bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation proteomics: A brief overview
Authors: Leszczynski Dariusz
Published: December 2013

Acute biological effects caused by the exposure to high doses of radiation, either ionizing or nonionizing, are relatively well‐known but the delayed effects, occurring decades after exposure, are difficult to predict. The knowledge of the acute and delayed effects of the low doses of ionizing radiation (e.g. bystander effect) or nonionizing radiation (e.g. radiation emitted by wireless communication devices) is not yet reliably established. Often the acute effects of low doses are small and difficult to discover and replicate in scientific studies. Chronic effects of prolonged exposures to low‐dose radiation for decades are virtually unknown and often not possible to predict on the basis of the knowledge gained from acute exposures to high doses of radiation. Physiological significance of the biological effects induced by low doses of radiation is not known. The same lack of predictability of outcomes applies to the delayed effects of high‐dose radiation exposures. Proteomics, supplemented with other “omics” techniques, might be the best way forward to find out the target molecules of radiation, the biomarkers of radiation exposure and the physiological and health significance of the acute and delayed biological effects caused by the exposures to high‐ and low‐dose radiation. However, the currently available database of radiation effects on proteomes is far too small to be useful in formulation of new hypotheses concerning health consequences of radiation exposures.
Immune response to chemically modified proteome
Authors: Bhat Shweta , Mary Sheon , Banarjee Reema , Giri Ashok P. , Kulkarni Mahesh J.
Published: December 2013

Both enzymatic and nonenzymatic PTMs of proteins involve chemical modifications. Some of these modifications are prerequisite for the normal functioning of cell, while other chemical modifications render the proteins as “neo‐self” antigens, which are recognized as “non‐self” leading to aberrant cellular and humoral immune responses. However, these modifications could be a secondary effect of autoimmune diseases, as in the case of type I diabetes, hyperglycemia leads to protein glycation. The enigma of chemical modifications and immune response is akin to the “chick‐and‐egg” paradox. Nevertheless, chemical modifications regulate immune response. In some of the well‐known autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis, chemically modified proteins act as autoantigens forming immune complexes. In some instances, chemical modifications are also involved in regulating immune response during pathogen infection. Further, the usefulness of proteomic analysis of immune complexes is briefly discussed.
Combined exposure to agriculture pesticides, paraquat and maneb, induces alterations in the N/OFQ—NOPr and PDYN/KOPr systems in rats: Relevance to sporadic Parkinson's disease
Authors: Bastías‐Candia Sussy , Di Benedetto Manuela , D'Addario Claudio , Candeletti Sanzio , Romualdi Patrizia
Published: December 2013

Despite several years of research, the aetiology of Parkinson's disease (PD) is quite far from being solved. In PD, as well as in other neurodegenerative disorders, it has been proposed that the combination of multiple factors might contribute to the onset of the disease. Indeed, several authors have suggested that environmental factors, such as pollutants and chemicals, might be associated with the onset of several neurodegenerative disorders. On the other hand, several studies have described that the nociceptin/orphanin‐NOP and prodynorphin‐KOP opioid systems are implicated in the pathology of Parkinson's disease. Considering the nonrestricted commercial availability and common use of several pesticides, such as paraquat and maneb, in agriculture of less developed countries, the aim of our study was to investigate the involvement of nociceptin/orphanin‐NOP and prodynorphin‐KOP systems in a chronic paraquat and maneb animal model of Parkinson's disease. Our results showed that after paraquat/maneb (5/15 mg kg−1) treatment, a significant reduction in tyrosine hydroxylase (TH) levels, the rate‐limiting enzyme for dopamine synthesis, was observed. Also, the association of paraquat and maneb (5/15 mg kg−1) induced an increase in nociceptin/orphanin and a decrease of prodynorphin gene expression levels in the substantia nigra with a down‐regulation of NOP and KOP receptors after both treatments in the substantia nigra and caudate putamen. These data further confirm that paraquat and maneb toxicity can modulate gene expression of the nociceptin/orphanin‐NOP receptor and prodynorphin‐KOP receptor systems in the substantia nigra and caudate putamen, offering further support to the hypothesis that chronic exposure to these agrochemicals might be implicated in the mechanisms underlying sporadic Parkinson's disease. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 656–663, 2015.
Impact of atrial fibrillation on long‐term clinical outcomes in outpatients with heart failure
Authors: Kaneko Hidehiro , Suzuki Shinya , Kano Hiroto , Matsuno Shunsuke , Otsuka Takayuki , Takai Hideaki , Uejima Tokuhisa , Oikawa Yuji , Yajima Junji , Koike Akira , Nagashima Kazuyuki , Kirigaya Hajime , Sagara Koichi , Tanabe Hiroaki , Sawada Hitoshi , Aizawa Tadanori , Yamashita Takeshi
Published: December 2013

Background

Atrial fibrillation (AF) is a common arrhythmia in patients with heart failure (HF); however, its impact on unselected outpatients with HF remains unclear.

Methods

We followed 2024 symptomatic outpatients with HF who visited the Cardiovascular Institute Hospital (The Shinken Database: 2004–2011, N=17,517). We examined the prevalence, clinical characteristics, and outcomes of AF in these outpatients with HF.

Results

AF was observed in 310 of the patients (15%). Patients with AF were older; more likely to be female; and had lower rates of hypertension, diabetes mellitus, and ischemic heart disease. However, they also had higher rates of New York Heart Association grades III/IV, lower left ventricular ejection fraction (EF), renal dysfunction, and dilated cardiomyopathy. The use of cardiovascular drugs including beta‐blockers, renin‐angiotensin‐system inhibitors, diuretics, digitalis, and antiarrhythmic drugs was more common in patients with AF. Kaplan–Meier curves revealed that the incidences of all‐cause death, cardiovascular disease death, and HF‐related admission were significantly higher in patients with AF. Kaplan–Meier curves and an unadjusted Cox regression analysis showed that AF was associated with a significantly higher risk of all‐cause death, cardiovascular death, and HF‐related admission. However, the adjusted Cox regression model showed that AF was no longer an independent risk factor for all‐cause death, cardiovascular death, and HF death but remained an independent risk factor of HF‐related admission (hazard ratio, 1.781; 95% confidence interval, 1.172–2.704; p=0.007).

Conclusions

AF was frequently observed in outpatients with HF. AF was not associated with long‐term mortality but was independently associated with HF‐related admission in this outpatient population.
TLR‐mediated activation of NK cells and their role in bacterial/viral immune responses in mammals
Authors: Adib‐Conquy Minou , Scott‐Algara Daniel , Cavaillon Jean‐Marc , Souza‐Fonseca‐Guimaraes Fernando
Published: December 2013

Natural killer (NK) cells are important in innate immunity, first described as guardians for the detection and clearance of transformed or virus‐infected cells. Later, this cell type was revealed to be also able to recognize and respond to bacteria‐infected cells. NK cells possess receptors allowing them to sense and respond to viral and bacterial patterns, including Toll‐like receptors (TLRs). Initially described in other innate immune cells, particularly monocytes/macrophages, TLRs have more recently been characterized in NK cells. Controversies remain regarding the TLR expression in NK cells and their responsiveness to agonists, specifically the requirement for the presence of accessory cells, such as dendritic cells, or of accessory cytokines (IL‐2, IL‐12, IL‐15 and IL‐18) to respond to TLR agonists. Upon TLR activation, NK cells are an important source of IFN‐γ and granulocyte macrophage colony‐stimulating factor, cytokines necessary to fight infection but that can also contribute to deleterious inflammation if produced in excessive amounts. Here, we review the current knowledge concerning the expression of TLRs in and on NK cells and the responsiveness to their agonists and review the literature on the role of NK cells in the sensing of bacterial or viral patterns and in combatting infection.
Synthesis of metergoline analogues and their evaluation as antiplasmodial agents
Authors: Singh Kawaljit , Kaur Gurminder , Mjambili Faith , Smith Peter J. , Chibale Kelly
Published: December 2013

A series of metergoline analogues were synthesized and evaluatedin vitrofor antiplasmodial activity and cytotoxicity towards a mammalian cell line. Some of the compounds exhibited promising selective antiplasmodial activity along with a high selectivity index relative to metergoline.
Mechanism of water oxidation by nanolayered manganese oxide: a step forward
Authors: Najafpour Mohammad Mahdi , Isaloo Mohsen Abbasi
Published: December 2013

New insights into the mechanism of water oxidation by layered Mn oxide are reported.
Installation and commissioning of the new Fermi National Accelerator Laboratory H- Magnetron
Authors: Bollinger D. S.
Published: December 2013

The Fermi National Accelerator Laboratory (FNAL) 40 year old Cockcroft-Walton 750 keV injectors with slit aperture magnetron ion sources have been replaced with a circular aperture magnetron, Low Energy Beam Transport, Radio Frequency Quadrupole Accelerator, and Medium Energy Beam Transport, as part of the FNAL Proton Improvement Plan. The injector design is based on a similar system at Brookhaven National Laboratory. The installation, commissioning efforts, and source operations to date will be covered in this paper along with plans for additional changes to the original design to improve reliability by reducing extractor spark rates and arc current duty factor.
Spatial spectrograms of vibrating atomic force microscopy cantilevers coupled to sample surfaces
Authors: Wagner Ryan , Raman Arvind , Proksch Roger
Published: December 2013

Many advanced dynamic Atomic Force Microscopy (AFM) techniques such as contact resonance, force modulation, piezoresponse force microscopy, electrochemical strain microscopy, and AFM infrared spectroscopy exploit the dynamic response of a cantilever in contact with a sample to extract local material properties. Achieving quantitative results in these techniques usually requires the assumption of a certain shape of cantilever vibration. We present a technique that allows in-situ measurements of the vibrational shape of AFM cantilevers coupled to surfaces. This technique opens up unique approaches to nanoscale material property mapping, which are not possible with single point measurements alone.
An interferometric scanning microwave microscope and calibration method for sub-fF microwave measurements
Authors: Dargent T. , Haddadi K. , Lasri T. , Clément N. , Ducatteau D. , Legrand B. , Tanbakuchi H. , Theron D.
Published: December 2013

We report on an adjustable interferometric set-up for Scanning Microwave Microscopy. This interferometer is designed in order to combine simplicity, a relatively flexible choice of the frequency of interference used for measurements as well as the choice of impedances range where the interference occurs. A vectorial calibration method based on a modified 1-port error model is also proposed. Calibrated measurements of capacitors have been obtained around the test frequency of 3.5 GHz down to about 0.1 fF. Comparison with standard vector network analyzer measurements is shown to assess the performance of the proposed system.
Field-dependent critical state of high-Tc superconducting strip simultaneously exposed to transport current and perpendicular magnetic field
Authors: Xue Cun , He An , Yong Huadong , Zhou Youhe
Published: December 2013

We present an exact analytical approach for arbitrary field-dependent critical state of high-Tc superconducting strip with transport current. The sheet current and flux-density profiles are derived by solving the integral equations, which agree with experiments quite well. For small transport current, the approximate explicit expressions of sheet current, flux-density and penetration depth for the Kim model are derived based on the mean value theorem for integration. We also extend the results to the field-dependent critical state of superconducting strip in the simultaneous presence of applied field and transport current. The sheet current distributions calculated by the Kim model agree with experiments better than that by the Bean model. Moreover, the lines in the Ia-Ba plane for the Kim model are not monotonic, which is quite different from that the Bean model. The results reveal that the maximum transport current in thin superconducting strip will decrease with increasing applied field which vanishes for the Bean model. The results of this paper are useful to calculate ac susceptibility and ac loss.
Possibility of perfect concealment by lossy conventional and lossy metamaterial cylindrical invisibility cloaks
Authors: Dehbashi Reza , Shahabadi Mahmoud
Published: December 2013

The commonly used coordinate transformation for cylindrical cloaks is generalized. This transformation is utilized to determine an anisotropic inhomogeneous diagonal material tensors of a shell type cloak for various material types, i.e., double-positive (DPS: ε, μ > 0), double-negative (DNG: ε, μ < 0), ε-negative (ENG), and μ-negative (MNG). To obtain conditions of perfect cloaking for various material types, a rigorous analysis is performed. It is shown that perfect cloaking will be achieved for same type material for the cloak and its surrounding medium. Moreover, material losses are included in the analysis to demonstrate that perfect cloaking for lossy materials can be achieved for identical loss tangent of the cloak and its surrounding material. Sensitivity of the cloaking performance to losses for different material types is also investigated. The obtained analytical results are verified using a Finite-Element computational analysis.
Near-infrared optical parametric oscillator in a III-V semiconductor waveguide
Authors: Savanier M. , Ozanam C. , Lanco L. , Lafosse X. , Andronico A. , Favero I. , Ducci S. , Leo G.
Published: December 2013

We demonstrate a near-infrared integrated optical parametric oscillator (OPO) in a direct gap semiconductor. Based on a selectively oxidized GaAs/AlGaAs waveguide and monolithic SiO2/TiO2 dichroic Bragg mirrors, this device combines a strong non-resonant quadratic nonlinearity and form-birefringent type-I phase matching. With a TM00 pump around 1 μm and TE00 signal and idler around 2 μm in a single-pass-pump doubly resonant scheme, we observe an oscillation threshold of 210 mW at degeneracy in the continuous-wave regime. This result represents a significant milestone in the perspective of an electrically injected OPO on chip.
Cyclotron resonance in plasma flow
Authors: Artemyev A. V. , Agapitov O. V. , Krasnoselskikh V. V.
Published: December 2013

This paper is devoted to the mechanism of particle acceleration via resonant interaction with the electromagnetic circular wave propagating along the inhomogeneous background magnetic field in the presence of a plasma flow. We consider the system where the plasma flow velocity is large enough to change the direction of wave propagation in the rest frame. This system mimics a magnetic field configuration typical for inner structure of a quasi-parallel shock wave. We consider conditions of gyroresonant interaction when the force corresponding to an inhomogeneity of the background magnetic field is compensated by the Lorentz force of the wave-magnetic field. The wave-amplitude is assumed to be about 10% of the background magnetic field. We show that particles can gain energy if kvsw>ω>kvsw−Ωc where k is the wave number, vsw is a plasma flow velocity, and ω and Ωc are the wave frequency and the particle gyrofrequency, respectively. This mechanism of acceleration resembles the gyrosurfing mechanism, but the effect of the electrostatic field is replaced by the effect of the magnetic field inhomogeneity.
Artificial neural network based prediction model of daily global solar radiation in Morocco
Authors: Mejdoul R. , Taqi M. , Belouaggadia N.
Published: December 2013

In this study, an artificial neural network (ANN) daily global solar radiation (DGSR) predicting model was developed. In addition to geographical coordinates and the Julian day number, the inputs include six atmosphere physical parameters: maximal and minimal daily temperature, maximal and minimal daily humidity, daily total column of evaporating water and sunshine duration. The only output of the model is the DGSR. The used data is from eight weather stations spread out on different climate Moroccan regions, 80% of this data is chosen randomly to train the ANN while the remaining was used for the testing and validating phases. Several training algorithms are tested to minimize the sum of square error between the target and output and many combinations of the input parameters are tested to reduce their number. It is found that the ANN trained by The Broyden-Fletcher-Goldfarb-Shanno algorithm gives 0.98 as correlation, 1% as mean absolute percentage error and 1.2 MJ/m2/day as root mean square error both in training and validating phases. The trained and validated results of this model show a great accuracy either for estimating the DGSR in Moroccan regions where this parameter lack or for forecasting it in modeling process.
Effect of substrate temperature on the magnetic properties of epitaxial sputter-grown Co/Pt
Authors: Mihai A. P. , Whiteside A. L. , Canwell E. J. , Marrows C. H. , Benitez M. J. , McGrouther D. , McVitie S. , McFadzean S. , Moore T. A.
Published: December 2013

Epitaxial Co/Pt films have been deposited by dc-magnetron sputtering onto heated C-plane sapphire substrates. X-ray diffraction, the residual resistivity, and transmission electron microscopy indicate that the Co/Pt films are highly ordered on the atomic scale. The coercive field and the perpendicular magnetic anisotropy increase as the substrate temperature is increased from 100–250 °C during deposition of the Co/Pt. Measurement of the domain wall creep velocity as a function of applied magnetic field yields the domain wall pinning energy, which scales with the coercive field. Evidence for an enhanced creep velocity in highly ordered epitaxial Co/Pt is found.
Quantum efficiency affected by localized carrier distribution near the V-defect in GaN based quantum well
Authors: Cho Yong-Hee , Kim Jun-Youn , Kim Jaekyun , Shim Mun-Bo , Hwang Sangheum , Park Seoung-Hwan , Park Young-Soo , Kim Sungjin
Published: December 2013

It is known that due to the formation of in-plane local energy barrier, V-defects can screen the carriers which non-radiatively recombine in threading dislocations (TDs) and hence, enhance the internal quantum efficiency in GaN based light-emitting diodes. By a theoretical modeling capable of describing the inhomogeneous carrier distribution near the V-defect in GaN based quantum wells, we show that the efficient suppression of non-radiative (NR) recombination via TD requires the local energy barrier height of V-defect larger than ∼80 meV. The NR process in TD combined with V-defect influences the quantum efficiency mainly in the low injection current density regime suitably described by the linear dependence of carrier density. We provide a simple phenomenological expression for the NR recombination rate based on the model result.
Deposition of thin silicon layers on transferred large area graphene
Authors: Lupina Grzegorz , Kitzmann Julia , Lukosius Mindaugas , Dabrowski Jarek , Wolff Andre , Mehr Wolfgang
Published: December 2013

Physical vapor deposition of Si onto transferred graphene is investigated. At elevated temperatures, Si nucleates preferably on wrinkles and multilayer graphene islands. In some cases, however, Si can be quasi-selectively grown only on the monolayer graphene regions while the multilayer islands remain uncovered. Experimental insights and ab initio calculations show that variations in the removal efficiency of carbon residuals after the transfer process can be responsible for this behavior. Low-temperature Si seed layer results in improved wetting and enables homogeneous growth. This is an important step towards realization of electronic devices in which graphene is embedded between two Si layers.
Excitonic enhancement of nonradiative energy transfer to bulk silicon with the hybridization of cascaded quantum dots
Authors: Yeltik Aydan , Guzelturk Burak , Ludwig Hernandez-Martinez Pedro , Akhavan Shahab , Volkan Demir Hilmi
Published: December 2013

We report enhanced sensitization of silicon through nonradiative energy transfer (NRET) of the excitons in an energy-gradient structure composed of a cascaded bilayer of green- and red-emitting CdTe quantum dots (QDs) on bulk silicon. Here NRET dynamics were systematically investigated comparatively for the cascaded energy-gradient and mono-dispersed QD structures at room temperature. We show experimentally that NRET from the QD layer into silicon is enhanced by 40% in the case of an energy-gradient cascaded structure as compared to the mono-dispersed structures, which is in agreement with the theoretical analysis based on the excited state population-depopulation dynamics of the QDs.
Direct and quantitative photothermal absorption spectroscopy of individual particulates
Authors: Tong Jonathan K. , Hsu Wei-Chun , Eon Han Sang , Burg Brian R. , Zheng Ruiting , Shen Sheng , Chen Gang
Published: December 2013

Photonic structures can exhibit significant absorption enhancement when an object's length scale is comparable to or smaller than the wavelength of light. This property has enabled photonic structures to be an integral component in many applications such as solar cells, light emitting diodes, and photothermal therapy. To characterize this enhancement at the single particulate level, conventional methods have consisted of indirect or qualitative approaches which are often limited to certain sample types. To overcome these limitations, we used a bilayer cantilever to directly and quantitatively measure the spectral absorption efficiency of a single silicon microwire in the visible wavelength range. We demonstrate an absorption enhancement on a per unit volume basis compared to a thin film, which shows good agreement with Mie theory calculations. This approach offers a quantitative approach for broadband absorption measurements on a wide range of photonic structures of different geometric and material compositions.
Synthesis of Fluorinated Aromatic Compounds by One-Pot Benzyne Generation and Nucleophilic Fluorination
Authors: Ikawa Takashi , Masuda Shigeaki , Nishiyama Tsuyoshi , Takagi Akira , Akai Shuji
Published: December 2013

The fluorination of substituted benzenes using fluoride ions under mild reaction conditions has been one of the most important challenges for the synthesis of biologically active fluorinated aromatic compounds; however, only a few synthetically useful methods are known. In this paper, it is reported that the nucleophilic fluorination of benzynes, generated from either 2-(trialkylsilyl)phenyl nonafluorobutanesulfonates or 2-(trialkylsilyl)phenols, meets this challenge. In particular, the fluorination starting from 2-(trialkylsilyl)phenols for fabricating aryl fluorides involves three sequential reactions in one-pot: the nonaflylation of phenols, benzyne generation, and nucleophilic fluorination of the benzynes. The regioselectivities of these reactions are controlled by the substituents at the C3-position of the benzynes.
Regulation of PTEN inhibition by the pleckstrin homology domain of P-REX2 during insulin signaling and glucose homeostasis
Authors: Hodakoski Cindy , Hopkins Benjamin D. , Barrows Douglas , Mense Sarah M. , Keniry Megan , Anderson Karen E. , Kern Philip A. , Hawkins Phillip T. , Stephens Len R. , Parsons Ramon
Published: December 2013

Significance

Proper insulin signaling is necessary for regulating glucose metabolism and is often deregulated in cancer. Insulin activation of the phosphoinositide-3 kinase (PI3K) pathway is negatively regulated by the tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN). We previously described a novel inhibitor of PTEN activity, phosphatidylinositol 3,4,5-trisphosphate-dependent Rac exchanger 2 (P-REX2). Here, we show that P-REX2 inhibition of PTEN occurs through the pleckstrin homology (PH) domain and requires PTEN C-terminal tail phosphorylation. Furthermore, loss of
Prex2
results in reduced insulin signaling and increased Pten activity, and mice lacking P-rex2 display impaired glucose uptake and insulin resistance. This reveals a crucial role for the PH domain of P-REX2 in the regulation of glucose metabolism through the inhibition of PTEN.
Aphid amino acid transporter regulates glutamine supply to intracellular bacterial symbionts
Authors: Price Daniel R. G. , Feng Honglin , Baker James D. , Bavan Selvan , Luetje Charles W. , Wilson Alex C. C.
Published: December 2013

Significance

Nutritional bacterial endosymbionts are housed in specialized host cells and are partitioned from the host cell cytoplasm by a host-derived symbiosomal membrane. This cellular organization isolates bacterial symbionts from nutrient pools in the host cell and makes possible host control of nutrient supply to bacterial symbionts. Here, using the aphid–
Buchnera
nutritional endosymbiosis, we demonstrate that the most active host glutamine (precursor) transporter,
Acyrthosiphon pisum
glutamine transporter 1, is competitively inhibited by arginine (a
Buchnera
-synthesized end product). We propose a model of endosymbiosis regulation in which precursor transport is regulated by a symbiont-synthesized end product. Thus, we provide insights into the molecular mechanism of host control of bacterial endosymbiont essential nutrient biosynthesis.
Secular chaos and its application to Mercury, hot Jupiters, and the organization of planetary systems
Authors: Lithwick Yoram , Wu Yanqin
Published: December 2013

Significance

Planets perturb one another as they orbit their star. These perturbations can build up over a long time, leading to instability and chaos, and, ultimately, to dramatic events such as interplanetary collisions. We focus here on “secular chaos,” which is the chaos that arises in the orbit-averaged equations. We explain how secular chaos works and show that it explains the chaos of Mercury's orbit. We also show that secular chaos could be responsible for the formation of “hot Jupiters,” which are Jupiter-mass planets that orbit very close to their star. Finally, we suggest that secular chaos might be important not only for Mercury and hot Jupiters, but also more generally for organizing a wide variety of extrasolar planetary systems.
Structural and biochemical basis for the inhibition of cell death by APIP, a methionine salvage enzyme
Authors: Kang Wonchull , Hong Se Hoon , Lee Hye Min , Kim Na Yeon , Lim Yun Chan , Le Le Thi My , Lim Bitna , Kim Hyun Chul , Kim Tae Yeon , Ashida Hiroki , Yokota Akiho , Hah Sang Soo , Chun Keun Ho , Jung Yong-Keun , Yang Jin Kuk
Published: December 2013

Significance

Apaf-1 interacting protein (APIP) inhibits two main types of programmed cell death: apoptosis and pyroptosis. In addition, APIP is a 5-methylthioribulose-1-phosphate dehydratase (MtnB) in the methionine salvage pathway. We verified its enzymatic activity directly through an enzyme assay and determined its high-resolution structure. Furthermore, we explored the relationship between two distinct functions of APIP/MtnB, cell death inhibition and methionine salvage, and determined that it functions as a cell death inhibitor independently of its MtnB enzyme activity for apoptosis, but dependently for caspase-1–induced pyroptosis. Our results provide groundwork for studies of the role of APIP/MtnB in development of cancers and inflammatory diseases.
Pch2 is a hexameric ring ATPase that remodels the chromosome axis protein Hop1
Authors: Chen Cheng , Jomaa Ahmad , Ortega Joaquin , Alani Eric E.
Published: December 2013

Significance

The conserved
PCH2
gene in baker’s yeast regulates meiotic double-strand break repair outcomes, helps establish a proper meiotic chromosome structure, and is important for the progression of meiotic recombination. Its mouse homolog is required for fertility. However, the molecular mechanism of how
PCH2
regulates these diverse functions is not known. In this study, we show that Pch2 is an AAA
+
family ATPase (ATPases associated with diverse cellular activities) that oligomerizes into single hexameric rings. In the presence of ATP, Pch2 binds to and remodels Hop1, an important component of the synaptonemal complex, and displaces it from DNA. Based on these and previous observations, we suggest that Pch2 impacts meiotic chromosome organization by directly regulating Hop1 binding to DNA.
Mathematical modeling of primary succession of murine intestinal microbiota
Authors: Marino Simeone , Baxter Nielson T. , Huffnagle Gary B. , Petrosino Joseph F. , Schloss Patrick D.
Published: December 2013

Significance

The colonization of the intestinal track by the trillions of bacteria that live in the gut (i.e., the gut microbiome) is a dynamic process. Through the use of next-generation sequencing and mathematical models, we were able to quantify the interpopulation interactions that occurred after a germfree mouse was inoculated with a murine microbiome. This approach was significant because we were able to quantify these interactions in vivo without the use of cultivation. Although colonization is most commonly associated with the development of a neonate’s microbiome, understanding the ecological mechanisms involved in the successional process is critical to understanding the recovery of the microbiome following antibiotic therapies, changes in diet, and shifts in health.
Ghrelin triggers the synaptic incorporation of AMPA receptors in the hippocampus
Authors: Ribeiro Luís F. , Catarino Tatiana , Santos Sandra D. , Benoist Marion , van Leeuwen J. Fiona , Esteban José A. , Carvalho Ana Luísa
Published: December 2013

Significance

Ghrelin is a peptide released from the empty stomach into circulation, and which acts on the brain to promote appetite. Recent studies showed that ghrelin also affects cognition, but the mechanism for this effect is unknown. We show that activation of ghrelin receptors in the hippocampus enhances synaptic signaling by glutamate, the major excitatory neurotransmitter in the brain. Ghrelin promotes the synaptic accumulation of glutamate receptors of the AMPA subtype, and increases long-term potentiation, one form of synaptic plasticity that is thought to underlie learning and memory. These molecular effects of ghrelin in the hippocampus may contribute to the cognition-enhancing role of ghrelin.
Direct observation of a transient ternary complex during IκBα-mediated dissociation of NF-κB from DNA
Authors: Alverdi Vera , Hetrick Byron , Joseph Simpson , Komives Elizabeth A.
Published: December 2013

Significance

The nuclear factor kappa B (NF-κB) family of transcription factors regulates hundreds of genes in response to stress. Stress responses must be robust when needed and then completely and rapidly turned off. A family of inhibitor proteins, the IκBs, is responsible for turning off NF-κBs. Our study shows that IκBα turns off NF-κB(RelA/p50) by rapidly binding to the DNA-bound NF-κB, forming a transient ternary complex. The ternary complex lasts for only milliseconds before the DNA dissociates from the complex. The resulting IκBα–NF-κB complex is extremely stable and cannot be dissociated. Our study shows how the macromolecular interactions of IκBα are precisely tuned to efficiently and irreversibly turn off NF-κB transcriptional activity.
Seasonal ITCZ migration dynamically controls the location of the (sub)tropical Atlantic biogeochemical divide
Authors: Schlosser Christian , Klar Jessica K. , Wake Bronwyn D. , Snow Joseph T. , Honey David J. , Woodward E. Malcolm S. , Lohan Maeve C. , Achterberg Eric P. , Moore C. Mark
Published: December 2013

Significance

Low concentrations of fixed nitrogen restrict phytoplankton growth in much of the low-latitude surface oceans. Diazotrophic cyanobacteria are capable of fixing atmospheric dinitrogen, thereby replenishing the overall pool of fixed nitrogen. As a consequence, spatial–temporal variability in diazotrophy can potentially influence the global nitrogen cycle. Here we show that movement in the region of elevated iron concentrations tied to the seasonal migration of the intertropical convergence zone drives a shift in the latitudinal distribution of dinitrogen fixation and corresponding phosphate depletion in surface waters. Surface nutrient concentrations and diazotrophic activity divide the (sub)tropical Atlantic into a high-phosphate, low-iron system in the south, and a low-phosphate, high-iron system in the north.
Dynamic pricing of network goods with boundedly rational consumers
Authors: Radner Roy , Radunskaya Ami , Sundararajan Arun
Published: December 2013

Significance

A consumer’s demand for a network good depends on the demands of other consumers, and therefore choosing this demand optimally poses a cognitive challenge for most consumers. In our model of pricing a network good, consumers display “bounded rationality” (in Herbert Simon’s sense), and the vendor chooses a dynamic price path to maximize the present value of profit. The result is a price and quantity path that differs significantly from that predicted by standard economic theory and is closer to empirical observations.
Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination
Authors: Furman David , Hejblum Boris P. , Simon Noah , Jojic Vladimir , Dekker Cornelia L. , Thiébaut Rodolphe , Tibshirani Robert J. , Davis Mark M.
Published: December 2013

Significance

There are marked differences between the sexes in their immune response to infections and vaccination, with females often having significantly higher responses. However, the mechanisms underlying these differences are largely not understood. Using a systems immunology approach, we have identified a cluster of genes involved in lipid metabolism and likely modulated by testosterone that correlates with the higher antibody-neutralizing response to influenza vaccination observed in females. Moreover, males with the highest testosterone levels and expression of related gene signatures exhibited the lowest antibody responses to influenza vaccination. This study generates a number of hypotheses on the sex differences observed in the human immune system and their relationship to mechanisms involved in the antibody response to vaccination.
Neisseria meningitidis
NalP cleaves human complement C3, facilitating degradation of C3b and survival in human serum
Authors: Del Tordello Elena , Vacca Irene , Ram Sanjay , Rappuoli Rino , Serruto Davide
Published: December 2013

Significance

The complement system is a crucial component of the innate immune response in humans. In this study, we report the characterization of an autotransporter protease of
Neisseria meningitidis
named NalP. We show that NalP is able to cleave the α-chain of the human complement factor C3 in a species-specific manner. As a consequence, the deposition of C3b on the bacterial surface is reduced and, in human serum, the NalP-generated C3b fragment is further degraded by host factors. Our results significantly increase the knowledge of how
N. meningitidis
can survive and multiply in human serum, evading the innate immune system.
BK channel opening involves side-chain reorientation of multiple deep-pore residues
Authors: Chen Xixi , Yan Jiusheng , Aldrich Richard W.
Published: December 2013

Significance

The BK calcium-activated potassium channels are important regulators of electrical and calcium signaling in many types of tissue. BK channel activation involves complex conformational changes. We investigated the molecular details of such conformational changes with scanning mutagenesis and electrophysiological measurements. We found multiple pore residues that reorient their side chains during channel opening. These findings bridge the gap between our knowledge about the static X-ray structure of ion channel pores and knowledge about their functional dynamics.
Designed amyloid fibers as materials for selective carbon dioxide capture
Authors: Li Dan , Furukawa Hiroyasu , Deng Hexiang , Liu Cong , Yaghi Omar M. , Eisenberg David S.
Published: December 2013

Significance

New and improved materials capable of binding carbon dioxide are essential to addressing the global threat of accelerating climate change. The presently used industrial methods for carbon dioxide capture have severe drawbacks, including toxicity and energy inefficiency. Newer porous materials are so far less effective in water, invariably a component of combustion gases. Here, we present a material for carbon dioxide capture. This material, amyloid fibers in powdered form, selectively captures carbon dioxide in the presence of water and binds carbon dioxide strongly until it is released by heating, regenerating the robust amyloid fibers in an energy efficient process.
Acyl-CoA synthetase 3 promotes lipid droplet biogenesis in ER microdomains
Authors: Kassan Adam , Herms Albert , Fernández-Vidal Andrea , Bosch Marta , Schieber Nicole L. , Reddy Babu J.N. , Fajardo Alba , Gelabert-Baldrich Mariona , Tebar Francesc , Enrich Carlos , Gross Steven P. , Parton Robert G. , Pol Albert
Published: December 2013

Control of lipid droplet (LD) nucleation and copy number are critical, yet poorly understood, processes. We use model peptides that shift from the endoplasmic reticulum (ER) to LDs in response to fatty acids to characterize the initial steps of LD formation occurring in lipid-starved cells. Initially, arriving lipids are rapidly packed in LDs that are resistant to starvation (pre-LDs). Pre-LDs are restricted ER microdomains with a stable core of neutral lipids. Subsequently, a first round of “emerging” LDs is nucleated, providing additional lipid storage capacity. Finally, in proportion to lipid concentration, new rounds of LDs progressively assemble. Confocal microscopy and electron tomography suggest that emerging LDs are nucleated in a limited number of ER microdomains after a synchronized stepwise process of protein gathering, lipid packaging, and recognition by Plin3 and Plin2. A comparative analysis demonstrates that the acyl-CoA synthetase 3 is recruited early to the assembly sites, where it is required for efficient LD nucleation and lipid storage.
Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation
Authors: Goenka Radhika , Matthews Andrew H. , Zhang Bochao , O’Neill Patrick J. , Scholz Jean L. , Migone Thi-Sau , Leonard Warren J. , Stohl William , Hershberg Uri , Cancro Michael P.
Published: December 2013

We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21–mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell–derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence.
Impact of Medicare's Payment Policy on Mediastinitis Following Coronary Artery Bypass Graft Surgery in US Hospitals
Authors: Calderwood Michael S. , Kleinman Ken , Soumerai Stephen B. , Jin Robert , Gay Charlene , Piatt Richard , Kassler William , Goldmann Donald A. , Jha Ashish K. , Lee Grace M.
Published: December 2013

Background.

The Centers for Medicare and Medicaid Services (CMS) implemented a policy in October 2008 to eliminate additional Medicare payment for mediastinitis following coronary artery bypass graft (CABG) surgery.

Objective.

To evaluate the impact of this policy on mediastinitis rates, using Medicare claims and National Healthcare Safety Network (NHSN) prospective surveillance data.

Methods.

We used an interrupted time series design to compare mediastinitis rates before and after the policy, adjusted for secular trends. Billing rates came from Medicare inpatient claims following 638,761 CABG procedures in 1,234 US hospitals (January 2006-September 2010). Prospective surveillance rates came from 151 NHSN hospitals in 29 states performing 94,739 CABG procedures (January 2007-September 2010). Logistic regression mixed-effects models estimated trends for mediastinitis rates.

Results.

We found a sudden drop in coding for index admission mediastinitis at the time of policy implementation (odds ratio, 0.36 [95% confidence interval (CI), 0.23-0.57]) and a decreasing trend in coding for index admission mediastinitis in the postintervention period compared with the preintervention period (ratio of slopes, 0.83 [95% CI, 0.74-0.95]). However, we saw no impact of the policy on infection rates as measured using NHSN data. Our results were not affected by changes in patient risk over time, heterogeneity in hospital demographics, or timing of hospital participation in NHSN.

Conclusions.

The CMS policy of withholding additional Medicare payment for mediastinitis on the basis of claims-based evidence of infection was associated with changes in coding for infections but not with changes in actual infection rates during the first 2 years after policy implementation.
CCAT: Combinatorial Code Analysis Tool for transcriptional regulation
Authors: Jiang Peng , Singh Mona
Published: December 2013

Combinatorial interplay among transcription factors (TFs) is an important mechanism by which transcriptional regulatory specificity is achieved. However, despite the increasing number of TFs for which either binding specificities or genome-wide occupancy data are known, knowledge about cooperativity between TFs remains limited. To address this, we developed a computational framework for predicting genome-wide co-binding between TFs (CCAT, Combinatorial Code Analysis Tool), and applied it to Drosophila melanogaster to uncover cooperativity among TFs during embryo development. Using publicly available TF binding specificity data and DNaseI chromatin accessibility data, we first predicted genome-wide binding sites for 324 TFs across five stages of D. melanogaster embryo development. We then applied CCAT in each of these developmental stages, and identified from 19 to 58 pairs of TFs in each stage whose predicted binding sites are significantly co-localized. We found that nearby binding sites for pairs of TFs predicted to cooperate were enriched in regions bound in relevant ChIP experiments, and were more evolutionarily conserved than other pairs. Further, we found that TFs tend to be co-localized with other TFs in a dynamic manner across developmental stages. All generated data as well as source code for our front-to-end pipeline are available at http://cat.princeton.edu.
Weighted cue integration in the rodent head direction system
Authors: Knight Rebecca , Piette Caitlin E. , Page Hector , Walters Daniel , Marozzi Elizabeth , Nardini Marko , Stringer Simon , Jeffery Kathryn J.
Published: December 2013

How the brain combines information from different sensory modalities and of differing reliability is an important and still-unanswered question. Using the head direction (HD) system as a model, we explored the resolution of conflicts between landmarks and background cues. Sensory cue integration models predict averaging of the two cues, whereas attractor models predict capture of the signal by the dominant cue. We found that a visual landmark mostly captured the HD signal at low conflicts: however, there was an increasing propensity for the cells to integrate the cues thereafter. A large conflict presented to naive rats resulted in greater visual cue capture (less integration) than in experienced rats, revealing an effect of experience. We propose that weighted cue integration in HD cells arises from dynamic plasticity of the feed-forward inputs to the network, causing within-trial spatial redistribution of the visual inputs onto the ring. This suggests that an attractor network can implement decision processes about cue reliability using simple architecture and learning rules, thus providing a potential neural substrate for weighted cue integration.
Architecture of spatial circuits in the hippocampal region
Authors: Witter Menno P. , Canto Cathrin B. , Couey Jonathan J. , Koganezawa Noriko , O'Reilly Kally C.
Published: December 2013

The hippocampal region contains several principal neuron types, some of which show distinct spatial firing patterns. The region is also known for its diversity in neural circuits and many have attempted to causally relate network architecture within and between these unique circuits to functional outcome. Still, much is unknown about the mechanisms or network properties by which the functionally specific spatial firing profiles of neurons are generated, let alone how they are integrated into a coherently functioning meta-network. In this review, we explore the architecture of local networks and address how they may interact within the context of an overarching space circuit, aiming to provide directions for future successful explorations.
Functional connectivity of the entorhinal–hippocampal space circuit
Authors: Zhang Sheng-Jia , Ye Jing , Couey Jonathan J. , Witter Menno , Moser Edvard I. , Moser May-Britt
Published: December 2013

The mammalian space circuit is known to contain several functionally specialized cell types, such as place cells in the hippocampus and grid cells, head-direction cells and border cells in the medial entorhinal cortex (MEC). The interaction between the entorhinal and hippocampal spatial representations is poorly understood, however. We have developed an optogenetic strategy to identify functionally defined cell types in the MEC that project directly to the hippocampus. By expressing channelrhodopsin-2 (ChR2) selectively in the hippocampus-projecting subset of entorhinal projection neurons, we were able to use light-evoked discharge as an instrument to determine whether specific entorhinal cell groups—such as grid cells, border cells and head-direction cells—have direct hippocampal projections. Photoinduced firing was observed at fixed minimal latencies in all functional cell categories, with grid cells as the most abundant hippocampus-projecting spatial cell type. We discuss how photoexcitation experiments can be used to distinguish the subset of hippocampus-projecting entorhinal neurons from neurons that are activated indirectly through the network. The functional breadth of entorhinal input implied by this analysis opens up the potential for rich dynamic interactions between place cells in the hippocampus and different functional cell types in the entorhinal cortex (EC).