bluuebunny/crossref_metadata_2025_split huggingface dataset:
Task-induced attention load guides and gates unconscious semantic interference
Authors: Hung Shao-Min , Wu Daw-An , Shimojo Shinsuke 
Published: April 2020

AbstractThe tight relationship between attention and conscious perception has been extensively researched in the past decades. However, whether attentional modulation extended to unconscious processes remained largely unknown, particularly when it came to abstract and high-level processing. Here we use a double Stroop paradigm to demonstrate that attention load gates unconscious semantic processing. We find that word and color incongruencies between a subliminal prime and a supraliminal target cause slower responses to non-Stroop target words—but only if the task is to name the target word (low-load task), and not if the task is to name the target’s color (high-load task). The task load hypothesis is confirmed by showing that the word-induced incongruence effect can be detected in the color-naming task, but only in the late, practiced trials. We further replicate this task-induced attentional modulation phenomenon in separate experiments with colorless words (word-only) and words with semantic relationship but no orthographic similarities (semantics-only).
Seismic evidence for subduction-induced mantle flows underneath Middle America
Authors: Zhu Hejun , Stern Robert J. , Yang Jidong 
Published: April 2020

AbstractLaboratory experiments and geodynamic simulations demonstrate that poloidal- and toroidal-mode mantle flows develop around subduction zones. Here, we use a new 3-D azimuthal anisotropy model constructed by full waveform inversion, to infer deep subduction-induced mantle flows underneath Middle America. At depths shallower than 150 km, poloidal-mode flow is perpendicular to the trajectory of the Middle American Trench. From 300 to 450 km depth, return flows surround the edges of the Rivera and Atlantic slabs, while escape flows are inferred through slab windows beneath Panama and central Mexico. Furthermore, at 700 km depth, the study region is dominated by the Farallon anomaly, with fast axes perpendicular to its strike, suggesting the development of lattice-preferred orientations by substantial stress. These observations provide depth-dependent seismic anisotropy for future mantle flow simulations, and call for further investigations about the deformation mechanisms and elasticity of minerals in the transition zone and uppermost lower mantle.
Single-shot ultrafast imaging attaining 70 trillion frames per second
Authors: Wang Peng , Liang Jinyang , Wang Lihong V. 
Published: April 2020

AbstractReal-time imaging of countless femtosecond dynamics requires extreme speeds orders of magnitude beyond the limits of electronic sensors. Existing femtosecond imaging modalities either require event repetition or provide single-shot acquisition with no more than 1013 frames per second (fps) and 3 × 102 frames. Here, we report compressed ultrafast spectral photography (CUSP), which attains several new records in single-shot multi-dimensional imaging speeds. In active mode, CUSP achieves both 7 × 1013 fps and 103 frames simultaneously by synergizing spectral encoding, pulse splitting, temporal shearing, and compressed sensing—enabling unprecedented quantitative imaging of rapid nonlinear light-matter interaction. In passive mode, CUSP provides four-dimensional (4D) spectral imaging at 0.5 × 1012 fps, allowing the first single-shot spectrally resolved fluorescence lifetime imaging microscopy (SR-FLIM). As a real-time multi-dimensional imaging technology with the highest speeds and most frames, CUSP is envisioned to play instrumental roles in numerous pivotal scientific studies without the need for event repetition.
Structural basis for DNA damage-induced phosphoregulation of MDM2 RING domain
Authors: Magnussen Helge M. , Ahmed Syed F. , Sibbet Gary. J. , Hristova Ventzislava A. , Nomura Koji , Hock Andreas K. , Archibald Lewis J. , Jamieson Andrew G. , Fushman David , Vousden Karen H. , Weissman Allan M. , Huang Danny T. 
Published: April 2020

AbstractPhosphorylation of MDM2 by ATM upon DNA damage is an important mechanism for deregulating MDM2, thereby leading to p53 activation. ATM phosphorylates multiple residues near the RING domain of MDM2, but the underlying molecular basis for deregulation remains elusive. Here we show that Ser429 phosphorylation selectively enhances the ubiquitin ligase activity of MDM2 homodimer but not MDM2-MDMX heterodimer. A crystal structure of phospho-Ser429 (pS429)-MDM2 bound to E2–ubiquitin reveals a unique 310-helical feature present in MDM2 homodimer that allows pS429 to stabilize the closed E2–ubiquitin conformation and thereby enhancing ubiquitin transfer. In cells Ser429 phosphorylation increases MDM2 autoubiquitination and degradation upon DNA damage, whereas S429A substitution protects MDM2 from auto-degradation. Our results demonstrate that Ser429 phosphorylation serves as a switch to boost the activity of MDM2 homodimer and promote its self-destruction to enable rapid p53 stabilization and resolve a long-standing controversy surrounding MDM2 auto-degradation in response to DNA damage.
Intron retention is a hallmark and spliceosome represents a therapeutic vulnerability in aggressive prostate cancer
Authors: Zhang Dingxiao , Hu Qiang , Liu Xiaozhuo , Ji Yibing , Chao Hsueh-Ping , Liu Yan , Tracz Amanda , Kirk Jason , Buonamici Silvia , Zhu Ping , Wang Jianmin , Liu Song , Tang Dean G. 
Published: April 2020

AbstractThe role of dysregulation of mRNA alternative splicing (AS) in the development and progression of solid tumors remains to be defined. Here we describe the first comprehensive AS landscape in the spectrum of human prostate cancer (PCa) evolution. We find that the severity of splicing dysregulation correlates with disease progression and establish intron retention as a hallmark of PCa stemness and aggressiveness. Systematic interrogation of 274 splicing-regulatory genes (SRGs) uncovers prevalent genomic copy number variations (CNVs), leading to mis-expression of ~68% of SRGs during PCa development and progression. Consequently, many SRGs are prognostic. Surprisingly, androgen receptor controls a splicing program distinct from its transcriptional regulation. The spliceosome modulator, E7107, reverses cancer aggressiveness and inhibits castration-resistant PCa (CRPC) in xenograft and autochthonous PCa models. Altogether, our studies establish aberrant AS landscape caused by dysregulated SRGs as a hallmark of PCa aggressiveness and the spliceosome as a therapeutic vulnerability for CRPC.
Improved GPCR ligands from nanobody tethering
Authors: Cheloha Ross W. , Fischer Fabian A. , Woodham Andrew W. , Daley Eileen , Suminski Naomi , Gardella Thomas J. , Ploegh Hidde L. 
Published: April 2020

AbstractAntibodies conjugated to bioactive compounds allow targeted delivery of therapeutics to cell types of choice based on that antibody’s specificity. Here we develop a new type of conjugate that consists of a nanobody and a peptidic ligand for a G protein-coupled receptor (GPCR), fused via their C-termini. We address activation of parathyroid hormone receptor-1 (PTHR1) and improve the signaling activity and specificity of otherwise poorly active N-terminal peptide fragments of PTH by conjugating them to nanobodies (VHHs) that recognize PTHR1. These C-to-C conjugates show biological activity superior to that of the parent fragment peptide in vitro. In an exploratory experiment in mice, a VHH-PTH peptide conjugate showed biological activity, whereas the corresponding free peptide did not. The lead conjugate also possesses selectivity for PTHR1 superior to that of PTH(1-34). This design approach, dubbed “conjugation of ligands and antibodies for membrane proteins” (CLAMP), can yield ligands with high potency and specificity.
Myosin-VIIa is expressed in multiple isoforms and essential for tensioning the hair cell mechanotransduction complex
Authors: Li Sihan , Mecca Andrew , Kim Jeewoo , Caprara Giusy A. , Wagner Elizabeth L. , Du Ting-Ting , Petrov Leonid , Xu Wenhao , Cui Runjia , Rebustini Ivan T. , Kachar Bechara , Peng Anthony W. , Shin Jung-Bum 
Published: April 2020

AbstractMutations in myosin-VIIa (MYO7A) cause Usher syndrome type 1, characterized by combined deafness and blindness. MYO7A is proposed to function as a motor that tensions the hair cell mechanotransduction (MET) complex, but conclusive evidence is lacking. Here we report that multiple MYO7A isoforms are expressed in the mouse cochlea. In mice with a specific deletion of the canonical isoform (Myo7a-ΔC mouse), MYO7A is severely diminished in inner hair cells (IHCs), while expression in outer hair cells is affected tonotopically. IHCs of Myo7a-ΔC mice undergo normal development, but exhibit reduced resting open probability and slowed onset of MET currents, consistent with MYO7A’s proposed role in tensioning the tip link. Mature IHCs of Myo7a-ΔC mice degenerate over time, giving rise to progressive hearing loss. Taken together, our study reveals an unexpected isoform diversity of MYO7A expression in the cochlea and highlights MYO7A’s essential role in tensioning the hair cell MET complex.
Super-tough MXene-functionalized graphene sheets
Authors: Zhou Tianzhu , Wu Chao , Wang Yanlei , Tomsia Antoni P. , Li Mingzhu , Saiz Eduardo , Fang Shaoli , Baughman Ray H. , Jiang Lei , Cheng Qunfeng 
Published: April 2020

AbstractFlexible reduced graphene oxide (rGO) sheets are being considered for applications in portable electrical devices and flexible energy storage systems. However, the poor mechanical properties and electrical conductivities of rGO sheets are limiting factors for the development of such devices. Here we use MXene (M) nanosheets to functionalize graphene oxide platelets through Ti-O-C covalent bonding to obtain MrGO sheets. A MrGO sheet was crosslinked by a conjugated molecule (1-aminopyrene-disuccinimidyl suberate, AD). The incorporation of MXene nanosheets and AD molecules reduces the voids within the graphene sheet and improves the alignment of graphene platelets, resulting in much higher compactness and high toughness. In situ Raman spectroscopy and molecular dynamics simulations reveal the synergistic interfacial interaction mechanisms of Ti-O-C covalent bonding, sliding of MXene nanosheets, and π-π bridging. Furthermore, a supercapacitor based on our super-tough MXene-functionalized graphene sheets provides a combination of energy and power densities that are high for flexible supercapacitors.
Arctic avian predators synchronise their spring migration with the northern progression of snowmelt
Authors: Curk Teja , Pokrovsky Ivan , Lecomte Nicolas , Aarvak Tomas , Brinker David F. , Burnham Kurt , Dietz Andreas , Dixon Andrew , Franke Alastair , Gauthier Gilles , Jacobsen Karl-Otto , Kidd Jeff , Lewis Stephen B. , Øien Ingar J. , Sokolov Aleksandr , Sokolov Vasiliy , Solheim Roar , Weidensaul Scott , Wiebe Karen , Wikelski Martin , Therrien Jean-François , Safi Kamran 
Published: April 2020

AbstractMigratory species display a range of migration patterns between irruptive (facultative) to regular (obligate), as a response to different predictability of resources. In the Arctic, snow directly influences resource availability. The causes and consequences of different migration patterns of migratory species as a response to the snow conditions remains however unexplored. Birds migrating to the Arctic are expected to follow the spring snowmelt to optimise their arrival time and select for snow-free areas to maximise prey encounter en-route. Based on large-scale movement data, we compared the migration patterns of three top predator species of the tundra in relation to the spatio-temporal dynamics of snow cover. The snowy owl, an irruptive migrant, the rough-legged buzzard, with an intermediary migration pattern, and the peregrine falcon as a regular migrant, all followed, as expected, the spring snowmelt during their migrations. However, the owl stayed ahead, the buzzard stayed on, and the falcon stayed behind the spatio-temporal peak in snowmelt. Although none of the species avoided snow-covered areas, they presumably used snow presence as a cue to time their arrival at their breeding grounds. We show the importance of environmental cues for species with different migration patterns.
Real-time detection and identification of nematode eggs genus and species through optical imaging
Authors: Qazi Farah , Khalid Asma , Poddar Arpita , Tetienne Jean-Philippe , Nadarajah Athavan , Aburto-Medina Arturo , Shahsavari Esmaeil , Shukla Ravi , Prawer Steven , Ball Andrew S. , Tomljenovic-Hanic Snjezana 
Published: April 2020

AbstractNematode eggs are pervasive pathogens that infect billions of people and livestock every year. Adult parasitic nematode worms can be distinguished based on their size and morphology. However, their eggs, particularly their species Ascaris lumbricoides and Ascaris suum cannot be identified from each other. Identifying eggs of helminths from wastewater and sludge is important from a public health perspective to minimize the spread of Ascaris infections. Numerous methods exist for nematode identification, from a morphological-based approach to high throughput sequencing technology. However, these techniques are not consistent and often laborious and time-consuming. In this study, we demonstrate that non-invasive real-time identification of eggs is possible based on their intrinsic fluorescence. Using confocal microscopy, we investigate the autofluorescence properties of five species of nematode eggs and observe clear differences between genus and for the first time their species in sludge samples. This non-invasive imaging technique could lead to better understanding of these species and may assist in early control of diseases.
A Self-Assembling Lipidic Peptide and Selective Partial V2 Receptor Agonist Inhibits Urine Production
Authors: Patel Sunish , Volpe Antonella Bavuso , Awwad Sahar , Schätzlein Andreas G. , Haider Shozeb , Liu Boqian , Uchegbu Ijeoma F. 
Published: April 2020

AbstractLipidised analgesic peptide prodrugs self-assemble into peptide nanofibers; with the nanofiber morphology protecting the peptide from plasma degradation and improving therapeutic efficacy. Extending this learning, we hypothesised that a self-assembling lipidized peptide arginine vasopressin (AVP) receptor agonist, that had not been designed as a prodrug, could prove pharmacologically active and control urine production. The only approved AVP receptor agonist, desmopressin is indicated for the treatment of central diabetes insipidus (DI), bedwetting, haemophilia A and von Willebrand disease. Desmopressin is well tolerated by most patients, however adverse effects, such as hyponatraemia and water intoxication necessitate a strict fluid intake, thus motivating the search for alternative DI treatments. Selective V2 receptor agonism is required for anti-DI activity and we hypothesised that our new lipidized peptide (METx) would lead to selective AVP receptor agonism. METx was synthesised and characterised and then tested for activity against the V2, V1a and OT uterine receptors and not tested against the V1b receptor as METx was not expected to cross the blood brain barrier. METx was also tested in vivo in a healthy rat model. METx forms nanofibers and is a partial V2 receptor agonist (determined by measuring MDCK cell line cAMP accumulation), producing 57% of AVP’s maximal activity (EC50 = 2.7 nM) and is not a V1a agonist up to a concentration of 1 μM (determined by measuring A7r5 cell line D-myo-inositol-1-phosphate accumulation). METx is a weak OT receptor antagonist, reducing the frequency of OT induced contractions (EC50 = 350 nM) and increasing the OT EC50 from 0.081 nM to 21 nM at a concentration of 600 nM. METx (41 nM) had no effect on spontaneous uterine contractions and METx (100 nM) had no effect on OT induced uterine contractions. Simulated binding studies show that binding avidity to the receptors follows the trend: V2 > OT > V1a. On intravenous injection, a nanoparticle formulation of METx reduced urine production in a healthy rat model in a dose responsive manner, with 40 mg kg−1 METx resulting in no urine production over 4 hours. The lipidized self-assembling peptide – METx - is a selective competitive V2 receptor agonist and an anti-diuretic.
N-glycosylation of α1D-adrenergic receptor N-terminal domain is required for correct trafficking, function, and biogenesis
Authors: Janezic Eric M. , Lauer Sophia My-Linh , Williams Robert George , Chungyoun Michael , Lee Kyung-Soon , Navaluna Edelmar , Lau Ho-Tak , Ong Shao-En , Hague Chris 
Published: April 2020

AbstractG protein-coupled receptor (GPCR) biogenesis, trafficking, and function are regulated by post-translational modifications, includingN-glycosylation of asparagine residues. α1D-adrenergic receptors (α1D-ARs) – key regulators of central and autonomic nervous system function – contain two putativeN-glycosylation sites within the large N-terminal domain at N65 and N82. However, determining the glycosylation state of this receptor has proven challenging. Towards understanding the role of these putative glycosylation sites, site-directed mutagenesis and lectin affinity purification identified N65 and N82 asbona fideacceptors forN-glycans. Surprisingly, we also report that simultaneously mutating N65 and N82 causes early termination of α1D-AR between transmembrane domain 2 and 3. Label-free dynamic mass redistribution and cell surface trafficking assays revealed that single and double glycosylation deficient mutants display limited function with impaired plasma membrane expression. Confocal microscopy imaging analysis and SNAP-tag sucrose density fractionation assays revealed the dual glycosylation mutant α1D-AR is widely distributed throughout the cytosol and nucleus. Based on these novel findings, we propose α1D-AR transmembrane domain 2 acts as an ER localization signal during active protein biogenesis, and that α1D-AR N-terminal glycosylation is required for complete translation of nascent, functional receptor.
Transcutaneous Electrical Nerve Stimulation Improves Stair Climbing Capacity in People with Knee Osteoarthritis
Authors: Iijima Hirotaka , Eguchi Ryo , Shimoura Kanako , Yamada Keisuke , Aoyama Tomoki , Takahashi Masaki 
Published: April 2020

AbstractThis study aimed to examine the effect of transcutaneous electrical nerve stimulation (TENS) on stair climbing capacity in individuals with pre-radiographic to mild knee osteoarthritis (OA). This is a secondary analysis of data from a single, participant-blinded, randomized controlled trial with a pre-post design. Participants with pre-radiographic to mild knee OA (mean age, 59.1 years; 72.9% women) were randomly assigned into two groups, a TENS (n = 30) and a sham-TENS groups (n = 29). TENS or sham-TENS treatments were applied to all participants by using the prototype TENS device with pre-specified parameters. The primary outcome measures included valid and reliable functional measures for stair climbing (stair-climb test [SCT]), visual analog scale for knee pain during the SCT, and quadriceps muscle strength. TENS improved SCT time by 0.41 s (95% confidence interval [CI]: 0.07, 0.75). The time reduction in the transition phase explains the TENS therapeutic effect. Post-hoc correlation analyses revealed a non-significant but positive relationship between the pain relief effect and improved 11-step SCT time in the TENS group but not in the sham-TENS group. These results indicate that the TENS intervention may be an option for reducing the burden of early-stage knee OA.
Behavioral and neuronal study of inhibition of return in barn owls
Authors: Lev-Ari Tidhar , Zahar Yael , Agarwal Arpit , Gutfreund Yoram 
Published: April 2020

AbstractInhibition of return (IOR) is the reduction of detection speed and/or detection accuracy of a target in a recently attended location. This phenomenon, which has been discovered and studied thoroughly in humans, is believed to reflect a brain mechanism for controlling the allocation of spatial attention in a manner that enhances efficient search. Findings showing that IOR is robust, apparent at a very early age and seemingly dependent on midbrain activity suggest that IOR is a universal attentional mechanism in vertebrates. However, studies in non-mammalian species are scarce. To explore this hypothesis comparatively, we tested for IOR in barn owls (Tyto alba) using the classical Posner cueing paradigm. Two barn owls were trained to initiate a trial by fixating on the center of a computer screen and then turning their gaze to the location of a target. A short, non-informative cue appeared before the target, either at a location predicting the target (valid) or a location not predicting the target (invalid). In one barn owl, the response times (RT) to the valid targets compared to the invalid targets shifted from facilitation (lower RTs) to inhibition (higher RTs) when increasing the time lag between the cue and the target. The second owl mostly failed to maintain fixation and responded to the cue before the target onset. However, when including in the analysis only the trials in which the owl maintained fixation, an inhibition in the valid trials could be detected. To search for the neural correlates of IOR, we recorded multiunit responses in the optic tectum (OT) of four head-fixed owls passively viewing a cueing paradigm as in the behavioral experiments. At short cue to target lags (<100 ms), neural responses to the target in the receptive field (RF) were usually enhanced if the cue appeared earlier inside the RF (valid) and were suppressed if the cue appeared earlier outside the RF (invalid). This was reversed at longer lags: neural responses were suppressed in the valid conditions and were unaffected in the invalid conditions. The findings support the notion that IOR is a basic mechanism in the evolution of vertebrate behavior and suggest that the effect appears as a result of the interaction between lateral and forward inhibition in the tectal circuitry.