bluuebunny/crossref_metadata_2025_split huggingface dataset:
Detection of single ion channel activity with carbon nanotubes
Authors: Zhou Weiwei , Wang Yung Yu , Lim Tae-Sun , Pham Ted , Jain Dheeraj , Burke Peter J. 
Published: March 2015

AbstractMany processes in life are based on ion currents and membrane voltages controlled by a sophisticated and diverse family of membrane proteins (ion channels), which are comparable in size to the most advanced nanoelectronic components currently under development. Here we demonstrate an electrical assay of individual ion channel activity by measuring the dynamic opening and closing of the ion channel nanopores using single-walled carbon nanotubes (SWNTs). Two canonical dynamic ion channels (gramicidin A (gA) and alamethicin) and one static biological nanopore (α-hemolysin (α-HL)) were successfully incorporated into supported lipid bilayers (SLBs, an artificial cell membrane), which in turn were interfaced to the carbon nanotubes through a variety of polymer-cushion surface functionalization schemes. The ion channel current directly charges the quantum capacitance of a single nanotube in a network of purified semiconducting nanotubes. This work forms the foundation for a scalable, massively parallel architecture of 1d nanoelectronic devices interrogating electrophysiology at the single ion channel level.
Predicting long-term outcome of Internet-delivered cognitive behavior therapy for social anxiety disorder using fMRI and support vector machine learning
Authors: Månsson K N T , Frick A , Boraxbekk C-J , Marquand A F , Williams S C R , Carlbring P , Andersson G , Furmark T 
Published: March 2015

AbstractCognitive behavior therapy (CBT) is an effective treatment for social anxiety disorder (SAD), but many patients do not respond sufficiently and a substantial proportion relapse after treatment has ended. Predicting an individual’s long-term clinical response therefore remains an important challenge. This study aimed at assessing neural predictors of long-term treatment outcome in participants with SAD 1 year after completion of Internet-delivered CBT (iCBT). Twenty-six participants diagnosed with SAD underwent iCBT including attention bias modification for a total of 13 weeks. Support vector machines (SVMs), a supervised pattern recognition method allowing predictions at the individual level, were trained to separate long-term treatment responders from nonresponders based on blood oxygen level-dependent (BOLD) responses to self-referential criticism. The Clinical Global Impression-Improvement scale was the main instrument to determine treatment response at the 1-year follow-up. Results showed that the proportion of long-term responders was 52% (12/23). From multivariate BOLD responses in the dorsal anterior cingulate cortex (dACC) together with the amygdala, we were able to predict long-term response rate of iCBT with an accuracy of 92% (confidence interval 95% 73.2–97.6). This activation pattern was, however, not predictive of improvement in the continuous Liebowitz Social Anxiety Scale—Self-report version. Follow-up psychophysiological interaction analyses revealed that lower dACC–amygdala coupling was associated with better long-term treatment response. Thus, BOLD response patterns in the fear-expressing dACC–amygdala regions were highly predictive of long-term treatment outcome of iCBT, and the initial coupling between these regions differentiated long-term responders from nonresponders. The SVM-neuroimaging approach could be of particular clinical value as it allows for accurate prediction of treatment outcome at the level of the individual.
Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages
Authors: McClellan James Scott , Dove Christopher , Gentles Andrew J. , Ryan Christine E. , Majeti Ravindra 
Published: March 2015

Significance
Precursor B cell acute lymphoblastic leukemia (B-ALL) is an aggressive cancer of white blood cells with a poor prognosis. The cancerous cells in this disease are immature B cells, which are unable to fully differentiate into normal B cells. We show here that cancerous cells from B-ALL patients can be reprogrammed, causing them to change into cells that resemble normal macrophages and can perform macrophage-associated functions such as the consumption of bacteria. Importantly, unlike typical B-ALL cells, these reprogrammed cells are no longer able to cause disease in immunodeficient mice. Finally, we show that this reprogramming process may occur to some degree in patients with B-ALL. This indicates that reprogramming B-ALL cells into macrophages might represent a previously unidentified therapeutic strategy.
Biasing moral decisions by exploiting the dynamics of eye gaze
Authors: Pärnamets Philip , Johansson Petter , Hall Lars , Balkenius Christian , Spivey Michael J. , Richardson Daniel C. 
Published: March 2015

SignificanceWhere people look generally reflects and reveals their moment-by-moment thought processes. This study introduces an experimental method whereby participants’ eye gaze is monitored and information about their gaze is used to change the timing of their decisions. Answers to difficult moral questions such as “Is murder justifiable?” can be influenced toward random alternatives based on looking patterns alone. We do this without presenting different arguments or response frames, as in other techniques of persuasion. Thus, the process of arriving at a moral decision is not only reflected in a participant’s eye gaze but can also be determined by it.
Neuropeptide Y stimulates autophagy in hypothalamic neurons
Authors: Aveleira Célia A. , Botelho Mariana , Carmo-Silva Sara , Pascoal Jorge F. , Ferreira-Marques Marisa , Nóbrega Clévio , Cortes Luísa , Valero Jorge , Sousa-Ferreira Lígia , Álvaro Ana R. , Santana Magda , Kügler Sebastian , Pereira de Almeida Luís , Cavadas Cláudia 
Published: March 2015

Significance
Autophagy impairment is a major hallmark of aging, and any intervention that enhances autophagy is of potential interest to delay aging. However, it was described that the hypothalamus is a brain area with a key role on whole-body aging. In the present study, we show that an endogenous molecule produced by the hypothalamus, the neuropeptide Y (NPY), stimulates autophagy in rodent hypothalamus. Because both hypothalamic autophagy and NPY levels decrease with age, a better understanding of hypothalamic neuronal autophagy regulation by NPY may provide new putative therapeutic strategies to ameliorate age-related deteriorations and delay aging.
Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function
Authors: Tripathi Abhishek , Vana P. Geoff , Chavan Tanmay S. , Brueggemann Lioubov I. , Byron Kenneth L. , Tarasova Nadya I. , Volkman Brian F. , Gaponenko Vadim , Majetschak Matthias 
Published: March 2015

Significanceα1-Adrenergic receptors are important for the regulation of vascular function and are targeted clinically for blood pressure control. Here, we provide evidence that α1A/B-adrenergic receptors (AR) form heteromeric complexes with chemokine (C-X-C motif) receptor 4 (CXCR4) on the cell surface of vascular smooth muscle cells. We show that disruption of α1A/B-AR:CXCR4 heteromeric complexes inhibits α1-AR–mediated functions in vascular smooth muscle cells and that treatment with CXCR4 agonists enhances the potency of the α1-AR agonist phenylephrine to increase blood pressure. These findings extend the current understanding of the molecular mechanisms regulating α1-AR and provide an example of G protein-coupled receptor heteromerization with important functional implications. Compounds targeting the α1A/B-AR:CXCR4 interaction could provide an alternative pharmacological approach to modulating blood pressure.
Prosurvival Bcl-2 family members reveal a distinct apoptotic identity between conventional and plasmacytoid dendritic cells
Authors: Carrington Emma M. , Zhang Jian-Guo , Sutherland Robyn M. , Vikstrom Ingela B. , Brady Jamie L. , Soo Priscilla , Vremec David , Allison Cody , Lee Erinna F. , Fairlie W. Douglas , Bouillet Philippe , Grabow Stephanie , Ottina Eleonora , Herold Marco J. , Pellegrini Marc , Huang David C. S. , Tarlinton David M. , Strasser Andreas , Lew Andrew M. , Zhan Yifan 
Published: March 2015

Significance
Dendritic cells (DCs) are pivotal for immune responses as they present antigens to T cells. Different DC subsets have different functions and are associated with different diseases. For example, plasmacytoid DCs (pDCs) produce type 1 interferons and are associated with the autoimmune disease, systemic lupus erythematosus. Understanding control of survival/apoptosis in different DC subsets may not only provide a molecular basis for their homeostasis but also guide therapeutic intervention of immunopathology. We revealed that two major DC subsets (pDCs and conventional DCs) express distinct BCL-2 family proteins at different levels and this correlated with their survival requirements. Accordingly, clinically applicable antagonist drugs killed the appropriate DC subsets, informing on the future use of these compounds for treating immune-mediated damage.
Double-stranded DNA translocase activity of transcription factor TFIIH and the mechanism of RNA polymerase II open complex formation
Authors: Fishburn James , Tomko Eric , Galburt Eric , Hahn Steven 
Published: March 2015

Significance
How ATP hydrolysis is coupled to promoter DNA unwinding and open complex formation at RNA polymerase II (Poll II) promoters is a longstanding question. Of the multisubunit RNA polymerases, only Pol II requires ATP for DNA unwinding. Here we show that the general transcription factor TFIIH subunit Ssl2 is a double-stranded DNA translocase. These and other data suggest that Ssl2 promotes DNA opening by tracking along the nontemplate promoter strand, rotating and inserting DNA into the Pol II active site cleft, leading to DNA unwinding. Our accompanying biochemical studies explain why the open complex is unstable and how TFIIH can promote Pol II escape from the promoter. Our findings also have important implications for the mechanism of TFIIH-mediated DNA repair.
Glucocorticoid-resistant Th17 cells are selectively attenuated by cyclosporine A
Authors: Schewitz-Bowers Lauren P. , Lait Philippa J. P. , Copland David A. , Chen Ping , Wu Wenting , Dhanda Ashwin D. , Vistica Barbara P. , Williams Emily L. , Liu Baoying , Jawad Shayma , Li Zhiyu , Tucker William , Hirani Sima , Wakabayashi Yoshiyuki , Zhu Jun , Sen Nida , Conway-Campbell Becky L. , Gery Igal , Dick Andrew D. , Wei Lai , Nussenblatt Robert B. , Lee Richard W. J. 
Published: March 2015

Significance
Cyclosporine A was one of the first drugs used in clinical practice to successfully rescue glucocorticoid-resistant inflammatory diseases. In this article we extend the characterization of glucocorticoid-resistant human Th17 cells, and demonstrate that this effector memory T-cell subset is reciprocally attenuated by cyclosporine A. This therapeutic paradigm was confirmed in a murine model of autoimmunity, refining our understanding of cyclosporine A’s effect on the adaptive immune response. These data support the rationale for Th17-targeting therapies in the treatment of glucocorticoid-resistant inflammation.
Altered cofactor regulation with disease-associated p97/VCP mutations
Authors: Zhang Xiaoyi , Gui Lin , Zhang Xiaoyan , Bulfer Stacie L. , Sanghez Valentina , Wong Daniel E. , Lee YouJin , Lehmann Lynn , Lee James Siho , Shih Pei-Yin , Lin Henry J. , Iacovino Michelina , Weihl Conrad C. , Arkin Michelle R. , Wang Yanzhuang , Chou Tsui-Fen 
Published: March 2015

SignificanceAge-associated degenerative diseases have similar pathogenic mechanisms related to defects in protein homeostasis. p97/VCP (valosin-containing protein) is essential for coordinating protein degradation and is mutated in a multisystem degenerative disease that affects the central nervous system, muscle, and bone. p97/VCP is an enzyme in the AAA ATPases (ATPases associated with diverse cellular activities) family, which takes apart ATP and uses this energy to perform pivotal functions. We found that p97/VCP cofactors control its enzymatic activity. p97/VCP disease mutants behave abnormally due to lack of appropriate control by these cofactors. Correcting the function of the disease-associated proteins may be a desirable approach to developing safe treatment for fatal degenerative diseases. The next steps are to screen and characterize large panels of compounds to identify potential drugs that may correct the malfunction.
Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3
Authors: Donovan Jesse , Whitney Gena , Rath Sneha , Korennykh Alexei 
Published: March 2015

Significance
Double-stranded RNA (dsRNA) is a pathogen-associated molecular pattern that triggers the type-I interferon (IFN) response in mammalian cells. The IFN response up-regulates several dsRNA sensors, including closely related oligoadenylate synthetases (OAS). The functional roles of different oligoadenylate synthetases in dsRNA surveillance are not understood. Here, we use X-ray crystallography and biochemistry to demonstrate that human OAS1 and OAS3 recognize dsRNA molecules of different length. We show that domain duplication accompanied by a loss of catalytic activity provides the mechanism for sensing long dsRNA by OAS3. Our studies thus reveal different functions of OAS1 and OAS3 in dsRNA surveillance, identify a key role of domain duplication in the OAS family, and advance the fundamental understanding of the human innate immune system.
Half-century evidence from western Canada shows forest dynamics are primarily driven by competition followed by climate
Authors: Zhang Jian , Huang Shongming , He Fangliang 
Published: March 2015

Significance
Forests worldwide have undergone rapid changes; however, understanding the causes of the changes has been a challenge. Climate on the regional scale has been overwhelmingly presumed to drive these changes, with little attention paid to the possible effects of competition. We compiled a long-term forest dataset from western Canada to study the relative importance of climate change and competition on tree growth, mortality, and recruitment. We showed that competition was the primary factor causing the long-term changes. Regional climate had a weaker yet significant effect on tree mortality, but no effect on tree growth and recruitment. This finding suggests that forest studies focused solely on the effects of climate may overlook the effect of other processes critical to forest dynamics.
Surface biosignatures of exo-Earths: Remote detection of extraterrestrial life
Authors: Hegde Siddharth , Paulino-Lima Ivan G. , Kent Ryan , Kaltenegger Lisa , Rothschild Lynn 
Published: March 2015

Significance
We develop the first catalogue, to our knowledge, of reflectance spectra for a diverse range of pigmented microorganisms, including ones that were isolated from Earth’s most extreme environments. This catalogue provides a broad scope of surface signatures for life on exoplanets, which could provide different conditions from those on Earth, allowing, for example, extremophiles on Earth to become the predominant life form. Much of the history of life on Earth has been dominated by microbial life, and it is likely that life on exoplanets evolves through single-celled stages prior to multicellular creatures. Here, we present the first database, to our knowledge, for such surface features in preparation for the next generation of space- and ground-based telescopes that will search for a wide variety of life on exoplanets.
A 17-My-old whale constrains onset of uplift and climate change in east Africa
Authors: Wichura Henry , Jacobs Louis L. , Lin Andrew , Polcyn Michael J. , Manthi Fredrick K. , Winkler Dale A. , Strecker Manfred R. , Clemens Matthew 
Published: March 2015

SignificanceAn enigmatic fossil representing the deep-diving, open-ocean whale family Ziphiidae found 740 km inland and at 620 m elevation in West Turkana, Kenya was rediscovered after it went missing for more than 30 years. This stranded whale fossil provides the first constraint on the initiation of east African uplift from near sea level at 17 Ma, limiting the timing and initial elevation of environmental change indicated by geodynamic and climatic modeling, paleosols, isotopes, paleobotany, and the mammalian fossil record. At 17 Ma, elevation was low, rainfall was high, vegetation was forested, and mammalian communities contained immigrants and native African species, including diverse primates. Uplift resulted in increasing aridity and open habitats that drove human evolution.
Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making
Authors: Clarke Hannah F. , Horst Nicole K. , Roberts Angela C. 
Published: March 2015

Significance
Fear of negative outcomes has a powerful adverse influence on decision making in anxiety disorders. Although neuroimaging studies of patients with anxiety disorders have revealed dysregulation in numerous frontal brain regions including the orbitofrontal and ventrolateral prefrontal cortex, the causal involvement of this dysregulation is unknown. Here we demonstrate that in the marmoset monkey, inactivation of anterior orbitofrontal or ventrolateral prefrontal cortex increases negative bias in decision making via two distinct cognitive mechanisms—elevated uncertainty and attentional disruption, respectively. These findings provide, to our knowledge, the first direct evidence that dysregulation of distinct neurocognitive mechanisms within the prefrontal cortex may underlie the mixed etiology of anxiety disorders. Such insight will allow the development of more precise diagnostics and individually tailored therapeutic approaches.
Acyl-CoA oxidase complexes control the chemical message produced by
Caenorhabditis elegans
Authors: Zhang Xinxing , Feng Likui , Chinta Satya , Singh Prashant , Wang Yuting , Nunnery Joshawna K. , Butcher Rebecca A. 
Published: March 2015

Significance
Many free-living and parasitic nematode (roundworm) species use pheromones called ascarosides to control their development and behavior. The molecular mechanisms by which environmental factors influence pheromone composition are unknown. The side chains of the ascarosides are derived from long-chain fatty acids that are shortened through β-oxidation cycles. In this manuscript, we show that three acyl-CoA oxidases, which catalyze the first step in the β-oxidation cycles, form specific homo- and heterodimers with different side-chain length preferences. Stressful conditions induce the expression of specific acyl-CoA oxidases, resulting in corresponding changes in pheromone composition. Thus, our work demonstrates how environmental conditions can influence the chemical message that nematodes communicate to other roundworms in the population.
Production and packaging of a biological arsenal: Evolution of centipede venoms under morphological constraint
Authors: Undheim Eivind A. B. , Hamilton Brett R. , Kurniawan Nyoman D. , Bowlay Greg , Cribb Bronwen W. , Merritt David J. , Fry Bryan G. , King Glenn F. , Venter Deon J. 
Published: March 2015

SignificanceVenom peptides have attracted considerable attention because of their value as pharmacological tools and their potential for development as novel pharmaceuticals and bioinsecticides. There is also a growing interest in venoms as model evolutionary systems, particularly for understanding antagonistic coevolutionary processes. We previously demonstrated that although centipede venoms are rich in novel proteins and peptides, there are considerable differences in venom complexity between high-order taxa. We show that this disparity appears to stem from morphological limitations of the venom gland, and that most centipede venoms likely evolve under constraints imposed by low-complexity toxin production facilities. Thus, the centipede venom apparatus should be a useful model system for gaining insight into the impact of morphological constraints on venom evolution.
Genome-wide analysis of thylakoid-bound ribosomes in maize reveals principles of cotranslational targeting to the thylakoid membrane
Authors: Zoschke Reimo , Barkan Alice 
Published: March 2015

Significance
Proteins in the chloroplast thylakoid membrane system are derived from both the nuclear and plastid genomes. Mechanisms that localize nucleus-encoded proteins to the thylakoid membrane have been studied intensively, but little is known about the analogous issues for plastid-encoded proteins. This genome-wide, high-resolution analysis of the partitioning of chloroplast ribosomes between membrane and soluble fractions revealed that approximately half of the chloroplast-encoded thylakoid proteins integrate cotranslationally and half integrate posttranslationally. Features in the nascent peptide that underlie these distinct behaviors were revealed by analysis of the position on each mRNA at which elongating ribosomes first become attached to the membrane.
Soft, curved electrode systems capable of integration on the auricle as a persistent brain–computer interface
Authors: Norton James J. S. , Lee Dong Sup , Lee Jung Woo , Lee Woosik , Kwon Ohjin , Won Phillip , Jung Sung-Young , Cheng Huanyu , Jeong Jae-Woong , Akce Abdullah , Umunna Stephen , Na Ilyoun , Kwon Yong Ho , Wang Xiao-Qi , Liu ZhuangJian , Paik Ungyu , Huang Yonggang , Bretl Timothy , Yeo Woon-Hong , Rogers John A. 
Published: March 2015

Significance
Conventional electroencephalogram (EEG) recording systems, particularly the hardware components that form the physical interfaces to the head, have inherent drawbacks that limit the widespread use of continuous EEG measurements for medical diagnostics, sleep monitoring, and cognitive control. Here we introduce soft electronic constructs designed to intimately conform to the complex surface topology of the auricle and the mastoid, to provide long-term, high-fidelity recording of EEG data. Systematic studies reveal key aspects of the extreme levels of bending and stretching that are involved in mounting on these surfaces. Examples in persistent brain–computer interfaces, including text spellers with steady-state visually evoked potentials and event-related potentials, with viable operation over periods of weeks demonstrate important advances over alternative brain–computer interface technologies.
Silencing of end-joining repair for efficient site-specific gene insertion after TALEN/CRISPR mutagenesis inAedes aegypti
Authors: Basu Sanjay , Aryan Azadeh , Overcash Justin M. , Samuel Glady Hazitha , Anderson Michelle A. E. , Dahlem Timothy J. , Myles Kevin M. , Adelman Zach N. 
Published: March 2015

SignificanceMosquitoes are vectors of both parasites and viruses responsible for high-impact diseases including malaria, dengue, and chikungunya. Novel interventions based on genetic modification of the mosquito genome are currently being developed and implemented. To comprehensively exploit such interventions, detailed knowledge of mosquito physiology, genetics, and genome engineering are required. We developed and validated a two-step process for performing high-efficiency site-specific insertion of genetic material into the mosquito genome by first evaluating candidate site-specific nucleases in a rapid format, followed by germ line-based editing where the choice of DNA repair response is constrained. This model should significantly accelerate both basic and applied research concerning disease vector mosquitoes.