bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dynamic disorganization of synaptic NMDA receptors triggered by autoantibodies from psychotic patients
Authors: Jézéquel Julie , Johansson Emily M. , Dupuis Julien P. , Rogemond Véronique , Gréa Hélène , Kellermayer Blanka , Hamdani Nora , Le Guen Emmanuel , Rabu Corentin , Lepleux Marilyn , Spatola Marianna , Mathias Elodie , Bouchet Delphine , Ramsey Amy J. , Yolken Robert H. , Tamouza Ryad , Dalmau Josep , Honnorat Jérôme , Leboyer Marion , Groc Laurent 
Published: November 2017

AbstractThe identification of circulating autoantibodies against neuronal receptors in neuropsychiatric disorders has fostered new conceptual and clinical frameworks. However, detection reliability, putative presence in different diseases and in health have raised questions about potential pathogenic mechanism mediated by autoantibodies. Using a combination of single molecule-based imaging approaches, we here ascertain the presence of circulating autoantibodies against glutamate NMDA receptor (NMDAR-Ab) in about 20% of psychotic patients diagnosed with schizophrenia and very few healthy subjects. NMDAR-Ab from patients and healthy subjects do not compete for binding on native receptor. Strikingly, NMDAR-Ab from patients, but not from healthy subjects, specifically alter the surface dynamics and nanoscale organization of synaptic NMDAR and its anchoring partner the EphrinB2 receptor in heterologous cells, cultured neurons and in mouse brain. Functionally, only patients’ NMDAR-Ab prevent long-term potentiation at glutamatergic synapses, while leaving NMDAR-mediated calcium influx intact. We unveil that NMDAR-Ab from psychotic patients alter NMDAR synaptic transmission, supporting a pathogenically relevant role.
Reconstitution of the complete pathway of ITS2 processing at the pre-ribosome
Authors: Fromm Lisa , Falk Sebastian , Flemming Dirk , Schuller Jan Michael , Thoms Matthias , Conti Elena , Hurt Ed 
Published: November 2017

AbstractRemoval of internal transcribed spacer 2 (ITS2) from pre-ribosomal RNA is essential to make functional ribosomes. This complicated processing reaction begins with a single endonucleolytic cleavage followed by exonucleolytic trimming at both new cleavage sites to generate mature 5.8S and 25S rRNA. We reconstituted the 7S→5.8S processing branch within ITS2 using purified exosome and its nuclear cofactors. We find that both Rrp44’s ribonuclease activities are required for initial RNA shortening followed by hand over to the exonuclease Rrp6. During the in vitro reaction, ITS2-associated factors dissociate and the underlying ‘foot’ structure of the pre-60S particle is dismantled. 7S pre-rRNA processing is independent of 5S RNP rotation, but 26S→25S trimming is a precondition for subsequent 7S→5.8S processing. To complete the in vitro assay, we reconstituted the entire cycle of ITS2 removal with a total of 18 purified factors, catalysed by the integrated activities of the two participating RNA-processing machines, the Las1 complex and nuclear exosome.
Rods progressively escape saturation to drive visual responses in daylight conditions
Authors: Tikidji-Hamburyan Alexandra , Reinhard Katja , Storchi Riccardo , Dietter Johannes , Seitter Hartwig , Davis Katherine E. , Idrees Saad , Mutter Marion , Walmsley Lauren , Bedford Robert A. , Ueffing Marius , Ala-Laurila Petri , Brown Timothy M. , Lucas Robert J. , Münch Thomas A. 
Published: November 2017

AbstractRod and cone photoreceptors support vision across large light intensity ranges. Rods, active under dim illumination, are thought to saturate at higher (photopic) irradiances. The extent of rod saturation is not well defined; some studies report rod activity well into the photopic range. Using electrophysiological recordings from retina and dorsal lateral geniculate nucleus of cone-deficient and visually intact mice, we describe stimulus and physiological factors that influence photopic rod-driven responses. We find that rod contrast sensitivity is initially strongly reduced at high irradiances, but progressively recovers to allow responses to moderate contrast stimuli. Surprisingly, rods recover faster at higher light levels. A model of rod phototransduction suggests that phototransduction gain adjustments and bleaching adaptation underlie rod recovery. Consistently, exogenous chromophore reduces rod responses at bright background. Thus, bleaching adaptation renders mouse rods responsive to modest contrast at any irradiance. Paradoxically, raising irradiance across the photopic range increases the robustness of rod responses.
The STUbL RNF4 regulates protein group SUMOylation by targeting the SUMO conjugation machinery
Authors: Kumar Ramesh , González-Prieto Román , Xiao Zhenyu , Verlaan-de Vries Matty , Vertegaal Alfred C. O. 
Published: November 2017

AbstractSUMO-targeted ubiquitin ligases (STUbLs) mediate the ubiquitylation of SUMOylated proteins to modulate their functions. In search of direct targets for the STUbL RNF4, we have developed TULIP (targets for ubiquitin ligases identified by proteomics) to covalently trap targets for ubiquitin E3 ligases. TULIP methodology could be widely employed to delineate E3 substrate wiring. Here we report that the single SUMO E2 Ubc9 and the SUMO E3 ligases PIAS1, PIAS2, PIAS3, ZNF451, and NSMCE2 are direct RNF4 targets. We confirm PIAS1 as a key RNF4 substrate. Furthermore, we establish the ubiquitin E3 ligase BARD1, a tumor suppressor and partner of BRCA1, as an indirect RNF4 target, regulated by PIAS1. Interestingly, accumulation of BARD1 at local sites of DNA damage increases upon knockdown of RNF4. Combined, we provide an insight into the role of the STUbL RNF4 to balance the role of SUMO signaling by directly targeting Ubc9 and SUMO E3 ligases.
Gate-tunable large magnetoresistance in an all-semiconductor spin valve device
Authors: Oltscher M. , Eberle F. , Kuczmik T. , Bayer A. , Schuh D. , Bougeard D. , Ciorga M. , Weiss D. 
Published: November 2017

AbstractA large spin-dependent and electric field-tunable magnetoresistance of a two-dimensional electron system is a key ingredient for the realization of many novel concepts for spin-based electronic devices. The low magnetoresistance observed during the last few decades in devices with lateral semiconducting transport channels between ferromagnetic source and drain contacts has been the main obstacle for realizing spin field effect transistor proposals. Here, we show both a large two-terminal magnetoresistance in a lateral spin valve device with a two-dimensional channel, with up to 80% resistance change, and tunability of the magnetoresistance by an electric gate. The enhanced magnetoresistance is due to finite electric field effects at the contact interface, which boost spin-to-charge conversion. The gating scheme that we use is based on switching between uni- and bidirectional spin diffusion, without resorting to spin–orbit coupling. Therefore, it can also be employed in materials with low spin–orbit coupling.
A bioreducible N-oxide-based probe for photoacoustic imaging of hypoxia
Authors: Knox Hailey J. , Hedhli Jamila , Kim Tae Wook , Khalili Kian , Dobrucki Lawrence W. , Chan Jefferson 
Published: November 2017

AbstractHypoxia occurs when limited oxygen supply impairs physiological functions and is a pathological hallmark of many diseases including cancer and ischemia. Thus, detection of hypoxia can guide treatment planning and serve as a predictor of patient prognosis. Unfortunately, current methods suffer from invasiveness, poor resolution and low specificity. To address these limitations, we present Hypoxia Probe 1 (HyP-1), a hypoxia-responsive agent for photoacoustic imaging. This emerging modality converts safe, non-ionizing light to ultrasound waves, enabling acquisition of high-resolution 3D images in deep tissue. HyP-1 features an N-oxide trigger that is reduced in the absence of oxygen by heme proteins such as CYP450 enzymes. Reduction of HyP-1 produces a spectrally distinct product, facilitating identification via photoacoustic imaging. HyP-1 exhibits selectivity for hypoxic activation in vitro, in living cells, and in multiple disease models in vivo. HyP-1 is also compatible with NIR fluorescence imaging, establishing its versatility as a multimodal imaging agent.
Meta-analysis of gut microbiome studies identifies disease-specific and shared responses
Authors: Duvallet Claire , Gibbons Sean M. , Gurry Thomas , Irizarry Rafael A. , Alm Eric J. 
Published: November 2017

AbstractHundreds of clinical studies have demonstrated associations between the human microbiome and disease, yet fundamental questions remain on how we can generalize this knowledge. Results from individual studies can be inconsistent, and comparing published data is further complicated by a lack of standard processing and analysis methods. Here we introduce the MicrobiomeHD database, which includes 28 published case–control gut microbiome studies spanning ten diseases. We perform a cross-disease meta-analysis of these studies using standardized methods. We find consistent patterns characterizing disease-associated microbiome changes. Some diseases are associated with over 50 genera, while most show only 10–15 genus-level changes. Some diseases are marked by the presence of potentially pathogenic microbes, whereas others are characterized by a depletion of health-associated bacteria. Furthermore, we show that about half of genera associated with individual studies are bacteria that respond to more than one disease. Thus, many associations found in case–control studies are likely not disease-specific but rather part of a non-specific, shared response to health and disease.
Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2
Authors: Elango Rajula , Sheng Ziwei , Jackson Jessica , DeCata Jenna , Ibrahim Younis , Pham Nhung T. , Liang Diana H. , Sakofsky Cynthia J. , Vindigni Alessandro , Lobachev Kirill S. , Ira Grzegorz , Malkova Anna 
Published: November 2017

AbstractBreak-induced replication (BIR) is a DNA double-strand break repair pathway that leads to genomic instabilities similar to those observed in cancer. BIR proceeds by a migrating bubble where asynchrony between leading and lagging strand synthesis leads to accumulation of long single-stranded DNA (ssDNA). It remains unknown how this ssDNA is prevented from unscheduled pairing with the template, which can lead to genomic instability. Here, we propose that uncontrolled Rad51 binding to this ssDNA promotes formation of toxic joint molecules that are counteracted by Srs2. First, Srs2 dislodges Rad51 from ssDNA preventing promiscuous strand invasions. Second, it dismantles toxic intermediates that have already formed. Rare survivors in the absence of Srs2 rely on structure-specific endonucleases, Mus81 and Yen1, that resolve toxic joint-molecules. Overall, we uncover a new feature of BIR and propose that tight control of ssDNA accumulated during this process is essential to prevent its channeling into toxic structures threatening cell viability.
Longer aftershocks duration in extensional tectonic settings
Authors: Valerio E. , Tizzani P. , Carminati E. , Doglioni C. 
Published: November 2017

AbstractAftershocks number decay through time, depending on several parameters peculiar to each seismogenic regions, including mainshock magnitude, crustal rheology, and stress changes along the fault. However, the exact role of these parameters in controlling the duration of the aftershock sequence is still unknown. Here, using two methodologies, we show that the tectonic setting primarily controls the duration of aftershocks. On average and for a given mainshock magnitude (1) aftershock sequences are longer and (2) the number of earthquakes is greater in extensional tectonic settings than in contractional ones. We interpret this difference as related to the different type of energy dissipated during earthquakes. In detail, (1) a joint effect of gravitational forces and pure elastic stress release governs extensional earthquakes, whereas (2) pure elastic stress release controls contractional earthquakes. Accordingly, normal faults operate in favour of gravity, preserving inertia for a longer period and seismicity lasts until gravitational equilibrium is reached. Vice versa, thrusts act against gravity, exhaust their inertia faster and the elastic energy dissipation is buffered by the gravitational force. Hence, for seismic sequences of comparable magnitude and rheological parameters, aftershocks last longer in extensional settings because gravity favours the collapse of the hangingwall volumes.
Genotyping-by-Sequencing Derived High-Density Linkage Map and its Application to QTL Mapping of Flag Leaf Traits in Bread Wheat
Authors: Hussain Waseem , Baenziger P. Stephen. , Belamkar Vikas , Guttieri Mary J. , Venegas Jorge P. , Easterly Amanda , Sallam Ahmed , Poland Jesse 
Published: November 2017

AbstractWinter wheat parents ‘Harry’ (drought tolerant) and ‘Wesley’ (drought susceptible) were used to develop a recombinant inbred population with future goals of identifying genomic regions associated with drought tolerance. To precisely map genomic regions, high-density linkage maps are a prerequisite. In this study genotyping-by- sequencing (GBS) was used to construct the high-density linkage map. The map contained 3,641 markers distributed on 21 chromosomes and spanned 1,959 cM with an average distance of 1.8 cM between markers. The constructed linkage map revealed strong collinearity in marker order across 21 chromosomes with POPSEQ-v2.0, which was based on a high-density linkage map. The reliability of the linkage map for QTL mapping was demonstrated by co-localizing the genes to previously mapped genomic regions for two highly heritable traits, chaff color, and leaf cuticular wax. Applicability of linkage map for QTL mapping of three quantitative traits, flag leaf length, width, and area, identified 21 QTLs in four environments, and QTL expression varied across the environments. Two major stable QTLs, one each for flag leaf length (Qfll.hww-7A) and flag leaf width (Qflw.hww-5A) were identified. The map constructed will facilitate QTL and fine mapping of quantitative traits, map-based cloning, comparative mapping, and in marker-assisted wheat breeding endeavors.
Prediction of postoperative outcomes using intraoperative hemodynamic monitoring data
Authors: Prasad Varesh , Guerrisi Maria , Dauri Mario , Coniglione Filadelfo , Tisone Giuseppe , De Carolis Elisa , Cillis Annagrazia , Canichella Antonio , Toschi Nicola , Heldt Thomas 
Published: November 2017

AbstractMajor surgeries can result in high rates of adverse postoperative events. Reliable prediction of which patient might be at risk for such events may help guide peri- and postoperative care. We show how archiving and mining of intraoperative hemodynamic data in orthotopic liver transplantation (OLT) can aid in the prediction of postoperative 180-day mortality and acute renal failure (ARF), improving upon predictions that rely on preoperative information only. From 101 patient records, we extracted 15 preoperative features from clinical records and 41 features from intraoperative hemodynamic signals. We used logistic regression with leave-one-out cross-validation to predict outcomes, and incorporated methods to limit potential model instabilities from feature multicollinearity. Using only preoperative features, mortality prediction achieved an area under the receiver operating characteristic curve (AUC) of 0.53 (95% CI: 0.44–0.78). By using intraoperative features, performance improved significantly to 0.82 (95% CI: 0.56–0.91, P = 0.001). Similarly, including intraoperative features (AUC = 0.82; 95% CI: 0.66–0.94) in ARF prediction improved performance over preoperative features (AUC = 0.72; 95% CI: 0.50–0.85), though not significantly (P = 0.32). We conclude that inclusion of intraoperative hemodynamic features significantly improves prediction of postoperative events in OLT. Features strongly associated with occurrence of both outcomes included greater intraoperative central venous pressure and greater transfusion volumes.
Nav channel binder containing a specific conjugation-site based on a low toxicity β-scorpion toxin
Authors: Kubota Tomoya , Dang Bobo , Carvalho-de-Souza Joao L. , Correa Ana M. , Bezanilla Francisco 
Published: November 2017

AbstractVoltage-gated sodium (Nav) channels play a key role in generating action potentials which leads to physiological signaling in excitable cells. The availability of probes for functional studies of mammalian Nav is limited. Here, by introducing two amino acid substitutions into the beta scorpion toxin Ts1, we have chemically synthesized a novel binder [S14R, W50Pra]Ts1 for Nav with high affinity, low dissociation rate and reduced toxicity while retaining the capability of conjugating Ts1 with molecules of interests for different applications. Using the fluorescent-dye conjugate, [S14R, W50Pra(Bodipy)]Ts1, we confirmed its binding to Nav1.4 through Lanthanide-based Resonance Energy Transfer. Moreover, using the gold nanoparticle conjugate, [S14R, W50Pra(AuNP)]Ts1, we were able to optically stimulate dorsal root ganglia neurons and generate action potentials with visible light via the optocapacitive effect as previously reported. [S14R, W50Pra]Ts1 is a novel probe with great potential for wider applications in Nav-related neuroscience research.
Anions for Near-Infrared Selective Organic Salt Photovoltaics
Authors: Traverse Christopher J. , Young Margaret , Suddard-Bangsund John , Patrick Tyler , Bates Matthew , Chen Pei , Wingate Brian , Lunt Sophia Y. , Anctil Annick , Lunt Richard R. 
Published: November 2017

AbstractOrganic molecular salts are an emerging and highly tunable class of materials for organic and transparent photovoltaics. In this work, we demonstrate novel phenyl borate and carborane-based anions paired with a near-infrared (NIR)-selective heptamethine cation. We further explore the effects of anion structures and functional groups on both device performance and physical properties. Changing the functional groups on the anion significantly alters the open circuit voltage and yields a clear dependence on electron withdrawing groups. Anion exchange is also shown to selectively alter the solubility and film surface energy of the resulting molecular salt, enabling the potential fabrication of solution-deposited cascade or multi-junction devices from orthogonal solvents. This study further expands the catalog and properties of organic salts for inexpensive, and stable NIR-selective molecular salt photovoltaics.
Frequency and reactivity of antigen-specific T cells were concurrently measured through the combination of artificial antigen-presenting cell, MACS and ELISPOT
Authors: Shen Chuanlai , Xu Tao , Wu You , Li Xiaoe , Xia Lingzhi , Wang Wei , Shahzad Khawar Ali , Zhang Lei , Wan Xin , Qiu Jie 
Published: November 2017

AbstractConventional peptide-major histocompatibility complex (pMHC) multimer staining, intracellular cytokine staining, and enzyme-linked immunospot (ELISPOT) assay cannot concurrently determine the frequency and reactivity of antigen-specific T cells (AST) in a single assay. In this report, pMHC multimer, magnetic-activated cell sorting (MACS), and ELISPOT techniques have been integrated into a micro well by coupling pMHC multimers onto cell-sized magnetic beads to characterize AST cell populations in a 96-well microplate which pre-coated with cytokine-capture antibodies. This method, termed AAPC-microplate, allows the enumeration and local cytokine production of AST cells in a single assay without using flow cytometry or fluorescence intensity scanning, thus will be widely applicable. Here, ovalbumin257–264-specific CD8+T cells from OT-1 T cell receptor (TCR) transgenic mice were measured. The methodological accuracy, specificity, reproducibility, and sensitivity in enumerating AST cells compared well with conventional pMHC multimer staining. Furthermore, the AAPC-microplate was applied to detect the frequency and reactivity of Hepatitis B virus (HBV) core antigen18–27- and surface antigen183–191-specific CD8+T cells for the patients, and was compared with conventional method. This method without the need of high-end instruments may facilitate the routine analysis of patient-specific cellular immune response pattern to a given antigen in translational studies.
Microfluidic-assisted Formation of Highly Monodisperse and Mesoporous Silica Soft Microcapsules
Authors: Bchellaoui Nizar , Hayat Zain , Mami Mohamed , Dorbez-Sridi Rachida , El Abed Abdel Illah 
Published: November 2017

AbstractThe fabrication of mesoporous silica microcapsules with a highly controlled particle size ranging in the micrometer size presents a major challenge in many academic and industrial research areas, such as for the developement of smart drug delivery systems with a well controlled loading and release of (bio)active molecules. Many studies based on the solvent evaporation or solvent diffusion methods have been developed during the last two decades in order to control the particle size, which is often found to range at a sub-micrometer scale. Droplet-based microfluidics proved during the last decade a powerful tool to produce highly monodisperse and mesoporous silica solid microspheres with a controllable size in the micrometer range. We show in the present study, in contrast with previous microfluidic-assisted approaches, that a better control of the diffusion of the silica precursor sol in a surrounding perfluorinated oil phase during the silica formation process allows for the formation of highly monodisperse mesoporous silica microcapsules with a diameter ranging in the 10 micrometer range. We show also, using optical, scanning and transmission electron microscopies, small angle x-ray diffraction and BET measurements, that the synthesized mesoporous silica microcapsules exhibit a soft-like thin shell with a thickness of about 1 μm, across which 5.9 nm sized mesopores form a well-ordered hexagonal 2D network. We suggest and validate experimentally a model where the formation of such microcapsules is controlled by the solvent evaporation process at the droplet-air interface.
Characteristics of martensitic and strain-glass transitions of the Fe-substituted TiNi shape memory alloys probed by transport and thermal measurements
Authors: Ramachandran Balakrishnan , Chang Pei-Chi , Kuo Yung-Kang , Chien Chen , Wu Shyi-Kaan 
Published: November 2017

AbstractThe electrical resistivity, Seebeck coefficient, thermal conductivity, and specific heat of Ti50Ni50-x
Fe
x
(x = 2.0–10.0 at.%) shape memory alloys (SMAs) were measured to investigate the influence of point defects (Fe) on the martensitic transformation characteristics. Our results show that the Ti50Ni48Fe2 and Ti50Ni47Fe3 SMAs have a two-step martensitic transformation (B2 → R and R → B19′), while the Ti50Ni46Fe4, Ti50Ni44.5Fe5.5, and Ti50Ni44Fe6 SMAs display a one-step martensitic transition (B2 → R). However, the compounds Ti50Ni42Fe8 and Ti50Ni40Fe10 show strain glass features (frozen strain-ordered state). Importantly, the induced point defects significantly alter the martensitic transformation characteristics, namely transition temperature and width of thermal hysteresis during the transition. This can be explained by the stabilization of austenite B2 phase upon Fe substitution, which ultimately leads to the decrease in enthalpy that associated to the martensitic transition. To determine the boundary composition that separates the R-phase and strain glass systems in this series of SMAs, a Ni-rich specimen Ti49Ni45Fe6 was fabricated. Remarkably, a slight change in Ti/Ni ratio converts Ti49Ni45Fe6 SMA into a strain glass system. Overall, the evolution of phase transformation in the Fe-substituted TiNi SMAs is presumably caused by the changes in local lattice structure via the induced local strain fields by Fe point defects.