bluuebunny/crossref_metadata_2025_split huggingface dataset:
A slowly cleaved viral signal peptide acts as a protein-integral immune evasion domain
Authors: Seidel Einat , Dassa Liat , Kahlon Shira , Tirosh Boaz , Halenius Anne , Seidel Malkinson Tal , Mandelboim Ofer 
Published: April 2021

AbstractStress can induce cell surface expression of MHC-like ligands, including MICA, that activate NK cells. Human cytomegalovirus (HCMV) glycoprotein US9 downregulates the activating immune ligand MICA*008 to avoid NK cell activation, but the underlying mechanism remains unclear. Here, we show that the N-terminal signal peptide is the major US9 functional domain targeting MICA*008 to proteasomal degradation. The US9 signal peptide is cleaved with unusually slow kinetics and this transiently retained signal peptide arrests MICA*008 maturation in the endoplasmic reticulum (ER), and indirectly induces its degradation via the ER quality control system and the SEL1L-HRD1 complex. We further identify an accessory, signal peptide-independent US9 mechanism that directly binds MICA*008 and SEL1L. Collectively, we describe a dual-targeting immunoevasin, demonstrating that signal peptides can function as protein-integral effector domains.
Neuroimaging evidence for a network sampling theory of individual differences in human intelligence test performance
Authors: Soreq Eyal , Violante Ines R. , Daws Richard E. , Hampshire Adam 
Published: April 2021

AbstractDespite a century of research, it remains unclear whether human intelligence should be studied as one dominant, several major, or many distinct abilities, and how such abilities relate to the functional organisation of the brain. Here, we combine psychometric and machine learning methods to examine in a data-driven manner how factor structure and individual variability in cognitive-task performance relate to dynamic-network connectomics. We report that 12 sub-tasks from an established intelligence test can be accurately multi-way classified (74%, chance 8.3%) based on the network states that they evoke. The proximities of the tasks in behavioural-psychometric space correlate with the similarities of their network states. Furthermore, the network states were more accurately classified for higher relative to lower performing individuals. These results suggest that the human brain uses a high-dimensional network-sampling mechanism to flexibly code for diverse cognitive tasks. Population variability in intelligence test performance relates to the fidelity of expression of these task-optimised network states.
Thiazoline-related innate fear stimuli orchestrate hypothermia and anti-hypoxia via sensory TRPA1 activation
Authors: Matsuo Tomohiko , Isosaka Tomoko , Hayashi Yuichiro , Tang Lijun , Doi Akihiro , Yasuda Aiko , Hayashi Mikio , Lee Chia-Ying , Cao Liqin , Kutsuna Natsumaro , Matsunaga Sachihiro , Matsuda Takeshi , Yao Ikuko , Setou Mitsuyoshi , Kanagawa Dai , Higasa Koichiro , Ikawa Masahito , Liu Qinghua , Kobayakawa Reiko , Kobayakawa Ko 
Published: April 2021

AbstractThiazoline-related innate fear-eliciting compounds (tFOs) orchestrate hypothermia, hypometabolism, and anti-hypoxia, which enable survival in lethal hypoxic conditions. Here, we show that most of these effects are severely attenuated in transient receptor potential ankyrin 1 (Trpa1) knockout mice. TFO-induced hypothermia involves theTrpa1-mediated trigeminal/vagal pathways and non-Trpa1olfactory pathway. TFOs activateTrpa1-positive sensory pathways projecting from trigeminal and vagal ganglia to the spinal trigeminal nucleus (Sp5) and nucleus of the solitary tract (NTS), and their artificial activation induces hypothermia. TFO presentation activates the NTS-Parabrachial nucleus pathway to induce hypothermia and hypometabolism; this activation was suppressed inTrpa1knockout mice. TRPA1 activation is insufficient to trigger tFO-mediated anti-hypoxic effects; Sp5/NTS activation is also necessary. Accordingly, we find a novel molecule that enables mice to survive in a lethal hypoxic condition ten times longer than known tFOs. Combinations of appropriate tFOs and TRPA1 command intrinsic physiological responses relevant to survival fate.
Proteasomal degradation of the tumour suppressor FBW7 requires branched ubiquitylation by TRIP12
Authors: Khan Omar M. , Almagro Jorge , Nelson Jessica K. , Horswell Stuart , Encheva Vesela , Keyan Kripa S. , Clurman Bruce E. , Snijders Ambrosius P. , Behrens Axel 
Published: April 2021

AbstractThe tumour suppressor FBW7 is a substrate adaptor for the E3 ubiquitin ligase complex SKP1-CUL1-F-box (SCF), that targets several oncoproteins for proteasomal degradation. FBW7 is widely mutated and FBW7 protein levels are commonly downregulated in cancer. Here, using an shRNA library screen, we identify the HECT-domain E3 ubiquitin ligase TRIP12 as a negative regulator of FBW7 stability. We find that SCFFBW7-mediated ubiquitylation of FBW7 occurs preferentially on K404 and K412, but is not sufficient for its proteasomal degradation, and in addition requires TRIP12-mediated branched K11-linked ubiquitylation. TRIP12 inactivation causes FBW7 protein accumulation and increased proteasomal degradation of the SCFFBW7 substrate Myeloid Leukemia 1 (MCL1), and sensitizes cancer cells to anti-tubulin chemotherapy. Concomitant FBW7 inactivation rescues the effects of TRIP12 deficiency, confirming FBW7 as an essential mediator of TRIP12 function. This work reveals an unexpected complexity of FBW7 ubiquitylation, and highlights branched ubiquitylation as an important signalling mechanism regulating protein stability.
Dominant role of CDKN2B/p15INK4B of 9p21.3 tumor suppressor hub in inhibition of cell-cycle and glycolysis
Authors: Xia Yong , Liu Yan , Yang Chao , Simeone Diane M. , Sun Tung-Tien , DeGraff David J. , Tang Moon-shong , Zhang Yingkai , Wu Xue-Ru 
Published: April 2021

AbstractHuman chromosome 9p21.3 is susceptible to inactivation in cell immortalization and diseases, such as cancer, coronary artery disease and type-2 diabetes. Although this locus encodes three cyclin-dependent kinase (CDK) inhibitors (p15INK4B, p14ARF and p16INK4A), our understanding of their functions and modes of action is limited to the latter two. Here, we show that in vitro p15INK4B is markedly stronger than p16INK4A in inhibiting pRb1 phosphorylation, E2F activity and cell-cycle progression. In mice, urothelial cells expressing oncogenic HRas and lacking p15INK4B, but not those expressing HRas and lacking p16INK4A, develop early-onset bladder tumors. The potency of CDKN2B/p15INK4B in tumor suppression relies on its strong binding via key N-terminal residues to and inhibition of CDK4/CDK6. p15INK4B also binds and inhibits enolase-1, a glycolytic enzyme upregulated in most cancer types. Our results highlight the dual inhibition of p15INK4B on cell proliferation, and unveil mechanisms whereby p15INK4B aberrations may underpin cancer and non-cancer conditions.
Giant c-axis nonlinear anomalous Hall effect in Td-MoTe2 and WTe2
Authors: Tiwari Archana , Chen Fangchu , Zhong Shazhou , Drueke Elizabeth , Koo Jahyun , Kaczmarek Austin , Xiao Cong , Gao Jingjing , Luo Xuan , Niu Qian , Sun Yuping , Yan Binghai , Zhao Liuyan , Tsen Adam W. 
Published: April 2021

AbstractWhile the anomalous Hall effect can manifest even without an external magnetic field, time reversal symmetry is nonetheless still broken by the internal magnetization of the sample. Recently, it has been shown that certain materials without an inversion center allow for a nonlinear type of anomalous Hall effect whilst retaining time reversal symmetry. The effect may arise from either Berry curvature or through various asymmetric scattering mechanisms. Here, we report the observation of an extremely large c-axis nonlinear anomalous Hall effect in the non-centrosymmetric Td phase of MoTe2 and WTe2 without intrinsic magnetic order. We find that the effect is dominated by skew-scattering at higher temperatures combined with another scattering process active at low temperatures. Application of higher bias yields an extremely large Hall ratio of E⊥/E|| = 2.47 and corresponding anomalous Hall conductivity of order 8 × 107 S/m.
A policy roadmap for negative emissions using direct air capture
Authors: Meckling Jonas , Biber Eric 
Published: April 2021

AbstractNegative emission strategies are central to avoiding catastrophic climate change. Engineered solutions such as direct air capture are far from cost-competitive. As past low-carbon technology transitions suggest, this calls for policy and political strategies beyond carbon pricing. We adopt a policy sequencing perspective that identifies policies that could create niche markets, building political support for later widespread deployment of direct air capture. Climate leaders could pursue an “incentives + mandates” policy strategy targeted at the oil and gas industry. These early moves could create global spillovers for follower countries by reducing technology cost and facilitating knowledge transfer through global firms.
Discovery of $${\hat{\boldsymbol{C}}}_2$$ rotation anomaly in topological crystalline insulator SrPb
Authors: Fan Wenhui , Nie Simin , Wang Cuixiang , Fu Binbin , Yi Changjiang , Gao Shunye , Rao Zhicheng , Yan Dayu , Ma Junzhang , Shi Ming , Huang Yaobo , Shi Youguo , Wang Zhijun , Qian Tian , Ding Hong 
Published: April 2021

AbstractTopological crystalline insulators (TCIs) are insulating electronic states with nontrivial topology protected by crystalline symmetries. Recently, theory has proposed new classes of TCIs protected by rotation symmetries$$\hat C_n$$Ĉn, which have surface rotation anomaly evading the fermion doubling theorem, i.e.,ninstead of 2nDirac cones on the surface preserving the rotation symmetry. Here, we report the first realization of the$$\hat C_2$$Ĉ2rotation anomaly in a binary compound SrPb. Our first-principles calculations reveal two massless Dirac fermions protected by the combination of time-reversal symmetry$$\hat T$$T̂and$$\hat C_{2y}$$Ĉ2yon the (010) surface. Using angle-resolved photoemission spectroscopy, we identify two Dirac surface states inside the bulk band gap of SrPb, confirming the$$\hat C_2$$Ĉ2rotation anomaly in the new classes of TCIs. The findings enrich the classification of topological phases, which pave the way for exploring exotic behavior of the new classes of TCIs.
Biochemical and structural characterization of the BioZ enzyme engaged in bacterial biotin synthesis pathway
Authors: Zhang Sitao , Xu Yongchang , Guan Hongxin , Cui Tao , Liao Yuling , Wei Wenhui , Li Jun , Hassan Bachar H. , Zhang Huimin , Jia Xu , Ouyang Songying , Feng Youjun 
Published: April 2021

AbstractBiotin is an essential micro-nutrient across the three domains of life. The paradigm earlier step of biotin synthesis denotes “BioC-BioH” pathway inEscherichia coli. Here we report that BioZ bypasses the canonical route to begin biotin synthesis. In addition to its origin ofRhizobiales, protein phylogeny infers that BioZ is domesticated to gain an atypical role of β-ketoacyl-ACP synthase III. Genetic and biochemical characterization demonstrates that BioZ catalyzes the condensation of glutaryl-CoA (or ACP) with malonyl-ACP to give 5’-keto-pimeloyl ACP. This intermediate proceeds via type II fatty acid synthesis (FAS II) pathway, to initiate the formation of pimeloyl-ACP, a precursor of biotin synthesis. To further explore molecular basis of BioZ activity, we determine the crystal structure ofAgrobacterium tumefaciensBioZ at 1.99 Å, of which the catalytic triad and the substrate-loading tunnel are functionally defined. In particular, we localize that three residues (S84, R147, and S287) at the distant bottom of the tunnel might neutralize the charge of free C-carboxyl group of the primer glutaryl-CoA. Taken together, this study provides molecular insights into the BioZ biotin synthesis pathway.
Coordinated interactions between endothelial cells and macrophages in the islet microenvironment promote β cell regeneration
Authors: Saunders Diane C. , Aamodt Kristie I. , Richardson Tiffany M. , Hopkirk Alexander J. , Aramandla Radhika , Poffenberger Greg , Jenkins Regina , Flaherty David K. , Prasad Nripesh , Levy Shawn E. , Powers Alvin C. , Brissova Marcela 
Published: April 2021

AbstractEndogenous β cell regeneration could alleviate diabetes, but proliferative stimuli within the islet microenvironment are incompletely understood. We previously found that β cell recovery following hypervascularization-induced β cell loss involves interactions with endothelial cells (ECs) and macrophages (MΦs). Here we show that proliferative ECs modulate MΦ infiltration and phenotype during β cell loss, and recruited MΦs are essential for β cell recovery. Furthermore, VEGFR2 inactivation in quiescent ECs accelerates islet vascular regression during β cell recovery and leads to increased β cell proliferation without changes in MΦ phenotype or number. Transcriptome analysis of β cells, ECs, and MΦs reveals that β cell proliferation coincides with elevated expression of extracellular matrix remodeling molecules and growth factors likely driving activation of proliferative signaling pathways in β cells. Collectively, these findings suggest a new β cell regeneration paradigm whereby coordinated interactions between intra-islet MΦs, ECs, and extracellular matrix mediate β cell self-renewal.
Catalyst-loaded micro-encapsulated phase change material for thermal control of exothermic reaction
Authors: Takahashi Tatsuya , Koide Hiroaki , Sakai Hiroki , Ajito Daisuke , Kurniawan Ade , Kunisada Yuji , Nomura Takahiro 
Published: April 2021

AbstractCO2 methanation is a promising technology to enable the use of CO2 as a resource. Thermal control of CO2 methanation, which is a highly active exothermic reaction, is important to avoid thermal runaway and subsequent degradation of the catalyst. Using the heat storage capacity of a phase change material (PCM) for thermal control of the reaction is a novel passive approach. In this study a novel structure was developed, wherein catalysts were directly loaded onto a micro-encapsulated PCM (MEPCM). The MEPCM was prepared in three steps consisting of a boehmite treatment, precipitation treatment, and heat oxidation treatment, and an impregnation process was adopted to prepare a Ni catalyst. The catalyst-loaded MEPCM did not show any breakage or deformation of the capsule or a decrease in the heat storage capacity after the impregnation treatment. MEPCM demonstrated a higher potential as an alternative catalyst support in CO2 methanation than the commercially available α-Al2O3 particle. In addition, the heat storage capacity of the catalyst-loaded MEPCM suppressed the temperature rise of the catalyst bed at a high heat absorption rate (2.5 MW m−3). In conclusion, the catalyst-loaded MEPCM is a high-speed, high-precision thermal control device because of its high-density energy storage and resolution of a spatial gap between the catalyst and cooling devices. This novel concept has the potential to overcome the technical challenges faced by efficiency enhancement of industrial chemical reactions.
The effect of dietary supplementation with Nigella sativa (black seeds) mediates immunological function in male Wistar rats
Authors: Mahmoud Hany Salah , Almallah Amani A. , Gad EL-Hak Heba Nageh , Aldayel Tahany Saleh , Abdelrazek Heba M. A. , Khaled Howayda E. 
Published: April 2021

AbstractThis experiment aimed to investigate the effect of dietary Nigella sativa on the cell-mediated immune response. Eighteen male Wistar rats were divided equally into a control group and treated groups that received black seeds at rates of 30 and 50 g/kg in the diet (Sa30 and Sa50 groups, respectively, for 30 days. The weight gain, feed intake, feed conversion ratio (FCR), and cell-mediated immune response were monitored after the injection of 0.1 mL of 10% phytohemagglutinin (PHA). The intumesce index, serum total antioxidant capacity (TAC), catalase (CAT), interleukin-12 (IL-12), gamma interferon (γ-IF) and tumor necrosis factor alpha (TNF-α) were determined. Histopathological examination and an immunohistochemistry analysis of splenic caspase-3 and CD8 were performed.Nigella sativa significantly improved the weight gain and FCR. Intumesce index of Sa50 group was significantly increased.Nigella sativasignificantly increased TAC, CAT, IL-12, γ-IF and TNF-α. A histological examination of PHA-stimulated foot pads showed increased leukocyte infiltration and edema in a dose-dependent pattern. Splenic caspase-3 and CD8 showed significant decreases and increases, respectively, in the Sa30 and Sa50 groups. The results indicate thatNigella sativaseeds exhibit immunostimulatory function through their antioxidant potential, induction of cytokine production, promotion of CD8 expression and reduction of splenic apoptosis.
Improves symptoms and urinary biomarkers in refractory interstitial cystitis/bladder pain syndrome patients randomized to extracorporeal shock wave therapy versus placebo
Authors: Shen Yuan-Chi , Tyagi Pradeep , Lee Wei-Chia , Chancellor Michael , Chuang Yao-Chi 
Published: April 2021

AbstractExtracorporeal shock wave therapy (ESWT) has been shown to improve symptoms in patients with interstitial cystitis/bladder pain syndrome (IC/BPS); however, there is a lack of objective evidence. We measured change of urinary biomarker levels in 25 patients with IC/BPS received ESWT or placebo once a week for 4 weeks. Urines were collected from participants at baseline, 4 and 12 weeks post treatment. A representative 41 inflammatory growth factors, cytokines, and chemokines in urine were measured using a MILLIPLEX immunoassay kit. Symptom bother was assessed by O’Leary-Sant symptom scores (OSS), and visual analog scale (VAS) for pain. The ESWT group exhibited a significant reduction in the OSS and VAS compared to the placebo group 4 weeks post-treatment (P < 0.05), and the effects were persistent at 12 weeks. The difference in urinary markers change in ESWT versus placebo was P = 0.054 for IL4, P = 0.013 for VEGF, and P = 0.039 for IL9 at 4 weeks. The change of urine biomarker was not significant in other biomarkers or all the measured proteins at 12 weeks. The current data suggest that IL4, IL9, and VEGF mediation may be involved in its pathophysiologic mechanisms and response to LESW treatment.
White matter abnormalities in adults with bipolar disorder type-II and unipolar depression
Authors: Manelis Anna , Soehner Adriane , Halchenko Yaroslav O. , Satz Skye , Ragozzino Rachel , Lucero Mora , Swartz Holly A. , Phillips Mary L. , Versace Amelia 
Published: April 2021

AbstractDiscerning distinct neurobiological characteristics of related mood disorders such as bipolar disorder type-II (BD-II) and unipolar depression (UD) is challenging due to overlapping symptoms and patterns of disruption in brain regions. More than 60% of individuals with UD experience subthreshold hypomanic symptoms such as elevated mood, irritability, and increased activity. Previous studies linked bipolar disorder to widespread white matter abnormalities. However, no published work has compared white matter microstructure in individuals with BD-II vs. UD vs. healthy controls (HC), or examined the relationship between spectrum (dimensional) measures of hypomania and white matter microstructure across those individuals. This study aimed to examine fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and mean diffusivity (MD) across BD-II, UD, and HC groups in the white matter tracts identified by the XTRACT tool in FSL. Individuals with BD-II (n = 18), UD (n = 23), and HC (n = 24) underwent Diffusion Weighted Imaging. The categorical approach revealed decreased FA and increased RD in BD-II and UD vs. HC across multiple tracts. While BD-II had significantly lower FA and higher RD values than UD in the anterior part of the left arcuate fasciculus, UD had significantly lower FA and higher RD values than BD-II in the area of intersections between the right arcuate, inferior fronto-occipital and uncinate fasciculi and forceps minor. The dimensional approach revealed the depression-by-spectrum mania interaction effect on the FA, RD, and AD values in the area of intersection between the right posterior arcuate and middle longitudinal fasciculi. We propose that the white matter microstructure in these tracts reflects a unique pathophysiologic signature and compensatory mechanisms distinguishing BD-II from UD.
Plasma microrna expression profile for reduced ejection fraction in dilated cardiomyopathy
Authors: Calderon-Dominguez Maria , Belmonte Thalía , Quezada-Feijoo Maribel , Ramos Mónica , Calderon-Dominguez Juan , Campuzano Oscar , Mangas Alipio , Toro Rocio 
Published: April 2021

AbstractThe left ventricular (LV) ejection fraction (EF) is key to prognosis in dilated cardiomyopathy (DCM). Circulating microRNAs have emerged as reliable biomarkers for heart diseases, included DCM. Clinicians need improved tools for greater clarification of DCM EF categorization, to identify high-risk patients. Thus, we investigated whether microRNA profiles can categorize DCM patients based on their EF. 179-differentially expressed circulating microRNAs were screened in two groups: (1) non-idiopathic DCM; (2) idiopathic DCM. Then, 26 microRNAs were identified and validated in the plasma of ischemic-DCM (n = 60), idiopathic-DCM (n = 55) and healthy individuals (n = 44). We identified fourteen microRNAs associated with echocardiographic variables that differentiated idiopathic DCM according to the EF degree. A predictive model of a three-microRNA (miR-130b-3p, miR-150-5p and miR-210-3p) combined with clinical variables (left bundle branch block, left ventricle end-systolic dimension, lower systolic blood pressure and smoking habit) was obtained for idiopathic DCM with a severely reduced-EF. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. Bioinformatics analysis revealed that miR-150-5p and miR-210-3p target genes might interact with each other with a high connectivity degree. In conclusion, our results revealed a three-microRNA signature combined with clinical variables that highly discriminate idiopathic DCM categorization. This is a potential novel prognostic biomarker with high clinical value.
Intelligent long-term performance analysis in power electronics systems
Authors: Peyghami Saeed , Dragicevic Tomislav , Blaabjerg Frede 
Published: April 2021

AbstractThis paper proposes a long-term performance indicator for power electronic converters based on their reliability. The converter reliability is represented by the proposed constant lifetime curves, which have been developed using Artificial Neural Network (ANN) under different operating conditions. Unlike the state-of-the-art theoretical reliability modeling approaches, which employ detailed electro-thermal characteristics and lifetime models of converter components, the proposed method provides a nonparametric surrogate model of the converter based on limited non-linear data from theoretical reliability analysis. The proposed approach can quickly predict the converter lifetime under given operating conditions without a further need for extended, time-consuming electro-thermal analysis. Moreover, the proposed lifetime curves can present the long-term performance of converters facilitating optimal system-level design for reliability, reliable operation and maintenance planning in power electronic systems. Numerical case studies evaluate the effectiveness of the proposed reliability modeling approach.