bluuebunny/crossref_metadata_2025_split huggingface dataset:
Combined inhibition of AKT/mTOR and MDM2 enhances Glioblastoma Multiforme cell apoptosis and differentiation of cancer stem cells
Authors: Daniele Simona , Costa Barbara , Zappelli Elisa , Da Pozzo Eleonora , Sestito Simona , Nesi Giulia , Campiglia Pietro , Marinelli Luciana , Novellino Ettore , Rapposelli Simona , Martini Claudia 
Published: April 2015

AbstractThe poor prognosis of Glioblastoma Multiforme (GBM) is due to a high resistance to conventional treatments and to the presence of a subpopulation of glioma stem cells (GSCs). Combination therapies targeting survival/self-renewal signals of GBM and GSCs are emerging as useful tools to improve GBM treatment. In this context, the hyperactivated AKT/mammalian target of the rapamycin (AKT/mTOR) and the inhibited wild-type p53 appear to be good candidates. Herein, the interaction between these pathways was investigated, using the novel AKT/mTOR inhibitor FC85 and ISA27, which re-activates p53 functionality by blocking its endogenous inhibitor murine double minute 2 homologue (MDM2). In GBM cells, FC85 efficiently inhibited AKT/mTOR signalling and reactivated p53 functionality, triggering cellular apoptosis. The combined therapy with ISA27 produced a synergic effect on the inhibition of cell viability and on the reactivation of p53 pathway. Most importantly, FC85 and ISA27 blocked proliferation and promoted the differentiation of GSCs. The simultaneous use of these compounds significantly enhanced GSC differentiation/apoptosis. These findings suggest that FC85 actively enhances the downstream p53 signalling and that a combination strategy aimed at inhibiting the AKT/mTOR pathway and re-activating p53 signalling is potentially effective in GBM and in GSCs.
The fossil record of phenotypic integration and modularity: A deep-time perspective on developmental and evolutionary dynamics
Authors: Goswami Anjali , Binder Wendy J. , Meachen Julie , O’Keefe F. Robin 
Published: April 2015

SignificanceVariation is the raw material for evolution, but studies have yet to unify the effects of intrinsic genetic and developmental interactions that influence variation with the extrinsic factors that shape organismal diversity on a large scale. Analysis of phenotypic integration can bridge different facets of evolutionary study and address fundamental questions on developmental and evolutionary dynamics through deep time. Our study of Late Pleistocene saber-toothed cats and dire wolves demonstrates that developmental integration channeled increasing amounts of morphological variation through 27,000 years of climate change, validating results from laboratory-based studies with the natural experiments captured in the fossil record.
Changing the picture of Earth's earliest fossils (3.5–1.9 Ga) with new approaches and new discoveries
Authors: Brasier Martin D. , Antcliffe Jonathan , Saunders Martin , Wacey David 
Published: April 2015

Significance
Precambrian fossils are essential for understanding the emergence of complex life. New analytical tools and new fossil discoveries are now changing the picture, allowing us to refine and extend our knowledge about the early fossil record. High-resolution data from 3.46-Ga Apex chert microbiota help us to test rigorous criteria for studying the early fossil record. Preservational windows in the 1.88-Ga Gunflint chert allow us to posit novel cellular forms, and emphasize the critical role played by the fossil record in understanding early biodiversity. Micromapping of 3.43-Ga Strelley Pool sandstone reveals microfossils preserved between sand grains from the earliest known shoreline, reminding us that many kinds of ancient habitat have yet to be explored in this way.
Convergence, divergence, and parallelism in marine biodiversity trends: Integrating present-day and fossil data
Authors: Huang Shan , Roy Kaustuv , Valentine James W. , Jablonski David 
Published: April 2015

SignificanceThe fossil record can reveal the complex history behind present-day diversity patterns. For marine bivalves, similarities and differences in species diversity within lineages among regions are better explained by past extinction, origination, and immigration than by contrasts in today’s climates alone. A signature of more severe extinction in the western Atlantic relative to the western Pacific coast is still evident in the tropics, but not in the temperate zone, where more prolific diversification and/or immigration has allowed the western Atlantic to match or surpass eastern Pacific diversities for many lineages. Species persistence in the temperate zone is associated with broad geographic range prior to an extinction pulse ∼2−3 My ago, underscoring the importance of history for understanding modern biodiversity patterns.
Predicting traffic volumes and estimating the effects of shocks in massive transportation systems
Authors: Silva Ricardo , Kang Soong Moon , Airoldi Edoardo M. 
Published: April 2015

SignificanceWe propose a new approach to analyzing massive transportation systems that leverages traffic information about individual travelers. The goals of the analysis are to quantify the effects of shocks in the system, such as line and station closures, and to predict traffic volumes. We conduct an in-depth statistical analysis of the Transport for London railway traffic system. The proposed methodology is unique in the way that past disruptions are used to predict unseen scenarios, by relying on simple physical assumptions of passenger flow and a system-wide model for origin–destination movement. The method is scalable, more accurate than blackbox approaches, and generalizable to other complex transportation systems. It therefore offers important insights to inform policies on urban transportation.
Heterogeneity of long-history migration explains cultural differences in reports of emotional expressivity and the functions of smiles
Authors: Rychlowska Magdalena , Miyamoto Yuri , Matsumoto David , Hess Ursula , Gilboa-Schechtman Eva , Kamble Shanmukh , Muluk Hamdi , Masuda Takahiko , Niedenthal Paula Marie 
Published: April 2015

Significance
In an age of globalization, emotional understanding is the central problem of human interaction. Here, we show that historical heterogeneity, or the extent to which a country’s present-day population descends from numerous (vs. few) source countries, predicts cultural variation in norms for emotional expressivity. Reanalysis of cultural display rules from 32 countries reveals that historical heterogeneity is associated with norms favoring greater emotional expressivity. In addition, the results of a study of nine countries show that the belief that smiles signal social bonding motives vs. the negotiation of status in a social hierarchy is predicted by historical heterogeneity as well.
Phytoplankton adapt to changing ocean environments
Authors: Irwin Andrew J. , Finkel Zoe V. , Müller-Karger Frank E. , Troccoli Ghinaglia Luis 
Published: April 2015

Significance
Most ecosystem models used to predict changes in community composition with climate change assume species’ responses to environmental conditions are genetically fixed on the century scale, but this hypothesis has not been tested. Using an oceanographic time series with directional environmental changes, we show here that many phytoplankton species are able to track, on average, modest changes in temperature and irradiance, but not decreases in limiting nutrient concentrations, on decadal timescales. This result suggests that models that use genetically fixed traits may not provide reasonable projections for changes in biological communities in response to climate change over decadal to longer timescales.
Amplified Arctic warming by phytoplankton under greenhouse warming
Authors: Park Jong-Yeon , Kug Jong-Seong , Bader Jürgen , Rolph Rebecca , Kwon Minho 
Published: April 2015

Significance
One of the important impacts of marine phytoplankton on climate systems is the geophysical feedback by which chlorophyll and the related pigments in phytoplankton absorb solar radiation and then change sea surface temperature. Yet such biogeophysical impact is still not considered in many climate projections by state-of-the-art climate models, nor is its impact on the future climate quantified. This study shows that, by conducting global warming simulations with and without an active marine ecosystem model, the biogeophysical effect of future phytoplankton changes amplifies Arctic warming by 20%. Given the close linkage between the Arctic and global climate, the biologically enhanced Arctic warming can significantly modify future estimates of global climate change, and therefore it needs to be considered as a possible future scenario.
Odorant receptors regulate the final glomerular coalescence of olfactory sensory neuron axons
Authors: Rodriguez-Gil Diego J. , Bartel Dianna L. , Jaspers Austin W. , Mobley Arie S. , Imamura Fumiaki , Greer Charles A. 
Published: April 2015

Significance
The constant generation of olfactory sensory neurons throughout life makes the system appealing for studies of the mechanisms of axon extension and connectivity. Understanding the mechanisms leading to the genesis of these new neurons is fundamental for the development of therapeutic treatments. We provide here, to our knowledge, the first detailed analysis of the sequential steps leading toward fully differentiated sensory neurons. We show that odorant receptors are not involved in the initial steps of differentiation, but only later in the final process of maturation. Moreover, the proteins that we studied here also have been implicated in normal and pathophysiological events ranging from kidney function to cancer development, making our data valuable across different disciplines.
Drought, agricultural adaptation, and sociopolitical collapse in the Maya Lowlands
Authors: Douglas Peter M. J. , Pagani Mark , Canuto Marcello A. , Brenner Mark , Hodell David A. , Eglinton Timothy I. , Curtis Jason H. 
Published: April 2015

Significance
The Terminal Classic decline of the Maya civilization represents a key example of ancient societal collapse that may have been caused by climate change, but there are inconsistencies between paleoclimate and archaeological evidence regarding the spatial distribution of droughts and sociopolitical disintegration. We conducted a new analysis of regional drought intensity that shows drought was most severe in the region with the strongest societal collapse. We also found that an earlier drought interval coincided with agricultural intensification, suggesting that the ancient Maya adapted to previous episodes of climate drying, but could not cope with the more extreme droughts of the Terminal Classic.
Tryptophan-to-heme electron transfer in ferrous myoglobins
Authors: Monni Roberto , Al Haddad André , van Mourik Frank , Auböck Gerald , Chergui Majed 
Published: April 2015

SignificanceWe demonstrate the occurrence of tryptophan (Trp) to heme electron transfer (ET) in ferrous myoglobins by ultrafast UV spectroscopy. The ET gives rise to the theoretically predicted, low-valence Fe(II)(porph●−) anion radical, which we observe for the first time to our knowledge under physiological conditions. These results highlight the generality of Trp–porphyrin electron transfer events in heme proteins and question the systematic use of Trp fluorescence in FRET studies of protein dynamics.
Endosymbiosis undone by stepwise elimination of the plastid in a parasitic dinoflagellate
Authors: Gornik Sebastian G. , Febrimarsa  , Cassin Andrew M. , MacRae James I. , Ramaprasad Abhinay , Rchiad Zineb , McConville Malcolm J. , Bacic Antony , McFadden Geoffrey I. , Pain Arnab , Waller Ross F. 
Published: April 2015

Significance
Endosymbiotic organelles are a defining feature of eukaryotes—the last common ancestor and all extant eukaryotes possess at least a mitochondrial derivative. Although mitochondria and plastids are identified with aerobic ATP synthesis and photosynthesis, respectively, their retention by their host cells requires the merging and integration of many, often redundant, metabolic pathways. As a result, complex metabolic interdependencies arise between these formerly independent cells. Complete loss of endosymbiotic organelles, even where aerobic respiration or photosynthesis is lost, is exceedingly difficult, as demonstrated by persistence of organelles throughout secondary anaerobes and parasites. Here, we identify a rare but clear case of plastid loss in a parasitic alga and detail the metabolic disentanglement that was required to achieve this exceptional evolutionary event.
Accessory NUMM (NDUFS6) subunit harbors a Zn-binding site and is essential for biogenesis of mitochondrial complex I
Authors: Kmita Katarzyna , Wirth Christophe , Warnau Judith , Guerrero-Castillo Sergio , Hunte Carola , Hummer Gerhard , Kaila Ville R. I. , Zwicker Klaus , Brandt Ulrich , Zickermann Volker 
Published: April 2015

Significance
Respiratory complex I is the largest membrane protein complex in mitochondria and has a central function in energy metabolism. Numerous human diseases are linked with complex I dysfunction or assembly defects. The concerted assembly of more than 40 subunits and the insertion of cofactors is aided by specific chaperones. In addition to eight FeS clusters, complex I comprises a Zn-binding site of unknown function. Combining X-ray structural analysis of complex I crystals with quantum chemical modeling and proteomic and spectroscopic analysis of a purified assembly intermediate, we show that accessory subunit NUMM (human ortholog NDUFS6) binds Zn at the interface of two functional modules of the enzyme complex and is required for a specific step of complex I biogenesis.
Comparative analyses of animal-tracking data reveal ecological significance of endothermy in fishes
Authors: Watanabe Yuuki Y. , Goldman Kenneth J. , Caselle Jennifer E. , Chapman Demian D. , Papastamatiou Yannis P. 
Published: April 2015

Significance
Most fishes are cold-blooded, but tunas and some sharks (e.g., white sharks) maintain their exercising muscles warmer than ambient waters. This ability is a remarkable example of convergent evolution because bony and cartilaginous fishes diverged as long as 450 million years ago. What are the ecological benefits driving the evolution of warm muscles in fishes? Despite extensive discussion, no previous studies have tested a simple possibility that fishes with warm muscles may swim faster in nature. We demonstrate that fishes with warm muscles swim faster and perform larger-scale annual migrations than similar-sized cold-blooded fishes. Our results suggest that warm muscles enhance power output and, thus, cruising speeds, which may enable longer-distance migrations and potentially greater access to seasonally available resources.
Organometallic rotaxane dendrimers with fourth-generation mechanically interlocked branches
Authors: Wang Wei , Chen Li-Jun , Wang Xu-Qing , Sun Bin , Li Xiaopeng , Zhang Yanyan , Shi Jiameng , Yu Yihua , Zhang Li , Liu Minghua , Yang Hai-Bo 
Published: April 2015

Significance
In this study, the preparation of organometallic rotaxane dendrimers with a well-defined topological structure and enhanced rigidity was developed. Starting from a simple rotaxane building block, high-generation rotaxane branched dendrimers were synthesized and characterized. The fourth-generation structure described is among the highest-generation organometallic rotaxane dendrimers reported to date. The introduction of pillar[5]arene rotaxane units activates dynamic features in the dendrimer and enhances the rigidity of each branch of the supermolecules. This research offers a facile approach to the construction of high-generation rotaxane branched dendrimer, which not only enriches the library of rotaxne dendrimer but also provides the further insight into their applications as supramolecular dynamic materials.
Kibble–Zurek mechanism in colloidal monolayers
Authors: Deutschländer Sven , Dillmann Patrick , Maret Georg , Keim Peter 
Published: April 2015

Significance
Spontaneous symmetry breaking describes a variety of transformations from high- to low-temperature phases and applies to cosmological concepts as well as atomic systems. T. W. B. Kibble suggested defect structures (domain walls, strings, and monopoles) to appear during the expansion and cooling of the early universe. The lack of such defects within the visible horizon of the universe mainly motivated inflationary Big Bang theories. W. H. Zurek pointed out that the same principles are relevant within the laboratory when a system obeying a second-order phase transition is cooled at finite rates into the low symmetry phase. Using a colloidal system, we visualize the Kibble–Zurek mechanism on single particle level and clarify its nature in the background of an established microscopic melting formalism.
Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus
Authors: Ebert Gregor , Preston Simon , Allison Cody , Cooney James , Toe Jesse G. , Stutz Michael D. , Ojaimi Samar , Scott Hamish W. , Baschuk Nikola , Nachbur Ueli , Torresi Joseph , Chin Ruth , Colledge Danielle , Li Xin , Warner Nadia , Revill Peter , Bowden Scott , Silke John , Begley C. Glenn , Pellegrini Marc 
Published: April 2015

SignificanceHepatitis B virus (HBV) causes substantial morbidity and mortality. A large proportion of infected individuals controls infection but does not completely eradicate HBV DNA from the liver, and flares in hepatitis can be precipitated by immunosuppression. A proportion of individuals never controls infection, and these people are at substantial risk of developing liver failure and liver cancer. Current therapies are not effective at eliminating virus, and there is a major interest in developing functional cures for HBV infection. We identified host cell signaling molecules that can restrict the ability to eradicate infected cells. These molecules can be therapeutically targeted, and drugs that interfere with the function of these host cell proteins may be useful therapies to promote clearance of HBV infection.
Fabrication of alumina filled hybrid buckypaper composites and their enhancement of microwave absorbing performance
Authors: Miao Hsin-Yuan , Liu Jih-Hsin , Saravanan L 
Published: April 2015

Abstract
Alumina (Al2O3)-filled multiwalled carbon nanotube buckypapers (BPs) with different Al2O3 loadings (5–50 wt%) were successfully synthesised. Structural and morphological analysis performed with x-ray diffraction and field-emission scanning electron microscopy, respectively, confirmed the presence of stable α-phase Al2O3 particles in the Al2O3-BP composites. The formation of flexible Al2O3-BP hybrid nanocomposites (5–15 wt%) was attributed to the strong interfacial polarisation and high conductivity; compared with pure Al2O3 and BP. The nanocomposites with optimised alumina loadings demonstrated enhanced microwave absorption (>90%) and a broader absorption bandwidth in the investigated high-frequency region.
A deep, unusual over-contact binary system with high rate of mass transfer: LP Ursa Major
Authors: Liao Wen-Ping , Qian Sheng-Bang , Zhao Er-Gang , Li Lin-Jia 
Published: April 2015

Abstract
We observed the well-known unusual deep over-contact binary in 2012 and 2013. A new set of light curves and eight new observed times of light minima were derived. A total of 130 available CCD times of light minima were analyzed. The highest rate of long-term period increase in W UMa stars (+10.21 s century−1) was confirmed. The rapid period increase implies that the primary is accreting mass from the secondary at a high rate of $\skew4\dot{M} = 5.3 \times 10^{-6}\,M_{\odot }\:$yr−1. The asymmetric light curves (i.e., the O'Connell effect) were analyzed with the Wilson–Devinney Code. It was found that the spotted photometric solution with the third light is the best one for fitting the light curves. The main photometric results confirmed that LP UMa is an unusual W UMa system with a high mass ratio (q = 0.823 ± 0.003), deep-contact configuration (f = 66.6% ± 3.1%), and a temperature difference of Δ T = 700 K. The period increase in LP UMa may be a part of a long-period cyclic change because of the large third light contributions to the total system (61.52% in V, 61.39% in R, and 61.36% in I). All of these quite different properties make LP UMa a very interesting system to study. The possible evolutionary stage is also discussed.
Modelling nanoflares in active regions and implications for coronal heating mechanisms
Authors: Cargill P. J. , Warren H. P. , Bradshaw S. J. 
Published: April 2015

Recent observations from the Hinode and Solar Dynamics Observatory spacecraft have provided major advances in understanding the heating of solar active regions (ARs). For ARs comprising many magnetic strands or sub-loops heated by small, impulsive events (nanoflares), it is suggested that (i) the time between individual nanoflares in a magnetic strand is 500–2000 s, (ii) a weak ‘hot’ component (more than 10
6.6
K) is present, and (iii) nanoflare energies may be as low as a few 10
23
ergs. These imply small heating events in a stressed coronal magnetic field, where the time between individual nanoflares on a strand is of order the cooling time. Modelling suggests that the observed properties are incompatible with nanoflare models that require long energy build-up (over 10 s of thousands of seconds) and with steady heating.
On building social capital for Islamic finance
Authors: Ng Adam , Ibrahim Mansor , Mirakhor Abbas 
Published: April 2015

Purpose– The purpose of this paper is to set forth seven broad recommendations and 15 specific initiatives within a four-dimensional framework for the development of social capital in Islamic finance, particularly the stock market, given its role as the first best means of risk sharing.Design/methodology/approach– The four-dimensional framework comprises dimensions of principle and value, trust-reinforcing regulation, investment opportunity and infrastructure, as well as reputational intermediaries.Findings– A web of multi-pronged initiatives that are mutually reinforcing is proposed considering the multifaceted dimensions of social capital and the various possible transmission channels by which social capital can influence the financial system.Practical implications– While empirical studies have demonstrated the importance of trust and ethics in financial development, the pressing issue remains how social capital, including trust and ethics, can be developed to achieve a trustworthy, ethical and efficient financial system. This paper attempts to address this concern.Originality/value– This paper provides a framework for building social capital in Islamic finance.