bluuebunny/crossref_metadata_2025_split huggingface dataset:
Calcium-induced conformational changes of the regulatory domain of human mitochondrial aspartate/glutamate carriers
Authors: Thangaratnarajah Chancievan , Ruprecht Jonathan J. , Kunji Edmund R. S. 
Published: November 2014

AbstractThe transport activity of human mitochondrial aspartate/glutamate carriers is central to the malate–aspartate shuttle, urea cycle, gluconeogenesis and myelin synthesis. They have a unique three-domain structure, comprising a calcium-regulated N-terminal domain with eight EF-hands, a mitochondrial carrier domain, and a C-terminal domain. Here we present the calcium-bound and calcium-free structures of the N- and C-terminal domains, elucidating the mechanism of calcium regulation. Unexpectedly, EF-hands 4–8 are involved in dimerization of the carrier and form a static unit, whereas EF-hands 1–3 form a calcium-responsive mobile unit. On calcium binding, an amphipathic helix of the C-terminal domain binds to the N-terminal domain, opening a vestibule. In the absence of calcium, the mobile unit closes the vestibule. Opening and closing of the vestibule might regulate access of substrates to the carrier domain, which is involved in their transport. These structures provide a framework for understanding cases of the mitochondrial disease citrin deficiency.
Microhomology-mediated end-joining-dependent integration of donor DNA in cells and animals using TALENs and CRISPR/Cas9
Authors: Nakade Shota , Tsubota Takuya , Sakane Yuto , Kume Satoshi , Sakamoto Naoaki , Obara Masanobu , Daimon Takaaki , Sezutsu Hideki , Yamamoto Takashi , Sakuma Tetsushi , Suzuki Ken-ichi T. 
Published: November 2014

AbstractGenome engineering using programmable nucleases enables homologous recombination (HR)-mediated gene knock-in. However, the labour used to construct targeting vectors containing homology arms and difficulties in inducing HR in some cell type and organisms represent technical hurdles for the application of HR-mediated knock-in technology. Here, we introduce an alternative strategy for gene knock-in using transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) mediated by microhomology-mediated end-joining, termed the PITCh (Precise Integration into Target Chromosome) system. TALEN-mediated PITCh, termed TAL-PITCh, enables efficient integration of exogenous donor DNA in human cells and animals, including silkworms and frogs. We further demonstrate that CRISPR/Cas9-mediated PITCh, termed CRIS-PITCh, can be applied in human cells without carrying the plasmid backbone sequence. Thus, our PITCh-ing strategies will be useful for a variety of applications, not only in cultured cells, but also in various organisms, including invertebrates and vertebrates.
Cell death induced by ozone and various non-thermal plasmas: therapeutic perspectives and limitations
Authors: Lunov Oleg , Zablotskii Vitalii , Churpita Olexander , Chánová Eliška , Syková Eva , Dejneka Alexandr , Kubinová Šárka 
Published: November 2014

AbstractNon-thermal plasma has been recognized as a promising tool across a vast variety of biomedical applications, with the potential to create novel therapeutic methods. However, the understanding of the molecular mechanisms behind non-thermal plasma cellular effects remains a significant challenge. In this study, we show how two types of different non-thermal plasmas induce cell death in mammalian cell cultures via the formation of multiple intracellular reactive oxygen/nitrogen species. Our results showed a discrepancy in the superoxide accumulation and lysosomal activity in response to air and helium plasma, suggesting that triggered signalling cascades might be grossly different between different plasmas. In addition, the effects of ozone, a considerable component of non-thermal plasma, have been simultaneously evaluated and have revealed much faster and higher cytotoxic effects. Our findings offer novel insight into plasma-induced cellular responses and provide a basis for better controlled biomedical applications.
VEGF-B selectively regenerates injured peripheral neurons and restores sensory and trophic functions
Authors: Guaiquil Victor H. , Pan Zan , Karagianni Natalia , Fukuoka Shima , Alegre Gemstonn , Rosenblatt Mark I. 
Published: November 2014

Significance
Peripheral nerve injury is a major neurological disorder that can cause multiple motor and sensory disturbances. In this study we found that VEGF-B can be used as a previously unidentified therapeutic for treating peripheral nerve injury. We demonstrated that VEGF-B stimulated nerve regeneration and enhanced the recovery of both tissue sensation and the ability of nerves to enhance healing of innervated tissue. The physiologic relevance of VEGF-B is demonstrated by our findings showing that mice lacking VEGF-B have impaired nerve regeneration and that nerve injury resulted in increased endogenous expression of VEGF-B. We discover that VEGF-B induces strong elongation and branching of neurons and requires specific transmembrane receptors as well as activation of a complex intracellular signaling.
Ethnic diversity deflates price bubbles
Authors: Levine Sheen S. , Apfelbaum Evan P. , Bernard Mark , Bartelt Valerie L. , Zajac Edward J. , Stark David 
Published: November 2014

SignificanceMarkets are central to modern society, so their failures can have devastating effects. Here, we examine a prominent failure: price bubbles. We propose that bubbles are affected by ethnic homogeneity in the market and can be thwarted by diversity. Using experimental markets in Southeast Asia and North America, we find a marked difference: Market prices fit true values 58% better in diverse markets. In homogenous markets, overpricing is higher and traders’ errors are more correlated than in diverse markets. The findings suggest that price bubbles arise not only from individual errors or financial conditions, but also from the social context of decision making. Informing public discussion, our findings suggest that diversity facilitates friction that enhances deliberation and upends conformity.
Rapid climate change did not cause population collapse at the end of the European Bronze Age
Authors: Armit Ian , Swindles Graeme T. , Becker Katharina , Plunkett Gill , Blaauw Maarten 
Published: November 2014

Significance
The impact of rapid climate change on humans is of contemporary global interest. Present-day debates are necessarily informed by paleoclimate studies in which climate is often assumed, without sufficient critical attention, to be the primary driver of societal change. Using new methods to analyze paleoclimatic and archeological datasets, we overturn the deterministic idea that population collapse at the end of the northwestern European Bronze Age was caused by rapid climate change. Our work demonstrates the necessity of high-precision chronologies in evaluating human responses to rapid climate change. It will be significant for geoscientists, climate change scientists, and archeologists.
Harm to others outweighs harm to self in moral decision making
Authors: Crockett Molly J. , Kurth-Nelson Zeb , Siegel Jenifer Z. , Dayan Peter , Dolan Raymond J. 
Published: November 2014

Significance
Concern for the welfare of others is a key component of moral decision making and is disturbed in antisocial and criminal behavior. However, little is known about how people evaluate the costs of others’ suffering. Past studies have examined people’s judgments in hypothetical scenarios, but there is evidence that hypothetical judgments cannot accurately predict actual behavior. Here we addressed this issue by measuring how much money people will sacrifice to reduce the number of painful electric shocks delivered to either themselves or an anonymous stranger. Surprisingly, most people sacrifice more money to reduce a stranger’s pain than their own pain. This finding may help us better understand how people resolve moral dilemmas that commonly arise in medical, legal, and political decision making.
Transition from geostrophic turbulence to inertia–gravity waves in the atmospheric energy spectrum
Authors: Callies Jörn , Ferrari Raffaele , Bühler Oliver 
Published: November 2014

Significance
High- and low-pressure systems, commonly referred to as synoptic systems, are the most energetic fluctuations of wind and temperature in the midlatitude troposphere. Synoptic systems are a few thousand kilometers in scale and are governed by a balance between the pressure gradient force and the Coriolis force. Observations collected near the tropopause by commercial aircraft indicate a change in dynamics at horizontal scales smaller than about 500 km. Smaller-scale fluctuations are shown to be dominated by inertia–gravity waves, waves that propagate on vertical density gradients but are influenced by Earth’s rotation.
Relating influenza virus membrane fusion kinetics to stoichiometry of neutralizing antibodies at the single-particle level
Authors: Otterstrom Jason J. , Brandenburg Boerries , Koldijk Martin H. , Juraszek Jarek , Tang Chan , Mashaghi Samaneh , Kwaks Ted , Goudsmit Jaap , Vogels Ronald , Friesen Robert H. E. , van Oijen Antoine M. 
Published: November 2014

Significance
We determine the number of broadly neutralizing antibodies required to inhibit influenza virus membrane fusion by simultaneously observing individual viral particles undergoing fusion and counting the number of antibodies bound to them. The viral membrane fusion process is mediated by fusion proteins whose activity is blocked through the binding of these antibodies to evolutionarily conserved epitopes. Surprisingly, the number of antibodies required for inhibition is markedly lower than the number of fusion proteins present, indicating virus neutralization does not require saturation of epitope occupancy. Overall, our results support a model of membrane fusion requiring several fusion proteins working together in a coordinated, stochastic fashion, and the inhibition of this process through disruption of fusion protein coordination.
Noise decomposition of intracellular biochemical signaling networks using nonequivalent reporters
Authors: Rhee Alex , Cheong Raymond , Levchenko Andre 
Published: November 2014

Significance
In response to a uniform stimulus, biochemical networks display a high degree of variability when assayed across many individual cells. However, due to their complexity, the relative contributions of different pathways to the overall network variability are hard to evaluate and control. Here we introduce a technique allowing for “noise mapping” to be performed within such networks. By experimentally assaying three distinct tumor necrosis factor (TNF) activated transcription factors within a mathematical framework, we show how noise is distributed in the TNF-induced network, in the presence or absence of feedback. This framework is readily scalable to allow the noise decomposition of larger and more complex signaling networks, permitting further investigations into the dependence of biological noise on signaling system architecture.
Impact of circadian misalignment on energy metabolism during simulated nightshift work
Authors: McHill Andrew W. , Melanson Edward L. , Higgins Janine , Connick Elizabeth , Moehlman Thomas M. , Stothard Ellen R. , Wright Kenneth P. 
Published: November 2014

SignificanceDemands of modern society force many work operations into the night, when the intrinsic circadian timing system promotes sleep. Overnight shiftwork is associated with increased risk for adverse metabolic health and sleep disruption. Uncovering potential physiological mechanisms that contribute to metabolic dysregulation when work and eating occur at inappropriate circadian times is vital to the development of effective treatment strategies. In this study, healthy volunteers underwent a commonly used simulated shiftwork protocol to quantify changes in metabolic, sleep, and circadian physiology when working and eating during the night as compared with a traditional day work schedule. We demonstrate that nightshift work reduces total daily energy expenditure, representing a contributing mechanism for unwanted weight gain and obesity.
Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion
Authors: Schwartz Christian , Turqueti-Neves Adriana , Hartmann Susanne , Yu Philipp , Nimmerjahn Falk , Voehringer David 
Published: November 2014

Significance
Gastrointestinal worms (helminths) infect more than 2 billion people, and vaccines are not yet available. Helminths elicit a type 2 immune response characterized by high serum IgE levels and increased numbers of IL-4– or IL-13–secreting effector cells including Th2 cells, eosinophils, basophils, and type 2 innate lymphoid cells. We determined the mechanism by which basophils contribute to protection against secondary infections with gastrointestinal helminths. Here we demonstrate that basophils are recruited into the small intestine of infected mice and orchestrate the local type 2 immune response in this tissue. Basophil-mediated protection required the presence of IgE and the expression of activating Fc receptors and IL-4/IL-13 in basophils. These findings could help the development of new vaccination strategies against helminths.
Structures of protective antibodies reveal sites of vulnerability on Ebola virus
Authors: Murin Charles D. , Fusco Marnie L. , Bornholdt Zachary A. , Qiu Xiangguo , Olinger Gene G. , Zeitlin Larry , Kobinger Gary P. , Ward Andrew B. , Saphire Erica Ollmann 
Published: November 2014

Significance
Ebola virus causes lethal hemorrhagic fever, and the current 2014 outbreak in western Africa is the largest on record to date. No vaccines or therapeutics are yet approved for human use. Therapeutic antibody cocktails, however, have shown efficacy against otherwise lethal Ebola virus infection and show significant promise for eventual human use. Here we provide structures of every mAb in the ZMapp cocktail, as well as additional antibodies from the MB-003 and ZMAb cocktails from which ZMapp was derived, each in complex with the Ebola glycoprotein. The set of structures illustrates sites of vulnerability of Ebola virus, and importantly, provides a roadmap to determine their mechanism of protection and for ongoing selection and improvement of immunotherapeutic cocktails against the filoviruses.
Charging-free electrochemical system for harvesting low-grade thermal energy
Authors: Yang Yuan , Lee Seok Woo , Ghasemi Hadi , Loomis James , Li Xiaobo , Kraemer Daniel , Zheng Guangyuan , Cui Yi , Chen Gang 
Published: November 2014

Significance
Tremendous low-grade heat is stored in industrial processes and the environment. Efficient and low-cost utilization of the low-grade heat is critical to imminent energy and environmental challenges. Here, a rechargeable electrochemical cell (battery) is used to harvest such thermal energy because its voltage changes significantly with temperature. Moreover, by carefully tuning the composition of electrodes, the charging process is purely powered by thermal energy and no electricity is required to charge it. A high heat-to-electricity conversion efficiency of 2.0% can be reached when it is operated between 20 and 60 °C. Such charging-free characteristic may have potential application for harvesting low-grade heat from the environment, especially in remote areas.
Orientation of aromatic residues in amyloid cores: Structural insights into prion fiber diversity
Authors: Reymer Anna , Frederick Kendra K. , Rocha Sandra , Beke-Somfai Tamás , Kitts Catherine C. , Lindquist Susan , Nordén Bengt 
Published: November 2014

Significance
Amyloids, which are protein fiber aggregates, are often associated with neurodegenerative diseases such as Alzheimer’s, but they can also be beneficial, as in yeasts, where they help cells adapt to environmental changes. Intriguingly, the same protein has the ability to aggregate into different fiber forms, known as strains, that generate distinct biological phenotypes. Structurally, little is known about strains. Using polarized light spectroscopy, we provide structural information on two distinct phenotypic strains of the yeast translation termination factor, Sup35. Remarkably, they show similar orientation of aromatic residues in the fiber core relative to the fiber direction, suggesting similar structures. Small variations are observed, indicating different local environments for aromatic residues outside the core, reflecting differences in fiber packing.
The vertical occipital fasciculus: A century of controversy resolved by in vivo measurements
Authors: Yeatman Jason D. , Weiner Kevin S. , Pestilli Franco , Rokem Ariel , Mezer Aviv , Wandell Brian A. 
Published: November 2014

Significance
The vertical occipital fasciculus (VOF) is a major white-matter fascicle connecting dorsal and ventral visual cortex. Few vision scientists or cognitive neuroscientists are aware of the VOF's existence. The scarcity of papers on this important pathway stems from the contentious history surrounding its discovery by Wernicke in 1881. We review the conflict surrounding the classic, postmortem, VOF measurements, and we introduce modern, in vivo methods to precisely characterize the VOF's cortical terminations and unique tissue properties. The new VOF measurements provide insight into the communication between ventral stream regions involved in form perception and dorsal stream regions involved in eye movements and attention.
The commonly used antimicrobial additive triclosan is a liver tumor promoter
Authors: Yueh Mei-Fei , Taniguchi Koji , Chen Shujuan , Evans Ronald M. , Hammock Bruce D. , Karin Michael , Tukey Robert H. 
Published: November 2014

Significance
Triclosan [5-chloro-2-(2,4-dichlorophenoxy)phenol; TCS] is a broad-spectrum antimicrobial agent that has become one of the most common additives used in consumer products. As a result, TCS has significantly affected the environment and has been frequently detected in human body fluids. Through a long-term feeding study, we found that TCS enhances hepatocyte proliferation, fibrogenesis, and oxidative stress, which, we believe, can be the driving force for developing advanced liver disease in mice. Indeed, TCS strongly enhances hepatocarcinogenesis after diethylnitrosamine initiation, accelerating hepatocellular carcinoma (HCC) development. Although animal studies require higher chemical concentrations than predicted for human exposure, this study demonstrates that TCS acts as a HCC tumor promoter and that the mechanism of TCS-induced mouse liver pathology may be relevant to humans.
Inhibition of tumor cell proliferation and motility by fibroblasts is both contact and soluble factor dependent
Authors: Alkasalias Twana , Flaberg Emilie , Kashuba Vladimir , Alexeyenko Andrey , Pavlova Tatiana , Savchenko Andrii , Szekely Laszlo , Klein George , Guven Hayrettin 
Published: November 2014

Significance
Normal microenvironments can restrict cancer development and progression. Inhibition of tumor cell growth and motility by normal fibroblasts is one measurable manifestation of this multicomponential control. Here we show that inhibition withstands formalin fixation and can be augmented by the addition of conditioned medium derived from live cultures of tumor cells confronting the stromal fibroblasts. We describe a number of molecules involved in this process. This study lays the foundation for further mechanistic studies of this important phenomenon and its contribution to possible dormancy and the tumor’s resistance to therapy.
RecQ helicase and RecJ nuclease provide complementary functions to resect DNA for homologous recombination
Authors: Morimatsu Katsumi , Kowalczykowski Stephen C. 
Published: November 2014

Significance
Breaks in DNA are repaired by homologous recombination. Because the structure of DNA ends at a break site can be variable, the repair machinery must be designed to act on a variety of heterogeneous DNA break sites. Bacterial RecQ helicase and RecJ nuclease initiate the repair of double-stranded DNA breaks; however, neither protein alone can deal with the broad range of physiological ends. Human Bloom syndrome helicase (BLM) is the homolog of RecQ, and it functions in DNA resection, contributing to genomic stability in humans. We establish that RecQ and RecJ complement one another by acting on DNA ends and intermediates that the other cannot. Thus, by leveraging complementary substrate preferences, recombination initiation from all types of DNA ends, in many organisms, is ensured.
Agonists of growth hormone-releasing hormone stimulate self-renewal of cardiac stem cells and promote their survival
Authors: Florea Victoria , Majid Sonia S. , Kanashiro-Takeuchi Rosemeire M. , Cai Ren-Zhi , Block Norman L. , Schally Andrew V. , Hare Joshua M. , Rodrigues Claudia O. 
Published: November 2014

Significance
Stem cell therapy is an emerging approach to the treatment of heart failure. Endogenous or transplanted stem cells have limited repair capacity due to damage by exposure to stress. Agonists of growth hormone-releasing hormone receptor (GHRH-R) have been previously shown to increase the number of endogenous cardiac stem cells (CSCs) after myocardial infarction; enhance vasculogenesis of mesenchymal stem cells; and improve growth, engraftment, and survival of transplanted pancreatic islets in experimental models. This study shows that CSCs isolated from different species express GHRH-R and agonists of GHRH-R stimulate their proliferation and survival. Our findings support the potential use of GHRH agonists for endogenous stem cell stimulation and preconditioning prior to transplantation to improve CSC mobilization, survival, and probably enhancement of their angiomyogenic potential in the infarcted myocardium.
Combinatorial regulation of a signal-dependent activator by phosphorylation and acetylation
Authors: Paz Jose C. , Park Sangho , Phillips Naomi , Matsumura Shigenobu , Tsai Wen-Wei , Kasper Lawryn , Brindle Paul K. , Zhang Guangtao , Zhou Ming-Ming , Wright Peter E. , Montminy Marc 
Published: November 2014

Significance
Catecholamines regulate adipocyte function in part by CREB activation. Obesity displays enhanced cyclic AMP response element binding protein (CREB) activity despite reduced catecholamine signals. We report that obesity promotes CREB binding protein (CBP)-mediated CREB acetylation at Lys136 in the adipose tissue by means of reduced SirT1 levels. CREB Lys136 acetylation promotes binding with the bromodomain (BRD) of CBP, which can also bind phosphorylated Ser133, through its KIX domain, upon hormonal signals. This double recognition is reflected in potentiated CBP recruitment at promoters when CREB is doubly modified. Structural data show the formation of a ternary complex between CBP BRD and KIX domains when bound to phospho-Ser133 and acetylated-Lys136 CREB. Disruption of the BRD:CREB interaction with a small molecule reduced the enhanced CREB activity associated with acetylation.