bluuebunny/crossref_metadata_2025_split huggingface dataset:
Highly sensitive dual mode electrochemical platform for microRNA detection
Authors: Jolly Pawan , Batistuti Marina R. , Miodek Anna , Zhurauski Pavel , Mulato Marcelo , Lindsay Mark A. , Estrela Pedro 
Published: November 2016

AbstractMicroRNAs (miRNAs) play crucial regulatory roles in various human diseases including cancer, making them promising biomarkers. However, given the low levels of miRNAs present in blood, their use as cancer biomarkers requires the development of simple and effective analytical methods. Herein, we report the development of a highly sensitive dual mode electrochemical platform for the detection of microRNAs. The platform was developed using peptide nucleic acids as probes on gold electrode surfaces to capture target miRNAs. A simple amplification strategy using gold nanoparticles has been employed exploiting the inherent charges of the nucleic acids. Electrochemical impedance spectroscopy was used to monitor the changes in capacitance upon any binding event, without the need for any redox markers. By using thiolated ferrocene, a complementary detection mode on the same sensor was developed where the increasing peaks of ferrocene were recorded using square wave voltammetry with increasing miRNA concentration. This dual-mode approach allows detection of miRNA with a limit of detection of 0.37 fM and a wide dynamic range from 1 fM to 100 nM along with clear distinction from mismatched target miRNA sequences. The electrochemical platform developed can be easily expanded to other miRNA/DNA detection along with the development of microarray platforms.
B7-H1 antibodies lose antitumor activity due to activation of p38 MAPK that leads to apoptosis of tumor-reactive CD8+ T cells
Authors: Liu Xin , Wu Xiaosheng , Cao Siyu , Harrington Susan M. , Yin Peng , Mansfield Aaron S. , Dong Haidong 
Published: November 2016

AbstractB7-H1 (aka PD-L1) blocking antibodies have been used in treatment of human cancers through blocking B7-H1 expressed by tumor cells; however, their impact on B7-H1 expressing tumor-reactive CD8+ T cells is still unknown. Here, we report that tumor-reactive CD8+ T cells expressing B7-H1 are functional effector cells. In contrast to normal B7-H1 blocking antibody, B7-H1 antibodies capable of activating p38 MAPK lose their antitumor activity by deleting B7-H1+ tumor-reactive CD8+ T cells via p38 MAPK pathway. B7-H1 deficiency or engagement with certain antibody results in more activation of p38 MAPK that leads to T cell apoptosis. DNA-PKcs is a new intracellular partner of B7-H1 in the cytoplasm of activated CD8+ T cells. B7-H1 suppresses p38 MAPK activation by sequestering DNA-PKcs in order to preserve T cell survival. Our findings provide a new mechanism of action of B7-H1 in T cells and have clinical implications in cancer immunotherapy when anti-B7-H1 (PD-L1) antibody is applied.
Effect of p22phox depletion on sympathetic regulation of blood pressure in SHRSP: evaluation in a new congenic strain
Authors: Zahid Hasan M. , Ferdaus Mohammed Zubaerul , Ohara Hiroki , Isomura Minoru , Nabika Toru 
Published: November 2016

AbstractOxidative stress in the rostral ventrolateral medulla (RVLM), a sympathetic center in the brainstem, was implicated in the regulation of sympathetic activity in various hypertensive models including stroke-prone spontaneously hypertensive rats (SHRSP). In this study, we evaluated the role of the NADPH oxidases (NOX) in the blood pressure (BP) regulation in RVLM in SHRSP. The P22PHOX-depleted congenic SHRSP (called SP.MES) was constructed by introducing the mutated p22phox gene of Matsumoto Eosinophilic Shinshu rat. BP response to glutamate (Glu) microinjection into RVLM was compared among SHRSP, SP.MES, SHR and Wistar Kyoto (WKY); the response to Glu microinjection was significantly greater in SHRSP than in SP.MES, SHR and WKY. In addition, tempol, losartan and apocynin microinjection reduced the response to Glu significantly only in SHRSP. The level of oxidative stress, measured in the brainstem using lucigenin and dihydroethidium, was reduced in SP.MES than in SHRSP. BP response to cold stress measured by telemetry system was also blunted in SP.MES when compared with SHRSP. The results suggested that oxidative stress due to the NOX activation in RVLM potentiated BP response to Glu in SHRSP, which might contribute to the exaggerated response to stress in this strain.
High-field magnetic resonance imaging of structural alterations in first-episode, drug-naive patients with major depressive disorder
Authors: Chen Z , Peng W , Sun H , Kuang W , Li W , Jia Z , Gong Q 
Published: November 2016

AbstractPrevious structural imaging studies have found evidence of brain morphometric changes in patients with major depressive disorder (MDD), but these studies rarely excluded compounding effects of certain important factors, such as medications and long duration of illnesses. Furthermore, the neurobiological mechanism of the macroscopic findings of structural alterations in MDD patients remains unclear. In this study, we utilized magnetization transfer imaging, a quantitative measure of the macromolecular structural integrity of brain tissue, to identify biophysical alterations, which are represented by a magnetization transfer ratio (MTR), in MDD patients. To ascertain whether MTR changes occur independent of volume loss, we also conduct voxel-based morphometry (VBM) analysis. The participants included 27 first-episode, drug-naive MDD patients and 28 healthy controls matched for age and gender. Whole-brain voxel-based analysis was used to compare MTR and gray matter volume across groups and to analyse correlations between MTR and age, symptom severity, and illness duration. The patients exhibited significantly lower MTR in the left superior parietal lobule and left middle occipital gyrus compared with healthy controls, which may be related to the attentional and cognitive dysfunction in MDD patients. The VBM analysis revealed significantly increased gray matter volume in right postcentral gyrus in MDD patients. These findings in first-episode, drug-naive MDD patients may reflect microstructural gray matter changes in the parietal and occipital cortices close to illness onset that existed before volume loss, and thus potentially provide important new insight into the early neurobiology of depression.
Ankyrin-3 as a molecular marker of early-life stress and vulnerability to psychiatric disorders
Authors: Luoni A , Massart R , Nieratschker V , Nemoda Z , Blasi G , Gilles M , Witt S H , Suderman M J , Suomi S J , Porcelli A , Rizzo G , Fazio L , Torretta S , Rampino A , Berry A , Gass P , Cirulli F , Rietschel M , Bertolino A , Deuschle M , Szyf M , Riva M A 
Published: November 2016

AbstractExposure to early-life stress (ELS) may heighten the risk for psychopathology at adulthood. Here, in order to identify common genes that may keep the memory of ELS through changes in their methylation status, we intersected methylome analyses performed in different tissues and time points in rats, non-human primates and humans, all characterized by ELS. We identified Ankyrin-3 (Ank3), a scaffolding protein with a strong genetic association for psychiatric disorders, as a gene persistently affected by stress exposure. In rats, Ank3 methylation and mRNA changes displayed a specific temporal profile during the postnatal development. Moreover, exposure to prenatal stress altered the interaction of ankyrin-G, the protein encoded by Ank3 enriched in the post-synaptic compartment, with PSD95. Notably, to model in humans a gene by early stress interplay on brain phenotypes during cognitive performance, we demonstrated an interaction between functional variation in Ank3 gene and obstetric complications on working memory in healthy adult subjects. Our data suggest that alterations of Ank3 expression and function may contribute to the effects of ELS on the development of psychiatric disorders.
You say ‘prefrontal cortex’ and I say ‘anterior cingulate’: meta-analysis of spatial overlap in amygdala-to-prefrontal connectivity and internalizing symptomology
Authors: Marusak H A , Thomason M E , Peters C , Zundel C , Elrahal F , Rabinak C A 
Published: November 2016

AbstractConnections between the amygdala and medial prefrontal cortex (mPFC) are considered critical for the expression and regulation of emotional behavior. Abnormalities in frontoamygdala circuitry are reported across several internalizing conditions and associated risk factors (for example, childhood trauma), which may underlie the strong phenotypic overlap and co-occurrence of internalizing conditions. However, it is unclear if these findings converge on the same localized areas of mPFC or adjacent anterior cingulate cortex (ACC). Examining 46 resting-state functional connectivity magnetic resonance imaging studies of internalizing conditions or risk factors (for example, early adversity and family history), we conducted an activation likelihood estimation meta-analysis of frontoamygdala circuitry. We included all reported amygdala to frontal coordinate locations that fell within a liberal anatomically defined frontal mask. Peak effects across studies were centered in two focal subareas of the ACC: pregenual (pgACC) and subgenual (sgACC). Using publicly available maps and databases of healthy individuals, we found that observed subareas have unique connectivity profiles, patterns of neural co-activation across a range of neuropsychological tasks, and distribution of tasks spanning various behavioral domains within peak regions, also known as ‘functional fingerprints’. These results suggest disruptions in unique amygdala–ACC subcircuits across internalizing, genetic and environmental risk studies. Based on functional characterizations and the studies contributing to each peak, observed amygdala–ACC subcircuits may reflect separate transdiagnostic neural signatures. In particular, they may reflect common neurobiological substrates involved in developmental risk (sgACC), or the broad expression of emotional psychopathology (pgACC) across disease boundaries.
Association of ATP6V1B2 rs1106634 with lifetime risk of depression and hippocampal neurocognitive deficits: possible novel mechanisms in the etiopathology of depression
Authors: Gonda X , Eszlari N , Anderson I M , Deakin J F W , Bagdy G , Juhasz G 
Published: November 2016

AbstractCurrent understanding and treatment of depression is limited to the monoaminergic theory with little knowledge of the involvement of other cellular processes. Genome-wide association studies, however, implicate several novel single-nucleotide polymorphisms with weak but replicable effects and unclarified mechanisms. We investigated the effect of rs1106634 of the ATPV1B2 gene encoding the vacuolar H+ATPase on lifetime and current depression and the possible mediating role of neuroticism by logistic and linear regression in a white European general sample of 2226 subjects. Association of rs1106634 with performance on frontal (Stockings of Cambridge (SOC)) and hippocampal-dependent (paired associates learning (PAL)) cognitive tasks was investigated in multivariate general linear models in a smaller subsample. The ATP6V1B2 rs1106634 A allele had a significant effect on lifetime but not on current depression. The effect of the A allele on lifetime depression was not mediated by neuroticism. The A allele influenced performance on the PAL but not on the SOC test. We conclude that the effects of variation in the vacuolar ATPase may point to a new molecular mechanism that influences the long-term development of depression. This mechanism may involve dysfunction specifically in hippocampal circuitry and cognitive impairment that characterizes recurrent and chronic depression.
Coupling light into organic nanofibres via Raman scattering: waveguiding properties for near‐infrared light
Authors: Takazawa Ken 
Published: November 2016

A technique to couple near‐infrared (IR) light into organic nanofibres that function as active optical waveguides by utilising Raman scattering is developed. Using this technique, light was coupled with λ = 800–910 nm into an organic nanofibre of thiacyanine (TC) dye and waveguiding properties in this wavelength range were investigated. A number of organic nanofibres, including TC nanofibres, have been found to function as active waveguides that propagate their own fluorescence along themselves. The waveguiding properties of these nanofibres have been extensively investigated in their fluorescence wavelength range, which is usually in the ultraviolet to visible region. However, their waveguiding properties outside of the fluorescence range are completely unknown because of the difficulties in coupling light from an external light source. The technique enables coupling of light with various wavelengths from the visible to the near‐IR into nanofibre waveguides and investigation of the waveguiding properties at these wavelengths.
Supercritical entanglement in local systems: Counterexample to the area law for quantum matter
Authors: Movassagh Ramis , Shor Peter W. 
Published: November 2016

SignificanceWe introduce a class of exactly solvable models with surprising properties. We show that even simple quantum matter is much more entangled than previously believed possible. One then expects more complex systems to be substantially more entangled. For over two decades it was believed that the area law is violated by at most a logarithm in the system’s size for quantum matter (i.e., interactions satisfying physical reasonability criteria clearly stated in the article). In this work we introduce a class of physically reasonable models that we can prove violate the area law by a square root, i.e., exponentially more than the logarithm.
Siderophore vaccine conjugates protect against uropathogenicEscherichia coliurinary tract infection
Authors: Mike Laura A. , Smith Sara N. , Sumner Christopher A. , Eaton Kathryn A. , Mobley Harry L. T. 
Published: November 2016

SignificanceUrinary tract infections (UTIs) are primarily caused by uropathogenicEscherichia coli(UPEC), and 1 in 40 women experience chronic UTIs during their lifetime. The antibiotic courses required to treat infections promote antibiotic resistance, and current vaccine options offer limited protection. We have pioneered a strategy using small iron-chelating compounds called siderophores as vaccine antigens. These siderophores are not produced by commensal bacteria and are required for UTI. The siderophore vaccines reported here are easy to formulate and reduce bacterial burdens in a murine model of UTI. This report highlights the untapped resource of bacteria-specific small molecules as potential vaccine antigens and provides a proof of principle for incorporating these compounds into multicomponent vaccines for the prevention of bacterial infections.
IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy
Authors: Liu Boyi , Tai Yan , Achanta Satyanarayana , Kaelberer Melanie M. , Caceres Ana I. , Shao Xiaomei , Fang Jianqiao , Jordt Sven-Eric 
Published: November 2016

Significance
In the United States, the most common cause of allergic contact dermatitis (ACD) is contact with poison ivy. Severe itch and skin inflammation are the major manifestations of poison ivy-induced ACD. In this study, we have established a critical role of IL-33/ST2 (interleukin 33/growth stimulation expressed gene 2) signaling in both itch and skin inflammation of poison ivy-induced ACD and revealed a previously unidentified interaction of IL-33/ST2 signaling with primary sensory neurons that may underlie the pruritic mechanisms of poison ivy-induced ACD. Blocking IL-33/ST2 signaling may represent a therapeutic approach to ameliorate itch and skin inflammation related to poison ivy dermatitis and, possibly, other chronic itch conditions in which IL-33/ST2 signaling may participate.
Ultrahigh-throughput–directed enzyme evolution by absorbance-activated droplet sorting (AADS)
Authors: Gielen Fabrice , Hours Raphaelle , Emond Stephane , Fischlechner Martin , Schell Ursula , Hollfelder Florian 
Published: November 2016

Significance
Directed enzyme evolution is a powerful approach for discovering new catalysts with applications in green chemistry and elsewhere. However, “hits” in sequence space are rare: If too few members of a library are examined, the chances of success of a campaign are limited. Ultrahigh-throughput screening in emulsion droplets has dramatically increased the odds but requires a fluorescent reaction product that triggers selection of hits. We now introduce an absorbance-based microfluidic droplet sorter that broadens the scope of assays to those producing UV/Vis-active chromophores and demonstrate its usefulness by evolving a dehydrogenase based on the screening of half a million library members. Making ultrahigh-throughput screening possible for previously inaccessible reactions enables much wider use of microfluidic droplet sorters for laboratory evolution.
Accelerated search for BaTiO
3
-based piezoelectrics with vertical morphotropic phase boundary using Bayesian learning
Authors: Xue Dezhen , Balachandran Prasanna V. , Yuan Ruihao , Hu Tao , Qian Xiaoning , Dougherty Edward R. , Lookman Turab 
Published: November 2016

Significance
Learning from data to accelerate the discovery of new materials is an outstanding challenge in materials science. However, in addition to data, a distinguishing aspect of materials science is that there exists a substantial body of knowledge in the form of phenomenological models and physical theories. We combine informatics and materials knowledge using results from Landau–Devonshire theory to guide experiments in the design of lead-free piezoelectrics with desired properties.
Selective nucleolus organizer inactivation in
Arabidopsis
is a chromosome position-effect phenomenon
Authors: Mohannath Gireesha , Pontvianne Frederic , Pikaard Craig S. 
Published: November 2016

Significance
For decades, rRNA genes have been known to be differentially regulated during growth and development, with some genes being expressed and other genes being inactive. However, rRNA genes are so similar in sequence that the basis for choosing among them to differentially express some, but not others, has long been a puzzle. This study demonstrates that entire clusters of rRNA genes, known as nucleolus organizer regions, are silenced based on the chromosome on which they reside.
Rapid conversion of an oceanic spreading center to a subduction zone inferred from high-precision geochronology
Authors: Keenan Timothy E. , Encarnación John , Buchwaldt Robert , Fernandez Dan , Mattinson James , Rasoazanamparany Christine , Luetkemeyer P. Benjamin 
Published: November 2016

Significance
Subduction, the process by which tectonic plates sink into the mantle, is a fundamental tectonic process on Earth, yet the question of where and how new subduction zones form remains a matter of debate. In this study, we find that a divergent plate boundary, where two plates move apart, was forcefully and rapidly turned into a convergent boundary where one plate eventually began subducting. This finding is surprising because, although the plate material at a divergent boundary is weak, it is also buoyant and resists subduction. This study suggests that buoyant, but weak, plate material at a divergent boundary can be forced to converge until eventually older and denser plate material enters the nascent subduction zone, which then becomes self-sustaining.
ADiaphanous-related formin links Ras signaling directly to actin assembly in macropinocytosis and phagocytosis
Authors: Junemann Alexander , Filić Vedrana , Winterhoff Moritz , Nordholz Benjamin , Litschko Christof , Schwellenbach Helena , Stephan Till , Weber Igor , Faix Jan 
Published: November 2016

SignificanceMacropinocytosis and phagocytosis are two Ras-regulated, highly related processes of great physiological relevance collectively termed large-scale endocytosis. Both are actin-driven and entail engulfment of extracellular material by crown-like protrusions. Aside from the Arp2/3 complex, which serves as the main nucleator of branched actin filaments at the cup rim, the underlying mechanisms of actin assembly still remain elusive. Here, we analyzed the role ofDiaphanous-related formin G (ForG) fromDictyosteliumby biochemical, genetic, and imaging techniques. Our data demonstrate that this formin exhibits a rather weak nucleation activity and imply that ForG-mediated filament elongation synergizes with the Arp2/3 complex in actin assembly. Finally, we identify ForG as a Ras-regulated formin and show its significance for actin assembly in endocytic structures.
Spatial variability in tree regeneration after wildfire delays and dampens future bark beetle outbreaks
Authors: Seidl Rupert , Donato Daniel C. , Raffa Kenneth F. , Turner Monica G. 
Published: November 2016

SignificanceWildfires have increased in western North America, creating extensive areas of regenerating forests. There is concern that recent large, stand-replacing fires will synchronize forest development and commit landscapes to a future of increased disturbance, such as bark beetle outbreaks that require extensive, well-connected forests of large host trees. We analyzed forest development after large high-severity 1988 fires in Yellowstone National Park to assess future susceptibility to bark beetle outbreak. Although stands originated from the same event, persistent variation in postfire tree density and size protracted the onset of susceptibility to bark beetle attack among stands. Furthermore, postfire variability delayed emergence of the habitat connectivity required for broad-scale outbreaks, suggesting spatial variability is an important dampening mechanism for disturbance interactions.
Autobiographical memory, future imagining, and the medial temporal lobe
Authors: Dede Adam J. O. , Wixted John T. , Hopkins Ramona O. , Squire Larry R. 
Published: November 2016

Significance
We explored the role of the medial temporal lobe (MTL) in autobiographical remembering and future imagining. Patients with MTL damage and controls produced narratives in four time periods (past and future). Findings showed that anterograde amnesia (forgetfulness) can interfere with narrative construction. Under conditions that minimized the effect of anterograde amnesia, patients produced as many details as controls in five different content categories (spatial and nonspatial) and in all time periods except the recent past. The results suggest that remembering the remote past and imagining the future are independent of the MTL. Comparisons among studies suggest that differences in performance likely depend on differences in the locus and extent of brain damage.
One low-dose exposure of gold nanoparticles induces long-term changes in human cells
Authors: Falagan-Lotsch Priscila , Grzincic Elissa M. , Murphy Catherine J. 
Published: November 2016

Significance
Gold nanoparticles are promising candidates for optical sensing, bioimaging, delivery, and therapeutic applications due to their size- and shape-dependent physical properties and inherent biocompatibility compared with other metallic nanoparticles. Many studies have found that these particles are generally nontoxic at low doses for most, but not all, initial surface treatments. In this study, a long-term (20 wk) exposure of a set of gold nanoparticles to a human cell line was performed in two ways: an acute burst of nanoparticle exposure compared with a continuous, chronic exposure at the same concentration. Overall, it was found that an acute burst of exposure is more harmful to cells, and that cells can adapt to long-term nanoparticle exposure.