human Platelet Lysate versus Fetal Calf Serum: These Supplements Do Not Select for Different Mesenchymal Stromal Cells
Authors: Fernandez-Rebollo Eduardo , Mentrup Birgit , Ebert Regina , Franzen Julia , Abagnale Giulio , Sieben Torsten , Ostrowska Alina , Hoffmann Per , Roux Pierre-François , Rath Björn , Goodhardt Michele , Lemaitre Jean-Marc , Bischof Oliver , Jakob Franz , Wagner Wolfgang
Published: July 2017

Culture medium of mesenchymal stromal cells (MSCs) is usually supplemented with either human platelet lysate (HPL) or fetal calf serum (FCS). Many studies have demonstrated that proliferation and cellular morphology are affected by these supplements – it is therefore important to determine if they favor outgrowth of different subpopulations and thereby impact on the heterogeneous composition of MSCs. We have isolated and expanded human bone marrow-derived MSCs in parallel with HPL or FCS and demonstrated that HPL significantly increases proliferation and leads to dramatic differences in cellular morphology. Remarkably, global DNA-methylation profiles did not reveal any significant differences. Even at the transcriptomic level, there were only moderate changes in pairwise comparison. Furthermore, the effects on proliferation, cytoskeletal organization, and focal adhesions were reversible by interchanging to opposite culture conditions. These results indicate that cultivation of MSCs with HPL or FCS has no systematic bias for specific cell types.
Effects of sediment smothering on the sponge holobiont with implications for dredging management
Authors: Pineda Mari-Carmen , Strehlow Brian , Sternel Miriam , Duckworth Alan , Haan Joost den , Jones Ross , Webster Nicole S.
Published: July 2017

One of the ways dredging can affect benthic habitats is through high levels of sediment deposition, which has the potential to smother sessile organisms such as sponges. In order to provide pressure-response values to sedimentation and tease apart the different cause-effect pathways of high turbidity, 5 sponge species, including heterotrophic and phototrophic nutritional modes, were exposed for up to 30 d to multiple sediment deposition events, each of which resulted in an initial covering of 80–100% of the surface of the sponges in a layer ~0.5 mm thick. The response of the sponges was examined using a suite of different response variables including growth, respiration, lipid content, community composition of the microbial symbionts, and maximum quantum yield and chlorophyll content of the phototrophic symbionts. Different species showed different mechanisms of sediment rejection and different patterns of sediment clearance. All species survived the treatments, were able to tolerate high levels of partial covering of their surfaces, and for most species the treatment did not alter the health of the sponge holobiont. Results from this study will guide interpretation of experiments examining the combined effects of all three dredging-related pressures, and aid the development of water quality thresholds for impact prediction purposes.
Effects of combined dredging-related stressors on sponges: a laboratory approach using realistic scenarios
Authors: Pineda Mari-Carmen , Strehlow Brian , Kamp Jasmine , Duckworth Alan , Jones Ross , Webster Nicole S.
Published: July 2017

Dredging can cause increased suspended sediment concentrations (SSCs), light attenuation and sedimentation in marine communities. In order to determine the combined effects of dredging-related pressures on adult sponges, three species spanning different nutritional modes and morphologies were exposed to 5 treatment levels representing realistic dredging scenarios. Most sponges survived under low to moderate turbidity scenarios (SSCs of ≤ 33 mg L−1, and a daily light integral of ≥0.5 mol photons m−2 d−1) for up to 28 d. However, under the highest turbidity scenario (76 mg L−1, 0.1 mol photons m−2 d−1) there was 20% and 90% mortality of the phototrophic sponges Cliona orientalis and Carteriospongia foliascens respectively, and tissue regression in the heterotrophic Ianthella basta. All three sponge species exhibited mechanisms to effectively tolerate dredging-related pressures in the short term (e.g. oscula closure, mucus production and tissue regression), although reduced lipids and deterioration of sponge health suggest that longer term exposure to similar conditions is likely to result in higher mortality. These results suggest that the combination of high SSCs and low light availability can accelerate mortality, increasing the probability of biological effects, although there is considerable interspecies variability in how adult sponges respond to dredging pressures.
Detecting the presence of fish farm-derived organic matter at the seafloor using stable isotope analysis of phospholipid fatty acids
Authors: Mayor Daniel J. , Gray Nia B. , Hattich Giannina S. I. , Thornton Barry
Published: July 2017

The expansion of global aquaculture activities is important for the wellbeing of future generations in terms of employment and food security. Rearing animals in open-exchange cages permits the release of organic wastes, some of which ultimately reaches the underlying sediments. The development of rapid, quantitative and objective monitoring techniques is therefore central to the environmentally sustainable growth of the aquaculture industry. Here, we demonstrate that fish farm-derived organic wastes can be readily detected at the seafloor by quantifying sediment phospholipid fatty acids (PLFAs) and their carbon stable isotope signatures. Observations across five farms reveal that farm size and/or distance away from it influence the spatial distribution of the generated organic wastes and their effect on benthic bacterial biomass. Comparison to the isotopic signatures of fish feed-derived PLFAs indicates that 16:0 and 18:1(n-9) are potential biomarkers for fish farm-derived organic wastes. Our results suggest that stable isotope analysis of sediment PLFAs has potential for monitoring the environmental performance of aquaculture activities, particularly given the increasing prevalence of terrigenous organic matter in aquaculture feed stocks because it is isotopically district to marine organic matter.
Complementary Role of Fibroblast Growth Factor 21 and Cytokeratin 18 in Monitoring the Different Stages of Nonalcoholic Fatty Liver Disease
Authors: Wu Guangyu , Li Huating , Fang Qichen , Zhang Jing , Zhang Mingliang , Zhang Lei , Wu Liang , Hou Xuhong , Lu Junxi , Bao Yuqian , Jia Weiping
Published: July 2017

Fibroblast growth factor 21 (FGF21) and cytokeratin 18 (CK18) were previously reported to be elevated in nonalcoholic fatty liver disease (NAFLD). We aim to analyze the differential roles of FGF21, cell apoptosis marker CK18 fragment M30 and total cell death marker CK18 M65ED in monitoring the different stages of NAFLD spectrum in a population-based prospective cohort comprising 808 Chinese subjects. Predictive performances for monitoring the different stages of NAFLD were assessed by logistic regression and receiver-operating characteristic (ROC) curves. We found baseline FGF21 but not CK18 level was an independent predictor for the development of simple steatosis. NAFLD patients who had remission during follow-up had significantly lower baseline M30 levels than those who sustained NAFLD (84.74U/L [53.26–135.79] vs. 118.47U/L [87.16–188.89], P = 0.012). M65ED was independently predictive of progressing to suspected non-alcoholic steatohepatitis (NASH) in NAFLD patients. These results suggest that FGF21 can be used for early identification of hepatic steatosis. On the other hand, CK18 including M30 and M65ED, are predictive of the prognosis of NAFLD patients. FGF21 and CK18 might play differential roles and have complementary value in non-invasive identification and monitoring the outcome of NAFLD patients.
Location Sensitive Deep Convolutional Neural Networks for Segmentation of White Matter Hyperintensities
Authors: Ghafoorian Mohsen , Karssemeijer Nico , Heskes Tom , van Uden Inge W. M. , Sanchez Clara I. , Litjens Geert , de Leeuw Frank-Erik , van Ginneken Bram , Marchiori Elena , Platel Bram
Published: July 2017

The anatomical location of imaging features is of crucial importance for accurate diagnosis in many medical tasks. Convolutional neural networks (CNN) have had huge successes in computer vision, but they lack the natural ability to incorporate the anatomical location in their decision making process, hindering success in some medical image analysis tasks. In this paper, to integrate the anatomical location information into the network, we propose several deep CNN architectures that consider multi-scale patches or take explicit location features while training. We apply and compare the proposed architectures for segmentation of white matter hyperintensities in brain MR images on a large dataset. As a result, we observe that the CNNs that incorporate location information substantially outperform a conventional segmentation method with handcrafted features as well as CNNs that do not integrate location information. On a test set of 50 scans, the best configuration of our networks obtained a Dice score of 0.792, compared to 0.805 for an independent human observer. Performance levels of the machine and the independent human observer were not statistically significantly different (p-value = 0.06).
αSynuclein control of mitochondrial homeostasis in human-derived neurons is disrupted by mutations associated with Parkinson’s disease
Authors: Pozo Devoto Victorio Martin , Dimopoulos Nicolas , Alloatti Matías , Pardi María Belén , Saez Trinidad M. , Otero María Gabriela , Cromberg Lucas Eneas , Marín-Burgin Antonia , Scassa Maria Elida , Stokin Gorazd B. , Schinder Alejandro F. , Sevlever Gustavo , Falzone Tomás Luis
Published: July 2017

The etiology of Parkinson’s disease (PD) converges on a common pathogenic pathway of mitochondrial defects in which α-Synuclein (αSyn) is thought to play a role. However, the mechanisms by which αSyn and its disease-associated allelic variants cause mitochondrial dysfunction remain unknown. Here, we analyzed mitochondrial axonal transport and morphology in human-derived neurons overexpressing wild-type (WT) αSyn or the mutated variants A30P or A53T, which are known to have differential lipid affinities. A53T αSyn was enriched in mitochondrial fractions, inducing significant mitochondrial transport defects and fragmentation, while milder defects were elicited by WT and A30P. We found that αSyn-mediated mitochondrial fragmentation was linked to expression levels in WT and A53T variants. Targeted delivery of WT and A53T αSyn to the outer mitochondrial membrane further increased fragmentation, whereas A30P did not. Genomic editing to disrupt the N-terminal domain of αSyn, which is important for membrane association, resulted in mitochondrial elongation without changes in fusion-fission protein levels, suggesting that αSyn plays a direct physiological role in mitochondrial size maintenance. Thus, we demonstrate that the association of αSyn with the mitochondria, which is modulated by protein mutation and dosage, influences mitochondrial transport and morphology, highlighting its relevance in a common pathway impaired in PD.
The Association between High Fat Diet around Gestation and Metabolic Syndrome-related Phenotypes in Rats: A Systematic Review and Meta-Analysis
Authors: Tellechea Mariana L. , Mensegue Melisa F. , Pirola Carlos J.
Published: July 2017

Numerous rodent studies have evaluated the effects of a maternal high-fat diet (HFD) on later in life susceptibility to Metabolic Syndrome (MetS) with varying results. Our aim was to quantitatively synthesize the available data on effects of maternal HFD around gestation on offspring’s body mass, body fat, plasma leptin, glucose, insulin, lipids and systolic blood pressure (SBP). Literature was screened and summary estimates of the effect of maternal HFD on outcomes were calculated by using fixed- or random-effects models. 362 effect sizes from 68 studies together with relevant moderators were collected. We found that maternal HFD is statistically associated with higher body fat, body weight, leptin, glucose, insulin and triglycerides levels, together with increased SBP in offspring later in life. Our analysis also revealed non-significant overall effect on offspring’s HDL-cholesterol. A main source of variation among studies emerged from rat strain and lard-based diet type. Strain and sex -specific effects on particular data subsets were detected. Recommendations are suggested for future research in the field of developmental programming of the MetS. Despite significant heterogeneity, our meta-analysis confirms that maternal HFD had long-term metabolic effects in offspring.