bluuebunny/crossref_metadata_2025_split huggingface dataset:
New Approaches to Neuroprotection in Parkinson’s Disease
Authors: Mena María Angeles , Perucho Juan , López-Sendón José Luis , Yébenes Justo García de 
Published: September 2013

Parkinson's disease (PD) is a neurodegenerative disorder characterized by akinesia, rigidity, tremor at rest and postural abnormalities, as well as other symptoms involving the central and the autonomic nervous system. PD affects up to 300 patients per 100 000 inhabitants with a higher prevalence in males. The neuropathological features of PD include a severe neuronal loss in the dopamine-rich substantia nigra and other monoamine rich brain stem nuclei, and a severe loss of striatal levels of dopamine and its metabolites. The vast majority of patients with PD show intraneuronal inclusion bodies immunoreactive to α-synuclein in their nigrostriatal dopamine cells, as well as in neurons of other nuclei from the central and autonomic nervous system.
The treatment of PD is one of the greatest successes in the history of medicine, since in the last half century a large number of pharmaceutical compounds, and surgical intervention, have completely changed the prognosis of this disease. These treatments have returned patients with PD to a normal life expectancy and allow for a good quality of life for many years after diagnosis. The treatments available, however, do not stop the progression of the disease and most patients surviving for long periods of time after the initiation of therapy develop complications such as fluctuations, dyskinesias, disturbances related to lack of control of impulses and several types of cognitive deterioration.
Neuroprotection in PD is difficult since this disease involves multiple different pathogenic mechanisms interacting with the patient's own process of aging. Mendelian genetic mechanisms causing PD include more than 16 canonical gene defects plus an increasing number of genetic risk factors. These molecular abnormalities responsible for PD include abnormalities of neurotransmitter metabolism, excessive free radicals, abnormal mitochondrial function, excessive accumulation of denatured proteins, abnormalities of kinases and others. Strategies for neuroprotection need to take into consideration the enormous variety of pathogenic mechanisms, and the need to design specific therapies for the specific molecular defects present in each case.
A comprehensive analysis of oxidative stress in the ozone-induced lung inflammation mouse model
Authors: Wiegman Coen H. , Li Feng , Clarke Colin J. , Jazrawi Elen , Kirkham Paul , Barnes Peter J. , Adcock Ian M. , Chung Kian F. 
Published: September 2013

Ozone is an oxidizing environmental pollutant that contributes significantly to respiratory health. Exposure to increased levels of ozone has been associated with worsening of symptoms of patients with asthma and COPD (chronic obstructive pulmonary disease). In the present study, we investigated the acute and chronic effects of ozone exposure-induced oxidative stress-related inflammation mechanics in mouse lung. In particular, we investigated the oxidative stress-induced effects on HDAC2 (histone deacetylase 2) modification and activation of the Nrf2 (nuclear factor erythroid-related factor 2) and HIF-1α (hypoxia-inducible factor-1α) signalling pathways. Male C57BL/6 mice were exposed to ozone (3 p.p.m.) for 3 h a day, twice a week for a period of 1, 3 or 6 weeks. Control mice were exposed to normal air. After the last exposure, mice were killed for BAL (bronchoalveolar lavage) fluid and lung tissue collection. BAL total cell counts were elevated at all of the time points studied. This was associated with increased levels of chemokines and cytokines in all ozone-exposed groups, indicating the presence of a persistent inflammatory environment in the lung. Increased inflammation and Lm (mean linear intercept) scores were observed in chronic exposed mice, indicating emphysematous changes were present in lungs of chronic exposed mice. The antioxidative stress response was active (indicated by increased Nrf2 activity and protein) after 1 week of ozone exposure, but this ability was lost after 3 and 6 weeks of ozone exposure. The transcription factor HIF-1α was elevated in 3- and 6-week ozone-exposed mice and this was associated with increased gene expression levels of several HIF-1α target genes including Hdac2 (histone deacetylase 2), Vegf (vascular endothelial growth factor), Keap1 (kelch-like ECH-associated protein 1) and Mif (macrophage migration inhibitory factor). HDAC2 protein was found to be phosphorylated and carbonylated in nuclear and cytoplasm fractions, respectively, and was associated with a decrease in DNA-binding activity and protein expression of HDAC2. Decreased HDAC2 activity, most likely a direct result of protein modification, in combination with the loss of the antioxidative stress response and activation of the HIF-1α pathway, contribute to the inflammatory response and emphysema observed in ozone-exposed mice.
Photochemical doping of graphene oxide with nitrogen for photoluminescence enhancement
Authors: Liu Fuchi , Tang Nujiang , Tang Tao , Liu Yuan , Feng Qian , Zhong Wei , Du Youwei 
Published: September 2013

Nitrogen-doped graphene oxide (NGO) was synthesized by irradiation of graphene oxide (GO) in NH3 atmosphere. NGO obtained by irradiation of GO for 10 min has high N content of 13.62 at. %. The photoluminescence (PL) properties of NGO were investigated. The results showed that compared with GO, NGO exhibits significant PL enhancement with a high enhancement ratio of approximately 1501.57%. It may attribute to the high content of amino-like N, which can effectively enhance PL of GO because of the amino conjugation effect.
NFAT5 induction by the pre–T-cell receptor serves as a selective survival signal in T-lymphocyte development
Authors: Berga-Bolaños Rosa , Alberdi Maria , Buxadé Maria , Aramburu José , López-Rodríguez Cristina 
Published: September 2013

SignificanceThe pre–T-cell receptor (pre-TCR) marks a functional checkpoint in thymocyte development that controls functions such as survival, proliferation, and differentiation. Despite knowledge accumulated on signaling pathways activated by the pre-TCR, less is known about the specialization of transcription factors downstream from this receptor and the genes they control. The Relish (Rel)-like transcription factors NF-κB and NFATc were previously known to control specific points of thymocyte maturation. Our work now positions the Rel-like protein NFAT5 as a target of the IKKβ pathway in thymocytes and as a downstream effector of the prosurvival role of the pre-TCR through its ability to regulate the expression of the survival-promoting proteins A1 and Bcl2 and attenuate the proapoptotic axis comprised by p53 and Noxa proteins.
Small-molecule trkB agonists promote axon regeneration in cut peripheral nerves
Authors: English Arthur W. , Liu Kevin , Nicolini Jennifer M. , Mulligan Amanda M. , Ye Keqiang 
Published: September 2013

Significance
If treatments with small-molecule trkB agonists, especially systemically, proved effective in enhancing axon regeneration in injured peripheral nerves, such a result could form the basis for the development of a unique treatment strategy for peripheral nerve injuries.
Hierarchical excitatory synaptic connectivity in mouse olfactory cortex
Authors: McGinley Matthew J. , Westbrook Gary L. 
Published: September 2013

Significance
The dynamics of activity in neural networks form the basis of many brain functions ranging from neural plasticity, memory formation, and sensory perception to consciousness. These dynamics are shaped by immensely complex connectivity patterns of excitatory and inhibitory synapses. Here we used the variance structure of network-wide bursts of excitation to examine connection topology in the olfactory cortex—often viewed as a randomly organized network—and compared it with simulations of several network models. A hierarchical network topology best reproduced the excitatory activity in this cortical region as a result of a subpopulation of neurons (the hierarchy) that generate numerous connections, particularly with members of the same subpopulation. This network organization provides clues to sensory processing in the olfactory cortex.
Human and natural influences on the changing thermal structure of the atmosphere
Authors: Santer Benjamin D. , Painter Jeffrey F. , Bonfils Céline , Mears Carl A. , Solomon Susan , Wigley Tom M. L. , Gleckler Peter J. , Schmidt Gavin A. , Doutriaux Charles , Gillett Nathan P. , Taylor Karl E. , Thorne Peter W. , Wentz Frank J. 
Published: September 2013

SignificanceObservational satellite data and the model-predicted response to human influence have a common latitude/altitude pattern of atmospheric temperature change. The key features of this pattern are global-scale tropospheric warming and stratospheric cooling over the 34-y satellite temperature record. We show that current climate models are highly unlikely to produce this distinctive signal pattern by internal variability alone, or in response to naturally forced changes in solar output and volcanic aerosol loadings. We detect a “human influence” signal in all cases, even if we test against natural variability estimates with much larger fluctuations in solar and volcanic influences than those observed since 1979. These results highlight the very unusual nature of observed changes in atmospheric temperature.
Organellar oligopeptidase (OOP) provides a complementary pathway for targeting peptide degradation in mitochondria and chloroplasts
Authors: Kmiec Beata , Teixeira Pedro F. , Berntsson Ronnie P.-A. , Murcha Monika W. , Branca Rui M. M. , Radomiljac Jordan D. , Regberg Jakob , Svensson Linda M. , Bakali Amin , Langel Ülo , Lehtiö Janne , Whelan James , Stenmark Pål , Glaser Elzbieta 
Published: September 2013

SignificanceImport of proteins to mitochondria and chloroplasts is essential for organelle biogenesis and organism survival. Proteins to be imported contain an N-terminal peptide targeting the protein to the correct organelle. The targeting peptides are cleaved off after the completed import. Because the free targeting peptides are potentially toxic to organellar activities, they must be removed. Here we report the identification and characterization of a unique mitochondrial and chloroplastic oligopeptidase, organellar oligopeptidase, that provides a complementary pathway for the degradation of targeting peptides and also participates in general organellar quality control mechanisms degrading the peptides produced from complete protein degradation.
Reactivation of stalled polyribosomes in synaptic plasticity
Authors: Graber Tyson E. , Hébert-Seropian Sarah , Khoutorsky Arkady , David Alexandre , Yewdell Jonathan W. , Lacaille Jean-Claude , Sossin Wayne S. 
Published: September 2013

SignificanceIn neurons, many mRNAs are transported to synapses in a translationally repressed state, allowing for the spatial and temporal regulation of protein synthesis required for synaptic plasticity. It has been assumed that these mRNAs are repressed at the initiation step of translation. Here we provide evidence for a second mechanism whereby these mRNAs are instead repressed at elongation/termination awaiting translational reactivation upon appropriate synaptic signals. Our results establish that a form of translation-dependent synaptic plasticity, which is dysregulated in neurodevelopmental and psychiatric pathologies, occurs independently of translation initiation. Elucidating the upstream pathways that lead to repression and reactivation of elongation/termination on these mRNAs may provide new avenues for the design of therapies targeting neurodevelopmental disorders.
Whole genome sequencing in patients with retinitis pigmentosa reveals pathogenic DNA structural changes and
NEK2
as a new disease gene
Authors: Nishiguchi Koji M. , Tearle Richard G. , Liu Yangfan P. , Oh Edwin C. , Miyake Noriko , Benaglio Paola , Harper Shyana , Koskiniemi-Kuendig Hanna , Venturini Giulia , Sharon Dror , Koenekoop Robert K. , Nakamura Makoto , Kondo Mineo , Ueno Shinji , Yasuma Tetsuhiro R. , Beckmann Jacques S. , Ikegawa Shiro , Matsumoto Naomichi , Terasaki Hiroko , Berson Eliot L. , Katsanis Nicholas , Rivolta Carlo 
Published: September 2013

Significance
Retinitis pigmentosa (RP) is a genetic disease that causes progressive blindness and that is caused by mutations in more than 50 genes. Conventional methods for identification of both RP mutations and novel RP genes involve the screening of DNA sequences spanning coding exons. In our work, we conversely test the use of whole genome sequencing, a technique that takes into account all variants from both the coding and noncoding regions of the human genome. In our approach, we identify a number of unique RP mutations, a previously undescribed disease gene, as well as pathogenic structural DNA rearrangements originating in introns.
Multiscaled exploration of coupled folding and binding of an intrinsically disordered molecular recognition element in measles virus nucleoprotein
Authors: Wang Yong , Chu Xiakun , Longhi Sonia , Roche Philippe , Han Wei , Wang Erkang , Wang Jin 
Published: September 2013

SignificanceQuantitative understanding of how coupled binding and folding occurs for intrinsically disordered molecular recognition element (MoRE) critical for function is still challenging. By developing an integrated approach, we provided physical quantification of folding and binding energy landscapes of a MoRE at atomistic level. Our predictions are in remarkable agreements with the experiments, and lead to the recognition mechanism via conformational selection, followed by induced folding. We provided an explanation for the underlying connections among “downhill folding,” “molten globule,” and “intrinsic disorder.” We proposed a “kinetic divide-and-conquer” mechanism to understand the high specificity without high affinity in intrinsic disordered protein binding.
Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses
Authors: Essere Boris , Yver Matthieu , Gavazzi Cyrille , Terrier Olivier , Isel Catherine , Fournier Emilie , Giroux Fabienne , Textoris Julien , Julien Thomas , Socratous Clio , Rosa-Calatrava Manuel , Lina Bruno , Marquet Roland , Moules Vincent 
Published: September 2013

Significance
Genetic reassortment is one of the main mechanisms by which pandemic viruses emerge during influenza A coinfection, but little is known about the molecular mechanisms affecting this process. Here, we studied genetic reassortment between a human and an avian influenza A strain, focusing on the generation of reassortant viruses containing the avian HA gene, which have pandemic potential. We found that this genetic process was strongly biased, and we show that packaging signals are crucial for genetic reassortment and that suboptimal compatibility between the segment-specific packaging signals of the two parental viruses limits the emergence of reassortant viruses.
Evidence for a rapid release of carbon at the Paleocene-Eocene thermal maximum
Authors: Wright James D. , Schaller Morgan F. 
Published: September 2013

Significance
Calcium carbonate and carbon isotope records from the rhythmically bedded Marlboro Clay, deposited during the onset of the PETM CIE, show that the massive release of isotopically light carbon was instantaneous, providing important constraints for the magnitude of carbon released and potential mechanisms.
Counting molecules in single organelles with superresolution microscopy allows tracking of the endosome maturation trajectory
Authors: Puchner Elias M. , Walter Jessica M. , Kasper Robert , Huang Bo , Lim Wendell A. 
Published: September 2013

Significance
We combined molecule counting and superresolution microscopy to observe the size, shape, and biomolecular composition of vesicles in the endocytic pathway. From a large number of steady-state snapshots, we follow the maturation of vesicles to endosomes. First, phosphatidylinositol 3-phosphate (PI3P) is generated on newly formed vesicles, principally after they shed their clathrin coat. Next, PI3P sites increase (∼100-fold) on small vesicles whose size is tightly regulated. Finally, the GTPase Vps21 (Rab5 homolog) is associated with small endosomal structures during the initial phase of PI3P production, whereas Ypt7 (Rab7 homolog) localizes to larger endosomal structures, which exhibit saturating levels of PI3P.This new technique opens up the possibility of accurately measuring molecular stoichiometries across several orders of magnitude while resolving subdiffraction-limit organelles.
Network structure and dynamics of the mental workspace
Authors: Schlegel Alexander , Kohler Peter J. , Fogelson Sergey V. , Alexander Prescott , Konuthula Dedeepya , Tse Peter Ulric 
Published: September 2013

SignificanceWe do not know how the human brain mediates complex and creative behaviors such as artistic, scientific, and mathematical thought. Scholars theorize that these abilities require conscious experience as realized in a widespread neural network, or “mental workspace,” that represents and manipulates images, symbols, and other mental constructs across a variety of domains. Evidence for such a complex, interconnected network has been difficult to produce with current techniques that mainly study brain activity in isolation and are insensitive to distributed informational processes. The present work takes advantage of emerging techniques in network and information analysis to provide empirical support for such a widespread and interconnected information processing network in the brain that supports the manipulation of visual imagery.
Structures of human primase reveal design of nucleotide elongation site and mode of Pol α tethering
Authors: Kilkenny Mairi Louise , Longo Michael Anthony , Perera Rajika L. , Pellegrini Luca 
Published: September 2013

Significance
DNA synthesis during duplication of the genome depends on primase, the DNA-dependent RNA polymerase that initiates nucleotide polymerization by assembling short RNA primers on the unwound template DNA. The mechanism of DNA priming remains poorly understood, principally because of lack of high-resolution structural information. Our study begins to fill the gap in our knowledge by reporting crystal structures of human primase in unliganded form and bound to UTP. We exploit the atomic model of primase to map amino acids that are important for the catalytic function of the enzyme. In addition, we describe crystallographically the interaction between primase and DNA polymerase α, which keeps primase tethered to the replication fork.
Blue whale earplug reveals lifetime contaminant exposure and hormone profiles
Authors: Trumble Stephen J. , Robinson Eleanor M. , Berman-Kowalewski Michelle , Potter Charles W. , Usenko Sascha 
Published: September 2013

Significance
Currently, obtaining lifetime chemical profiles (i.e., from birth to death) is extremely rare and difficult for most of Earth’s animals. We have developed a unique approach to quantify hormone and contaminant lifetime profiles for an individual blue whale with a 6-mo resolution using the wax earplug as a natural matrix capable of archiving and preserving these temporal profiles. Using a male blue whale earplug, chemical analysis reveals lifetime patterns of mercury and organic pollutant exposure as well as fluctuating hormone levels. Specifically, we quantified contaminant maternal transfer, time to sexual maturity, and the doubling of stress over the animal’s lifespan. We anticipate that this technique will fundamentally transform our ability to assess human impact on these environmental sentinels and their ecosystems.
Probing the protein-folding mechanism using denaturant and temperature effects on rate constants
Authors: Guinn Emily J. , Kontur Wayne S. , Tsodikov Oleg V. , Shkel Irina , Record M. Thomas 
Published: September 2013

Significance
Analysis of effects of denaturants and temperature on folding and unfolding rate constants of 13 globular proteins yields the amount and composition of the surface buried in folding to and from the high–free-energy transition state (TS), and thereby provides information about folding mechanisms and early unstable folding intermediates. All 13 proteins preferentially bury amide surface in folding to TS; amounts of amide and hydrocarbon surface buried in folding to TS generally exceed those buried in forming the native secondary structure. From this, we conclude that most native secondary structure forms in early unstable folding intermediates and that conversion of these intermediates to TS involves nucleation of tertiary interactions, allowing preferential burial of hydrocarbon surface as TS folds.
GPR171 is a hypothalamic G protein-coupled receptor for BigLEN, a neuropeptide involved in feeding
Authors: Gomes Ivone , Aryal Dipendra K. , Wardman Jonathan H. , Gupta Achla , Gagnidze Khatuna , Rodriguiz Ramona M. , Kumar Sanjai , Wetsel William C. , Pintar John E. , Fricker Lloyd D. , Devi Lakshmi A. 
Published: September 2013

SignificanceThe mechanism by which vertebrate animals control their body weight is a complex process involving a variety of molecules that regulate feeding and metabolism. Some of these molecules are neuropeptides that bind to specific receptors in feeding centers of the brain. One of the most abundant peptides in brain, LENSSPQAPARRLLPP (named BigLEN), has been proposed to function as a neuropeptide involved in regulating body weight, but the receptor through which this peptide acts had not been identified. We screened candidate receptors and found one, G protein-coupled receptor 171 (GPR171), that is activated by BigLEN. Additional studies showed that the BigLEN–GPR171 system plays an important role in regulating feeding and metabolism in mice. Thus, GPR171 is a potential target for developing antiobesity drugs.
A gating mechanism of pentameric ligand-gated ion channels
Authors: Calimet Nicolas , Simoes Manuel , Changeux Jean-Pierre , Karplus Martin , Taly Antoine , Cecchini Marco 
Published: September 2013

SignificancePentameric ligand-gated ion channels (pLGICs) control membrane conductance in living systems from bacteria to humans. Molecular dynamics simulations based on the structures of the prokaryotic channels fromGloeobacter violaceus(GLIC) andErwinia chrysanthemi(ELIC) and the eukaryotic channel fromCaenorhabditis elegans(GluCl) show that the open-to-closed transition begins with a major quaternary (twisting) transition which is followed by tertiary relaxation of the pore-forming helices. The latter is initiated by the outward tilting of the extracellular β-sandwiches in response to agonist unbinding. The proposed atomic resolution mechanism for channel gating, which is in accord with the Monod–Wyman–Changeux model of allostery, is expected to be generally applicable to pLGICs.
C-terminal processing of reaction center protein D1 is essential for the function and assembly of photosystem II inArabidopsis
Authors: Che Yufen , Fu Aigen , Hou Xin , McDonald Kent , Buchanan Bob B. , Huang Weidong , Luan Sheng 
Published: September 2013

SignificanceIn cyanobacteria, the photosystem II (PSII) core subunit, D1, is synthesized as a precursor and must be processed by a C-terminal peptidase before functional PSII can be assembled. Our work shows that in land plants, D1 maturation is not only required for the assembly of a functional PSII, but also is essential for the formation of supercomplexes—structures that are absent in cyanobacteria. This unexpected link opens an avenue for exploring the mechanism for the association of light harvesting complexes with the PSII core complexes—a final step in the development of the naturally occurring form of PSII in land plants.