bluuebunny/crossref_metadata_2025_split huggingface dataset:
S-adenosylmethionine upregulates the angiotensin receptor-binding protein ATRAP via the methylation of HuR in NAFLD
Authors: Guo Tao , Dai Zhe , You Ke , Battaglia-Hsu Shyue-Fang , Feng Juan , Wang Fengliang , Li Bao , Yang Jian , Li Zhen 
Published: March 2021

AbstractNonalcoholic fatty liver disease (NAFLD) has emerged globally and is associated with inflammatory signaling. The underlying mechanisms remain poorly delineated, although NAFLD has attracted considerable attention and been extensively investigated. Recent publications have determined that angiotensin II (Ang II) plays an important role in stimulating NAFLD progression by causing lipid metabolism disorder and insulin resistance through its main receptor, Ang II type 1 receptor (AT1R). Herein, we explored the effect of supplementary S-adenosylmethionine (SAM), which is the main biological methyl donor in mammalian cells, in regulating AT1R-associated protein (ATRAP), which is the negative regulator of AT1R. We found that SAM was depleted in NAFLD and that SAM supplementation ameliorated steatosis. In addition, in both high-fat diet-fed C57BL/6 rats and L02 cells treated with oleic acid (OA), ATRAP expression was downregulated at lower SAM concentrations. Mechanistically, we found that the subcellular localization of human antigen R (HuR) was determined by the SAM concentration due to protein methylation modification. Moreover, HuR was demonstrated to directly bind ATRAP mRNA and control its nucleocytoplasmic shuttling. Thus, SAM was suggested to upregulate ATRAP protein expression by maintaining the export of its mRNA from the nucleus. Taken together, our findings suggest that SAM can positively regulate ATRAP in NAFLD and may have various potential benefits for the treatment of NAFLD.
The adipokine Retnla deficiency increases responsiveness to cardiac repair through adiponectin-rich bone marrow cells
Authors: Kim Yong Sook , Cho Hyang Hee , Cho Dong Im , Jeong Hye-yun , Lim Soo yeon , Jun Ju Hee , Kim Mi Ra , Kang Bo Gyeong , Cho Meeyoung , Kang Hye-jin , Kang Wan Seok , Oh Goo Taeg , Ahn Youngkeun 
Published: March 2021

AbstractResistin-like alpha (Retnla) is a member of the resistin family and known to modulate fibrosis and inflammation. Here, we investigated the role of Retnla in the cardiac injury model. Myocardial infarction (MI) was induced in wild type (WT), Retnla knockout (KO), and Retnla transgenic (TG) mice. Cardiac function was assessed by echocardiography and was significantly preserved in the KO mice, while worsened in the TG group. Angiogenesis was substantially increased in the KO mice, and cardiomyocyte apoptosis was markedly suppressed in the KO mice. By Retnla treatment, the expression of p21 and the ratio of Bax to Bcl2 were increased in cardiomyocytes, while decreased in cardiac fibroblasts. Interestingly, the numbers of cardiac macrophages and unsorted bone marrow cells (UBCs) were higher in the KO mice than in the WT mice. Besides, phosphorylated histone H3(+) cells were more frequent in bone marrow of KO mice. Moreover, adiponectin in UBCs was notably higher in the KO mice compared with WT mice. In an adoptive transfer study, UBCs were isolated from KO mice to transplant to the WT infarcted heart. Cardiac function was better in the KO-UBCs transplanted group in the WT-UBCs transplanted group. Taken together, proliferative and adiponectin-rich bone marrow niche was associated with substantial cardiac recovery by suppression of cardiac apoptosis and proliferation of cardiac fibroblast.
Enhanced CNS transduction from AAV.PHP.eB infusion into the cisterna magna of older adult rats compared to AAV9
Authors: Chatterjee Diptaman , Marmion David J. , McBride Jodi L. , Manfredsson Fredric P. , Butler David , Messer Anne , Kordower Jeffrey H. 
Published: March 2021

AbstractThe development of high efficiency, central nervous system (CNS) targeting AAV-based gene therapies is necessary to address challenges in both pre-clinical and clinical investigations. The engineered capsids, AAV.PHP.B and AAV.PHP.eB, show vastly improved blood-brain barrier penetration compared to their parent serotype, AAV9, but with variable effect depending on animal system, strain, and delivery route. As most characterizations of AAV.PHP variants have been performed in mice, it is currently unknown whether AAV.PHP variants improve CNS targeting when delivered intrathecally in rats. We evaluated the comparative transduction efficiencies of equititer doses (6 × 1011vg) of AAV.PHP.eB-CAG-GFP and AAV9-CAG-GFP when delivered into the cisterna magna of 6–9-month old rats. Using both quantitative and qualitative assessments, we observed consistently superior biodistribution of GFP+ cells and fibers in animals treated with AAV.PHP.eB compared to those treated with AAV9. Enhanced GFP signal was uniformly observed throughout rostrocaudal brain regions in AAV.PHP.eB-treated animals with matching GFP protein expression detected in the forebrain, midbrain, and cerebellum. Collectively, these data illustrate the benefit of intracisternal infusions of AAV.PHP.eB as an optimal system to distribute CNS gene therapies in preclinical investigations of rats, and may have important translational implications for the clinical CNS targeting.
Reconstructing unseen transmission events to infer dengue dynamics from viral sequences
Authors: Salje Henrik , Wesolowski Amy , Brown Tyler S. , Kiang Mathew V. , Berry Irina Maljkovic , Lefrancq Noemie , Fernandez Stefan , Jarman Richard G. , Ruchusatsawat Kriangsak , Iamsirithaworn Sopon , Vandepitte Warunee P. , Suntarattiwong Piyarat , Read Jonathan M. , Klungthong Chonticha , Thaisomboonsuk Butsaya , Engø-Monsen Kenth , Buckee Caroline , Cauchemez Simon , Cummings Derek A. T. 
Published: March 2021

AbstractFor most pathogens, transmission is driven by interactions between the behaviours of infectious individuals, the behaviours of the wider population, the local environment, and immunity. Phylogeographic approaches are currently unable to disentangle the relative effects of these competing factors. We develop a spatiotemporally structured phylogenetic framework that addresses these limitations by considering individual transmission events, reconstructed across spatial scales. We apply it to geocoded dengue virus sequences from Thailand (N = 726 over 18 years). We find infected individuals spend 96% of their time in their home community compared to 76% for the susceptible population (mainly children) and 42% for adults. Dynamic pockets of local immunity make transmission more likely in places with high heterotypic immunity and less likely where high homotypic immunity exists. Age-dependent mixing of individuals and vector distributions are not important in determining spread. This approach provides previously unknown insights into one of the most complex disease systems known and will be applicable to other pathogens.
Multispectral camouflage for infrared, visible, lasers and microwave with radiative cooling
Authors: Zhu Huanzheng , Li Qiang , Tao Chenning , Hong Yu , Xu Ziquan , Shen Weidong , Kaur Sandeep , Ghosh Pintu , Qiu Min 
Published: March 2021

AbstractInterminable surveillance and reconnaissance through various sophisticated multispectral detectors present threats to military equipment and manpower. However, a combination of detectors operating in different wavelength bands (from hundreds of nanometers to centimeters) and based on different principles raises challenges to the conventional single-band camouflage devices. In this paper, multispectral camouflage is demonstrated for the visible, mid-infrared (MIR, 3–5 and 8–14 μm), lasers (1.55 and 10.6 μm) and microwave (8–12 GHz) bands with simultaneous efficient radiative cooling in the non-atmospheric window (5–8 μm). The device for multispectral camouflage consists of a ZnS/Ge multilayer for wavelength selective emission and a Cu-ITO-Cu metasurface for microwave absorption. In comparison with conventional broadband low emittance material (Cr), the IR camouflage performance of this device manifests 8.4/5.9 °C reduction of inner/surface temperature, and 53.4/13.0% IR signal decrease in mid/long wavelength IR bands, at 2500 W ∙ m−2input power density. Furthermore, we reveal that the natural convection in the atmosphere can be enhanced by radiation in the non-atmospheric window, which increases the total cooling power from 136 W ∙ m−2to 252 W ∙ m−2at 150 °C surface temperature. This work may introduce the opportunities for multispectral manipulation, infrared signal processing, thermal management, and energy-efficient applications.
A modular tool to query and inducibly disrupt biomolecular condensates
Authors: Hernández-Candia Carmen N. , Pearce Sarah , Tucker Chandra L. 
Published: March 2021

AbstractDynamic membraneless compartments formed by protein condensates have multifunctional roles in cellular biology. Tools that inducibly trigger condensate formation have been useful for exploring their cellular function, however, there are few tools that provide inducible control over condensate disruption. To address this need we developed DisCo (Disassembly of Condensates), which relies on the use of chemical dimerizers to inducibly recruit a ligand to the condensate-forming protein, triggering condensate dissociation. We demonstrate use of DisCo to disrupt condensates of FUS, associated with amyotrophic lateral sclerosis, and to prevent formation of polyglutamine-containing huntingtin condensates, associated with Huntington’s disease. In addition, we combined DisCo with a tool to induce condensates with light, CRY2olig, achieving bidirectional control of condensate formation and disassembly using orthogonal inputs of light and rapamycin. Our results demonstrate a method to manipulate condensate states that will have broad utility, enabling better understanding of the biological role of condensates in health and disease.
A homogeneous split-luciferase assay for rapid and sensitive detection of anti-SARS CoV-2 antibodies
Authors: Yao Zhong , Drecun Luka , Aboualizadeh Farzaneh , Kim Sun Jin , Li Zhijie , Wood Heidi , Valcourt Emelissa J. , Manguiat Kathy , Plenderleith Simon , Yip Lily , Li Xinliu , Zhong Zoe , Yue Feng Yun , Closas Tatiana , Snider Jamie , Tomic Jelena , Drews Steven J. , Drebot Michael A. , McGeer Allison , Ostrowski Mario , Mubareka Samira , Rini James M. , Owen Shawn , Stagljar Igor 
Published: March 2021

AbstractBetter diagnostic tools are needed to combat the ongoing COVID-19 pandemic. Here, to meet this urgent demand, we report a homogeneous immunoassay to detect IgG antibodies against SARS-CoV-2. This serological assay, called SATiN, is based on a tri-part Nanoluciferase (tNLuc) approach, in which the spike protein of SARS-CoV-2 and protein G, fused respectively to two different tNLuc tags, are used as antibody probes. Target engagement of the probes allows reconstitution of a functional luciferase in the presence of the third tNLuc component. The assay is performed directly in the liquid phase of patient sera and enables rapid, quantitative and low-cost detection. We show that SATiN has a similar sensitivity to ELISA, and its readouts are consistent with various neutralizing antibody assays. This proof-of-principle study suggests potential applications in diagnostics, as well as disease and vaccination management.
Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy
Authors: Weinhofer Isabelle , Rommer Paulus , Zierfuss Bettina , Altmann Patrick , Foiani Martha , Heslegrave Amanda , Zetterberg Henrik , Gleiss Andreas , Musolino Patricia L. , Gong Yi , Forss-Petter Sonja , Berger Thomas , Eichler Florian , Aubourg Patrick , Köhler Wolfgang , Berger Johannes 
Published: March 2021

AbstractX-linked adrenoleukodystrophy (X-ALD), the most frequent monogenetic disorder of brain white matter, is highly variable, ranging from slowly progressive adrenomyeloneuropathy (AMN) to life-threatening inflammatory brain demyelination (CALD). In this study involving 94 X-ALD patients and 55 controls, we tested whether plasma/serum neurofilament light chain protein (NfL) constitutes an early distinguishing biomarker. In AMN, we found moderately elevated NfL with increased levels reflecting higher grading of myelopathy-related disability. Intriguingly, NfL was a significant predictor to discriminate non-converting AMN from cohorts later developing CALD. In CALD, markedly amplified NfL levels reflected brain lesion severity. In rare cases, atypically low NfL revealed a previously unrecognized smoldering CALD disease course with slowly progressive myelin destruction. Upon halt of brain demyelination by hematopoietic stem cell transplantation, NfL gradually normalized. Together, our study reveals that blood NfL reflects inflammatory activity and progression in CALD patients, thus constituting a potential surrogate biomarker that may facilitate clinical decisions and therapeutic development.
The origins and genetic interactions of KRAS mutations are allele- and tissue-specific
Authors: Cook Joshua H. , Melloni Giorgio E. M. , Gulhan Doga C. , Park Peter J. , Haigis Kevin M. 
Published: March 2021

AbstractMutational activation of KRAS promotes the initiation and progression of cancers, especially in the colorectum, pancreas, lung, and blood plasma, with varying prevalence of specific activating missense mutations. Although epidemiological studies connect specific alleles to clinical outcomes, the mechanisms underlying the distinct clinical characteristics of mutant KRAS alleles are unclear. Here, we analyze 13,492 samples from these four tumor types to examine allele- and tissue-specific genetic properties associated with oncogenic KRAS mutations. The prevalence of known mutagenic mechanisms partially explains the observed spectrum of KRAS activating mutations. However, there are substantial differences between the observed and predicted frequencies for many alleles, suggesting that biological selection underlies the tissue-specific frequencies of mutant alleles. Consistent with experimental studies that have identified distinct signaling properties associated with each mutant form of KRAS, our genetic analysis reveals that each KRAS allele is associated with a distinct tissue-specific comutation network. Moreover, we identify tissue-specific genetic dependencies associated with specific mutant KRAS alleles. Overall, this analysis demonstrates that the genetic interactions of oncogenic KRAS mutations are allele- and tissue-specific, underscoring the complexity that drives their clinical consequences.
Isotopic evidence for the formation of the Moon in a canonical giant impact
Authors: Nielsen Sune G. , Bekaert David V. , Auro Maureen 
Published: March 2021

AbstractIsotopic measurements of lunar and terrestrial rocks have revealed that, unlike any other body in the solar system, the Moon is indistinguishable from the Earth for nearly every isotopic system. This observation, however, contradicts predictions by the standard model for the origin of the Moon, the canonical giant impact. Here we show that the vanadium isotopic composition of the Moon is offset from that of the bulk silicate Earth by 0.18 ± 0.04 parts per thousand towards the chondritic value. This offset most likely results from isotope fractionation on proto-Earth during the main stage of terrestrial core formation (pre-giant impact), followed by a canonical giant impact where ~80% of the Moon originates from the impactor of chondritic composition. Our data refute the possibility of post-giant impact equilibration between the Earth and Moon, and implies that the impactor and proto-Earth mainly accreted from a common isotopic reservoir in the inner solar system.
Development of an X-Band Reflectarray Antenna for Satellite Communications
Authors: Ma Bing , Lu Fan , Zhi Guoping , Xue Xin , Zhao Xiangni , Ma Chao , Fan Yong , Yang Mei 
Published: March 2021

AbstractAn X-band reflectarray antenna using 16 × 12 double square ring elements for satellite communications is proposed in this paper. The feed is a 4 × 3 elements microstrip patch array designed to create edge taper of approximately − 10 dB. A prototype with right-hand circular polarization (RHCP) is manufactured and tested, and the good agreements between simulations and measurements are demonstrated. The good performance is obtained with the aperture efficiency of 40.7% and the 3-dB gain bandwidth of about 10% which is beneficial to nanosatellites.
Morphodynamic signatures of MDA-MB-231 single cells and cell doublets undergoing invasion in confined microenvironments
Authors: Zhang Xingjian , Chan Trevor , Mak Michael 
Published: March 2021

AbstractCancer cell metastasis is a major factor in cancer-related mortality. During the process of metastasis, cancer cells exhibit migratory phenotypes and invade through pores in the dense extracellular matrix. However, the characterization of morphological and subcellular features of cells in similar migratory phenotypes and the effects of geometric confinement on cell morphodynamics are not well understood. Here, we investigate the phenotypes of highly aggressive MDA-MB-231 cells in single cell and cell doublet (an initial and simplified collective state) forms in confined microenvironments. We group phenotypically similar single cells and cell doublets and characterize related morphological and subcellular features. We further detect two distinct migratory phenotypes, fluctuating and non-fluctuating, within the fast migrating single cell group. In addition, we demonstrate an increase in the number of protrusions formed at the leading edge of cells after invasion through geometric confinement. Finally, we track the short and long term effects of varied degrees of confinement on protrusion formation. Overall, our findings elucidate the underlying morphological and subcellular features associated with different single cell and cell doublet phenotypes and the impact of invasion through confined geometry on cell behavior.
The relationship between cardiac injury, inflammation and coagulation in predicting COVID-19 outcome
Authors: Mengozzi Alessandro , Georgiopoulos Georgios , Falcone Marco , Tiseo Giusy , Pugliese Nicola Riccardo , Dimopoulos Meletios A. , Ghiadoni Lorenzo , Barbieri Greta , Forfori Francesco , Carrozzi Laura , Santini Massimo , Monzani Fabio , De Marco Salvatore , Menichetti Francesco , Virdis Agostino , Masi Stefano ,   Pisa Covid Study Group, Sabrina Agostini o Degl’Innocenti , Martina Biancalana , Matteo Borselli , Elia Nencini , Stefano Spinelli , Rachele Antognoli , Valeria Calsolario , Simone Paterni , Rubia Baldassarri , Pietro Bertini , Giulia Brizzi , Francesco Corradi , Alessandra Della Rocca , Fabio Guarracino , Paolo Malacarne , Marco Monfroni , Chiara Piagnani , Alessandro Celi , Francesco Cinotti , Naria Park , Alessandro Cipriano , Luciano Colangelo , Chiara Sonato , Valentina Galfo , Uliana Monica , Francesca Ruberti , Giovanna Forotti , Maria Sciuto 
Published: March 2021

AbstractHigh sensitivity troponin T (hsTnT) is a strong predictor of adverse outcome during SARS-CoV-2 infection. However, its determinants remain partially unknown. We aimed to assess the relationship between severity of inflammatory response/coagulation abnormalities and hsTnT in Coronavirus Disease 2019 (COVID-19). We then explored the relevance of these pathways in defining mortality and complications risk and the potential effects of the treatments to attenuate such risk. In this single-center, prospective, observational study we enrolled 266 consecutive patients hospitalized for SARS-CoV-2 pneumonia. Primary endpoint was in-hospital COVID-19 mortality. hsTnT, even after adjustment for confounders, was associated with mortality. D-dimer and CRP presented stronger associations with hsTnT than PaO2. Changes of hsTnT, D-dimer and CRP were related; but only D-dimer was associated with mortality. Moreover, low molecular weight heparin showed attenuation of the mortality in the whole population, particularly in subjects with higher hsTnT. D-dimer possessed a strong relationship with hsTnT and mortality. Anticoagulation treatment showed greater benefits with regard to mortality. These findings suggest a major role of SARS-CoV-2 coagulopathy in hsTnT elevation and its related mortality in COVID-19. A better understanding of the mechanisms related to COVID-19 might pave the way to therapy tailoring in these high-risk individuals.
Islet sympathetic innervation and islet neuropathology in patients with type 1 diabetes
Authors: Campbell-Thompson Martha , Butterworth Elizabeth A. , Boatwright J. Lucas , Nair Malavika A. , Nasif Lith H. , Nasif Kamal , Revell Andy Y. , Riva Alberto , Mathews Clayton E. , Gerling Ivan C. , Schatz Desmond A. , Atkinson Mark A. 
Published: March 2021

AbstractDysregulation of glucagon secretion in type 1 diabetes (T1D) involves hypersecretion during postprandial states, but insufficient secretion during hypoglycemia. The sympathetic nervous system regulates glucagon secretion. To investigate islet sympathetic innervation in T1D, sympathetic tyrosine hydroxylase (TH) axons were analyzed in control non-diabetic organ donors, non-diabetic islet autoantibody-positive individuals (AAb), and age-matched persons with T1D. Islet TH axon numbers and density were significantly decreased in AAb compared to T1D with no significant differences observed in exocrine TH axon volume or lengths between groups. TH axons were in close approximation to islet α-cells in T1D individuals with long-standing diabetes. Islet RNA-sequencing and qRT-PCR analyses identified significant alterations in noradrenalin degradation, α-adrenergic signaling, cardiac β-adrenergic signaling, catecholamine biosynthesis, and additional neuropathology pathways. The close approximation of TH axons at islet α-cells supports a model for sympathetic efferent neurons directly regulating glucagon secretion. Sympathetic islet innervation and intrinsic adrenergic signaling pathways could be novel targets for improving glucagon secretion in T1D.
The effect of training intensity on implicit learning rates in schizophrenia
Authors: Orlov Natasza D. , Sanderson Jessica , Muqtadir Syed Ali , Kalpakidou Anastasia K. , Michalopoulou Panayiota G. , Lu Jie , Shergill Sukhi S. 
Published: March 2021

AbstractCognitive impairments in learning and memory are core symptoms of schizophrenia, associated with reduced self-reported quality of life. The most effective treatment of cognitive impairments is drill and practice cognitive training. Still, to date no study has investigated the effect of varying the frequency of training on cognitive outcomes. Here we utilized a verbal memory based language learning task, tapping into implicit cognitive processes, to investigate the role of training intensity on learning rates in individuals with schizophrenia. Data from 47 participants across two studies was utilized, one with a daily training regimen over 5 days and the other with a more intensive schedule of 5 sessions delivered over 2 days. The primary outcome measure was the change in implicit learning performance across five sessions, quantified with the Matthews Correlation Coefficient (MCC). Participants in the daily training group showed improved performance compared to the intensive group only at session 4. This is the first study to show that implicit learning rates are influenced by training intensity, with daily sessions outperforming a more intensive regimen; a period of consolidation overnight may be necessary to optimize cognitive training for individuals with schizophrenia.