bluuebunny/crossref_metadata_2025_split huggingface dataset:
Structural determinants of Rab11 activation by the guanine nucleotide exchange factor SH3BP5
Authors: Jenkins Meredith L. , Margaria Jean Piero , Stariha Jordan T. B. , Hoffmann Reece M. , McPhail Jacob A. , Hamelin David J. , Boulanger Martin J. , Hirsch Emilio , Burke John E. 
Published: September 2018

AbstractThe GTPase Rab11 plays key roles in receptor recycling, oogenesis, autophagosome formation, and ciliogenesis. However, investigating Rab11 regulation has been hindered by limited molecular detail describing activation by cognate guanine nucleotide exchange factors (GEFs). Here, we present the structure of Rab11 bound to the GEF SH3BP5, along with detailed characterization of Rab-GEF specificity. The structure of SH3BP5 shows a coiled-coil architecture that mediates exchange through a unique Rab-GEF interaction. Furthermore, it reveals a rearrangement of the switch I region of Rab11 compared with solved Rab-GEF structures, with a constrained conformation when bound to SH3BP5. Mutation of switch I provides insights into the molecular determinants that allow for Rab11 selectivity over evolutionarily similar Rab GTPases present on Rab11-positive organelles. Moreover, we show that GEF-deficient mutants of SH3BP5 show greatly decreased Rab11 activation in cellular assays of active Rab11. Overall, our results give molecular insight into Rab11 regulation, and how Rab-GEF specificity is achieved.
Modular DNA strand-displacement controllers for directing material expansion
Authors: Fern Joshua , Schulman Rebecca 
Published: September 2018

AbstractSoft materials that swell or change shape in response to external stimuli show extensive promise in regenerative medicine, targeted therapeutics, and soft robotics. Generally, a stimulus for shape change must interact directly with the material, limiting the types of stimuli that may be used and necessitating high stimulus concentrations. Here, we show how DNA strand-displacement controllers within hydrogels can mediate size change by interpreting, amplifying, and integrating stimuli and releasing signals that direct the response. These controllers tune the time scale and degree of DNA-crosslinked hydrogel swelling and can actuate dramatic material size change in response to <100 nM of a specific biomolecular input. Controllers can also direct swelling in response to small molecules or perform logic. The integration of these stimuli-responsive materials with biomolecular circuits is a major step towards autonomous soft robotic systems in which sensing and actuation are implemented by biomolecular reaction networks.
New suspension-feeding radiodont suggests evolution of microplanktivory in Cambrian macronekton
Authors: Lerosey-Aubril Rudy , Pates Stephen 
Published: September 2018

AbstractThe rapid diversification of metazoans and their organisation in modern-style marine ecosystems during the Cambrian profoundly transformed the biosphere. What initially sparked this Cambrian explosion remains passionately debated, but the establishment of a coupling between pelagic and benthic realms, a key characteristic of modern-day oceans, might represent a primary ecological cause. By allowing the transfer of biomass and energy from the euphotic zone—the locus of primary production—to the sea floor, this biological pump would have boosted diversification within the emerging metazoan-dominated benthic communities. However, little is known about Cambrian pelagic organisms and their trophic interactions. Here we describe a filter-feeding Cambrian radiodont exhibiting morphological characters that likely enabled the capture of microplankton-sized particles, including large phytoplankton. This description of a large free-swimming suspension-feeder potentially engaged in primary consumption suggests a more direct involvement of nekton in the establishment of an oceanic pelagic-benthic coupling in the Cambrian.
Selective reduction and homologation of carbon monoxide by organometallic iron complexes
Authors: Sharpe Helen R. , Geer Ana M. , Taylor Laurence J. , Gridley Benjamin M. , Blundell Toby J. , Blake Alexander J. , Davies E. Stephen , Lewis William , McMaster Jonathan , Robinson David , Kays Deborah L. 
Published: September 2018

AbstractCarbon monoxide is a key C1 feedstock for the industrial production of hydrocarbons, where it is used to make millions of tonnes of chemicals, fuels, and solvents per annum. Many transition metal complexes can coordinate CO, but the formation of new C−C bonds in well-defined compounds from the scission and subsequent coupling of two or more CO moieties at a transition metal centre remains a challenge. Herein, we report the use of low-coordinate iron(II) complexes for the selective scission and homologation of CO affording unusual squaraines and iron carboxylates at ambient temperature and pressure. A modification of the ligand framework allows for the isolation and structural characterisation of a proposed metallacyclic Fe(II) carbene intermediate. These results indicate that, with the appropriate choice of supporting ligands, it is possible to cleave and homologate carbon monoxide under mild conditions using an abundant and environmentally benign low-coordinate, first row transition metal.
Mapping a hidden terrane boundary in the mantle lithosphere with lamprophyres
Authors: Dijkstra Arjan H. , Hatch Callum 
Published: September 2018

AbstractLamprophyres represent hydrous alkaline mantle melts that are a unique source of information about the composition of continental lithosphere. Throughout southwest Britain, post-Variscan lamprophyres are (ultra)potassic with strong incompatible element enrichments. Here we show that they form two distinct groups in terms of their Sr and Nd isotopic compositions, occurring on either side of a postulated, hitherto unrecognized terrane boundary. Lamprophyres emplaced north of the boundary fall on the mantle array with εNd −1 to +1.6. Those south of the boundary are enriched in radiogenic Sr, have initial εNd values of −0.3 to −3.5, and are isotopically indistinguishable from similar-aged lamprophyres in Armorican massifs in Europe. We conclude that an Armorican terrane was juxtaposed against Avalonia well before the closure of the Variscan oceans and the formation of Pangea. The giant Cornubian Tin-Tungsten Ore Province and associated batholith can be accounted for by the fertility of Armorican lower crust and mantle lithosphere.
CD69 prevents PLZFhi innate precursors from prematurely exiting the thymus and aborting NKT2 cell differentiation
Authors: Kimura Motoko Y. , Igi Akemi , Hayashizaki Koji , Mita Yukiyoshi , Shinzawa Miho , Kadakia Tejas , Endo Yukihiro , Ogawa Satomi , Yagi Ryoji , Motohashi Shinichiro , Singer Alfred , Nakayama Toshinori 
Published: September 2018

AbstractWhile CD69 may regulate thymocyte egress by inhibiting S1P1expression, CD69 expression is not thought to be required for normal thymocyte development. Here we show that CD69 is in fact specifically required for the differentiation of mature NKT2 cells, which do not themselves express CD69. Mechanistically, CD69 expression is required on CD24+PLZFhiinnate precursors for their retention in the thymus and completion of their differentiation into mature NKT2 cells. By contrast, CD69-deficient CD24+PLZFhiinnate precursors express S1P1and prematurely exit the thymus, while S1P1inhibitor treatment of CD69-deficient mice retains CD24+PLZFhiinnate precursors in the thymus and restores NKT2 cell differentiation. Thus, CD69 prevents S1P1expression on CD24+PLZFhiinnate precursor cells from aborting NKT2 differentiation in the thymus. This study reveals the importance of CD69 to prolong the thymic residency time of developing immature precursors for proper differentiation of a T cell subset.
Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex
Authors: Zhou Haocheng , Zhang Qiaosheng , Martinez Erik , Dale Jahrane , Hu Sile , Zhang Eric , Liu Kevin , Huang Dong , Yang Guang , Chen Zhe , Wang Jing 
Published: September 2018

AbstractChronic pain is known to induce an amplified aversive reaction to peripheral nociceptive inputs. This enhanced affective response constitutes a key pathologic feature of chronic pain syndromes such as fibromyalgia. However, the neural mechanisms that underlie this important aspect of pain processing remain poorly understood, hindering the development of treatments. Here, we show that a single dose of ketamine can produce a persistent reduction in the aversive response to noxious stimuli in rodent chronic pain models, long after the termination of its anti-nociceptive effects. Furthermore, we demonstrated that this anti-aversive property is mediated by prolonged suppression of the hyperactivity of neurons in the anterior cingulate cortex (ACC), a brain region well known to regulate pain affect. Therefore, our results indicate that it is feasible to dissociate the affective from the sensory component of pain, and demonstrate the potential for low-dose ketamine to be an important therapy for chronic pain syndromes.
UPF1-like helicase grip on nucleic acids dictates processivity
Authors: Kanaan Joanne , Raj Saurabh , Decourty Laurence , Saveanu Cosmin , Croquette Vincent , Le Hir Hervé 
Published: September 2018

AbstractHelicases are molecular engines which translocate along nucleic acids (NA) to unwind double-strands or remodel NA–protein complexes. While they have an essential role in genome structure and expression, the rules dictating their processivity remain elusive. Here, we developed single-molecule methods to investigate helicase binding lifetime on DNA. We found that UPF1, a highly processive helicase central to nonsense-mediated mRNA decay (NMD), tightly holds onto NA, allowing long lasting action. Conversely, the structurally similar IGHMBP2 helicase has a short residence time. UPF1 mutants with variable grip on DNA show that grip tightness dictates helicase residence time and processivity. In addition, we discovered via functional studies that a decrease in UPF1 grip impairs NMD efficiency in vivo. Finally, we propose a three-state model with bound, sliding and unbound molecular clips, that can accurately predict the modulation of helicase processivity.
Predicting proteome dynamics using gene expression data
Authors: Kuchta Krzysztof , Towpik Joanna , Biernacka Anna , Kutner Jan , Kudlicki Andrzej , Ginalski Krzysztof , Rowicka Maga 
Published: September 2018

AbstractWhile protein concentrations are physiologically most relevant, measuring them globally is challenging. mRNA levels are easier to measure genome-wide and hence are typically used to infer the corresponding protein abundances. The steady-state condition (assumption that protein levels remain constant) has typically been used to calculate protein concentrations, as it is mathematically convenient, even though it is often not satisfied. Here, we propose a method to estimate genome-wide protein abundances without this assumption. Instead, we assume that the system returns to its baseline at the end of the experiment, which is true for cyclic phenomena (e.g. cell cycle) and many time-course experiments. Our approach only requires availability of gene expression and protein half-life data. As proof-of-concept, we predicted proteome dynamics associated with the budding yeast cell cycle, the results are available for browsing online at http://dynprot.cent.uw.edu.pl/. The approach was validated experimentally by verifying that the predicted protein concentration changes were consistent with measurements for all proteins tested. Additionally, if proteomic data are available as well, we can also infer changes in protein half-lives in response to posttranslational regulation, as we did for Clb2, a post-translationally regulated protein. The predicted changes in Clb2 abundance are consistent with earlier observations.
Epidemiological tracing of Batrachochytrium salamandrivorans identifies widespread infection and associated mortalities in private amphibian collections
Authors: Fitzpatrick Liam D. , Pasmans Frank , Martel An , Cunningham Andrew A. 
Published: September 2018

AbstractThe amphibian chytrid fungus Batrachochytrium salamandrivorans (Bsal) infects newts and salamanders (urodele amphibians), in which it can cause fatal disease. This pathogen has caused dramatic fire salamander population declines in Belgium, the Netherlands and Germany since its discovery in 2010. Thought to be native to Asia, it has been hypothesised that Bsal was introduced to Europe with the importation of infected amphibians for the commercial pet trade. Following the discovery of Bsal in captive amphibians in the United Kingdom in 2015, we used contact-tracing to identify epidemiologically-linked private amphibian collections in Western Europe. Of 16 linked collections identified, animals were tested from 11 and urodeles tested positive for Bsal in seven, including the identification of the pathogen in Spain for the first time. Mortality of Bsal-positive individuals was observed in five collections. Our results indicate that Bsal is likely widespread within the private amphibian trade, at least in Europe. These findings are important for informing policy regarding Bsal control strategies.
Deep Brain Stimulation for Parkinson’s disease changes perception in the Rubber Hand Illusion
Authors: Ding Catherine , Palmer Colin J. , Hohwy Jakob , Youssef George J. , Paton Bryan , Tsuchiya Naotsugu , Stout Julie C. , Thyagarajan Dominic 
Published: September 2018

AbstractParkinson’s disease (PD) alters cortico-basal ganglia-thalamic circuitry and susceptibility to an illusion of bodily awareness, the Rubber Hand Illusion (RHI). Bodily awareness is thought to result from multisensory integration in a predominantly cortical network; the role of subcortical connections is unknown. We studied the effect of modulating cortico-subcortical circuitry on multisensory integration for bodily awareness in 24 PD patients treated with subthalamic nucleus (STN) deep brain stimulation (DBS), in comparison to 21 healthy volunteers, using the RHI experiment. Typically, synchronous visuo-tactile cues induce a false perception of touch on the rubber hand as if it were the subject’s hand, whereas asynchronous visuo-tactile cues do not. However, we found that in the asynchronous condition, patients in the off-stimulation state did not reject the RHI as strongly as healthy controls; patients’ rejection of the RHI strengthened when STN-DBS was switched on, although it remained weaker than that of controls. Patients in the off-stimulation state also misjudged the position of their hand, indicating it to be closer to the rubber hand than controls. However, STN-DBS did not affect proprioceptive judgements or subsequent arm movements altered by the perceptual effects of the illusion. Our findings support the idea that the STN and subcortical connections have a key role in multisensory integration for bodily awareness. Decision-making in multisensory bodily illusions is discussed.
Proline provides site-specific flexibility for in vivo collagen
Authors: Chow Wing Ying , Forman Chris J. , Bihan Dominique , Puszkarska Anna M. , Rajan Rakesh , Reid David G. , Slatter David A. , Colwell Lucy J. , Wales David J. , Farndale Richard W. , Duer Melinda J. 
Published: September 2018

AbstractFibrillar collagens have mechanical and biological roles, providing tissues with both tensile strength and cell binding sites which allow molecular interactions with cell-surface receptors such as integrins. A key question is: how do collagens allow tissue flexibility whilst maintaining well-defined ligand binding sites? Here we show that proline residues in collagen glycine-proline-hydroxyproline (Gly-Pro-Hyp) triplets provide local conformational flexibility, which in turn confers well-defined, low energy molecular compression-extension and bending, by employing two-dimensional 13C-13C correlation NMR spectroscopy on 13C-labelled intact ex vivo bone and in vitro osteoblast extracellular matrix. We also find that the positions of Gly-Pro-Hyp triplets are highly conserved between animal species, and are spatially clustered in the currently-accepted model of molecular ordering in collagen type I fibrils. We propose that the Gly-Pro-Hyp triplets in fibrillar collagens provide fibril “expansion joints” to maintain molecular ordering within the fibril, thereby preserving the structural integrity of ligand binding sites.
In vitro protein expression changes in RAW 264.7 cells and HUVECs treated with dialyzed coffee extract by immunoprecipitation high performance liquid chromatography
Authors: Yoon Cheol Soo , Kim Min Keun , Kim Yeon Sook , Lee Suk Keun 
Published: September 2018

AbstractRAW 264.7 cells and HUVECs were compared to evaluate the effects of dialyzed coffee extract (DCE) and artificial coffee (AC). Immunoprecipitation high performance liquid chromatography (IP-HPLC) showed DCE-2.5- (equivalent to 2.5 cups of coffee a day) and DCE-5-induced protein expression that was beneficial to human health, i.e., they led to significant increases in proliferation-, immunity-, cellular protection-, antioxidant signaling-, and osteogenesis-related proteins but decreases in inflammation-, NFkB signaling-, cellular apoptosis-, and oncogenic signaling-related proteins in RAW 264.7 cells, and slight decreases in angiogenesis-related proteins in HUVECs. These protein expression changes were less frequently observed for DCE-10 treatment, while AC treatment induced very different changes in protein expression. We suggest that the favorable cellular effects of DCE were derived from minor coffee elements that were absent in AC, and that the reduced effects of DCE-10 compared with those of DCE-2.5 or DCE-5 might have been caused by greater adverse reactions to caffeine and chlorogenic acid in DCE-10 than DCE-2.5 or DCE-5. IP-HPLC results suggested that minor coffee elements in DCE might play beneficial roles in the global protein expression of proliferation-, immunity-, anti-inflammation-, cell protection-, antioxidant-, anti-apoptosis-, anti-oncogenesis-, and osteogenesis-related proteins in RAW 264.7 cells and enhance anti-angiogenic signaling in HUVECs.
A facile synthesis of Au-nanoparticles decorated PbI2 single crystalline nanosheets for optoelectronic device applications
Authors: Shkir Mohd. , Yahia I. S. , Ganesh V. , Bitla Y. , Ashraf I. M. , Kaushik Ajeet , AlFaify S. 
Published: September 2018

AbstractThis research communication presents a rapid and facile microwave-assisted synthesis of single crystalline nanosheets (SCNSs) of hexagonal lead iodide (PbI2) decorated with Au nanoparticles, a potential optoelectronics material. Homogeneous low dimensional AuNP decoration in PbI2 resulted in a new absorption band at ~604 nm and a shift in band gap from 3.23 to 3.00 eV. The significant enhancement of photoluminescent (PL) intensity observed in the AuNP-PbI2 SCNSs is attributed to the coupling of the localized surface plasmon resonanzce of AuNP leading to improved excitation and emission rates of PbI2-SCNSs in the region of the localized electromagnetic field. The Au-PbI2 SCNSs display a compelling increment in photoconductivity, and its fabricated photodetector showed a stable and switchable photo-response. Due to ease of synthesis and enhanced photoconductivity along with appealing PL features, Au-PbI2 SCNS has the potential to be used as a material of choice when fabricating an optoelectronic devices of high performance.
Evidence for the beneficial effect of perceptual grouping on visual working memory: an empirical study on illusory contour and a meta-analytic study
Authors: Li Jiaofeng , Qian Jiehui , Liang Fan 
Published: September 2018

AbstractThe capacity of visual working memory (VWM) is found to be extremely limited. Past research shows that VWM can be facilitated by Gestalt principles of grouping, however, it remains controversial whether factors like the type of Gestalt principles, the characteristics of stimuli and the nature of experimental design could affect the beneficial effect of grouping. In particular, studies have shown that perceptual grouping could improve memory performance for a feature that is relevant for grouping, but it is unclear whether the same improvement exists for a feature that is irrelevant for grouping. In this article, an empirical study and a meta-analytic study were conducted to investigate the effect of perceptual grouping on VWM. In the empirical study, we examined the grouping effect by employing a Kanizsa illusion in which memory items were grouped by illusory contour. We found that the memory performance was improved for the grouped items even though the tested feature was grouping irrelevant, and the improvement was not significantly different from the effect of grouping by physical connectedness or by solid occlusion. In the meta-analytic study, we systematically and quantitatively examined the effect of perceptual grouping on VWM by pulling the results from all eligible studies, and found that the beneficial grouping effect was robust but the magnitude of the effect can be affected by several moderators. Factors like the types of grouping methods, the duration and the layout of the memory display, and the characteristics of the tested feature moderated the grouping effect, whereas whether employing a cue or a verbal suppression task did not. Our study suggests that the underlying mechanism of the grouping benefit may be distinct with regard to grouping relevancy of the to-be-stored feature. The grouping effect on VWM may be independent of attention for a grouping relevant feature, but may rely on attentional prioritization for a grouping irrelevant feature.
Summertime Primary and Secondary Contributions to Southern Ocean Cloud Condensation Nuclei
Authors: Fossum Kirsten N. , Ovadnevaite Jurgita , Ceburnis Darius , Dall’Osto Manuel , Marullo Salvatore , Bellacicco Marco , Simó Rafel , Liu Dantong , Flynn Michael , Zuend Andreas , O’Dowd Colin 
Published: September 2018

AbstractAtmospheric aerosols in clean remote oceanic regions contribute significantly to the global albedo through the formation of haze and cloud layers; however, the relative importance of ‘primary’ wind-produced sea-spray over secondary (gas-to-particle conversion) sulphate in forming marine clouds remains unclear. Here we report on marine aerosols (PM1) over the Southern Ocean around Antarctica, in terms of their physical, chemical, and cloud droplet activation properties. Two predominant pristine air masses and aerosol populations were encountered: modified continental Antarctic (cAA) comprising predominantly sulphate with minimal sea-salt contribution and maritime Polar (mP) comprising sulphate plus sea-salt. We estimate that in cAA air, 75% of the CCN are activated into cloud droplets while in mP air, 37% are activated into droplets, for corresponding peak supersaturation ranges of 0.37–0.45% and 0.19–0.31%, respectively. When realistic marine boundary layer cloud supersaturations are considered (e.g. ~0.2–0.3%), sea-salt CCN contributed 2–13% of the activated nuclei in the cAA air and 8–51% for the marine air for surface-level wind speed < 16 m s−1. At higher wind speeds, primary marine aerosol can even contribute up to 100% of the activated CCN, for corresponding peak supersaturations as high as 0.32%.