bluuebunny/crossref_metadata_2025_split huggingface dataset:
Photoactivatable CaMKII induces synaptic plasticity in single synapses
Authors: Shibata Akihiro C. E. , Ueda Hiromi H. , Eto Kei , Onda Maki , Sato Aiko , Ohba Tatsuko , Nabekura Junichi , Murakoshi Hideji 
Published: February 2021

AbstractOptogenetic approaches for studying neuronal functions have proven their utility in the neurosciences. However, optogenetic tools capable of inducing synaptic plasticity at the level of single synapses have been lacking. Here, we engineered a photoactivatable (pa)CaMKII by fusing a light-sensitive domain, LOV2, to CaMKIIα. Blue light or two-photon excitation reversibly activated paCaMKII. Activation in single spines was sufficient to induce structural long-term potentiation (sLTP) in vitro and in vivo. paCaMKII activation was also sufficient for the recruitment of AMPA receptors and functional LTP in single spines. By combining paCaMKII with protein activity imaging by 2-photon FLIM-FRET, we demonstrate that paCaMKII activation in clustered spines induces robust sLTP via a mechanism that involves the actin-regulatory small GTPase, Cdc42. This optogenetic tool for dissecting the function of CaMKII activation (i.e., the sufficiency of CaMKII rather than necessity) and for manipulating synaptic plasticity will find many applications in neuroscience and other fields.
Structural basis for ligand recognition of the neuropeptide Y Y2 receptor
Authors: Tang Tingting , Hartig Christin , Chen Qiuru , Zhao Wenli , Kaiser Anette , Zhang Xuefeng , Zhang Hui , Qu Honge , Yi Cuiying , Ma Limin , Han Shuo , Zhao Qiang , Beck-Sickinger Annette G. , Wu Beili 
Published: February 2021

AbstractThe human neuropeptide Y (NPY) Y2 receptor (Y2R) plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y2R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y2R bound to a selective antagonist JNJ-31020028 at 2.8 Å resolution. The structure reveals molecular details of the ligand-binding mode of Y2R. Combined with mutagenesis studies, the Y2R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y1R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design.
Tumour heterogeneity and intercellular networks of nasopharyngeal carcinoma at single cell resolution
Authors: Liu Yang , He Shuai , Wang Xi-Liang , Peng Wan , Chen Qiu-Yan , Chi Dong-Mei , Chen Jie-Rong , Han Bo-Wei , Lin Guo-Wang , Li Yi-Qi , Wang Qian-Yu , Peng Rou-Jun , Wei Pan-Pan , Guo Xiang , Li Bo , Xia Xiaojun , Mai Hai-Qiang , Hu Xue-Da , Zhang Zemin , Zeng Yi-Xin , Bei Jin-Xin 
Published: February 2021

AbstractThe heterogeneous nature of tumour microenvironment (TME) underlying diverse treatment responses remains unclear in nasopharyngeal carcinoma (NPC). Here, we profile 176,447 cells from 10 NPC tumour-blood pairs, using single-cell transcriptome coupled with T cell receptor sequencing. Our analyses reveal 53 cell subtypes, including tumour-infiltrating CD8+T, regulatory T (Treg), and dendritic cells (DCs), as well as malignant cells with different Epstein-Barr virus infection status. Trajectory analyses reveal exhausted CD8+T and immune-suppressive TNFRSF4+Treg cells in tumours might derive from peripheral CX3CR1+CD8+T and naïve Treg cells, respectively. Moreover, we identify immune-regulatory and tolerogenic LAMP3+DCs. Noteworthily, we observe intensive inter-cell interactions among LAMP3+DCs, Treg, exhausted CD8+T, and malignant cells, suggesting potential cross-talks to foster an immune-suppressive niche for the TME. Collectively, our study uncovers the heterogeneity and interacting molecules of the TME in NPC at single-cell resolution, which provide insights into the mechanisms underlying NPC progression and the development of precise therapies for NPC.
Structure of papain-like protease from SARS-CoV-2 and its complexes with non-covalent inhibitors
Authors: Osipiuk Jerzy , Azizi Saara-Anne , Dvorkin Steve , Endres Michael , Jedrzejczak Robert , Jones Krysten A. , Kang Soowon , Kathayat Rahul S. , Kim Youngchang , Lisnyak Vladislav G. , Maki Samantha L. , Nicolaescu Vlad , Taylor Cooper A. , Tesar Christine , Zhang Yu-An , Zhou Zhiyao , Randall Glenn , Michalska Karolina , Snyder Scott A. , Dickinson Bryan C. , Joachimiak Andrzej 
Published: February 2021

AbstractThe pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) continues to expand. Papain-like protease (PLpro) is one of two SARS-CoV-2 proteases potentially targetable with antivirals. PLpro is an attractive target because it plays an essential role in cleavage and maturation of viral polyproteins, assembly of the replicase-transcriptase complex, and disruption of host responses. We report a substantive body of structural, biochemical, and virus replication studies that identify several inhibitors of the SARS-CoV-2 enzyme. We determined the high resolution structure of wild-type PLpro, the active site C111S mutant, and their complexes with inhibitors. This collection of structures details inhibitors recognition and interactions providing fundamental molecular and mechanistic insight into PLpro. All compounds inhibit the peptidase activity of PLpro in vitro, some block SARS-CoV-2 replication in cell culture assays. These findings will accelerate structure-based drug design efforts targeting PLpro to identify high-affinity inhibitors of clinical value.
Impaired visual working memory and reduced connectivity in undergraduates with a history of mild traumatic brain injury
Authors: Arciniega Hector , Shires Jorja , Furlong Sarah , Kilgore-Gomez Alexandrea , Cerreta Adelle , Murray Nicholas G. , Berryhill Marian E. 
Published: February 2021

AbstractMild traumatic brain injury (mTBI), or concussion, accounts for 85% of all TBIs. Yet survivors anticipate full cognitive recovery within several months of injury, if not sooner, dependent upon the specific outcome/measure. Recovery is variable and deficits in executive function, e.g., working memory (WM) can persist years post-mTBI. We tested whether cognitive deficits persist in otherwise healthy undergraduates, as a conservative indicator for mTBI survivors at large. We collected WM performance (change detection, n-back tasks) using various stimuli (shapes, locations, letters; aurally presented numbers and letters), and wide-ranging cognitive assessments (e.g., RBANS). We replicated the observation of a general visual WM deficit, with preserved auditory WM. Surprisingly, visual WM deficits were equivalent in participants with a history of mTBI (mean 4.3 years post-injury) and in undergraduates with recent sports-related mTBI (mean 17 days post-injury). In seeking the underlying mechanism of these behavioral deficits, we collected resting state fMRI (rsfMRI) and EEG (rsEEG). RsfMRI revealed significantly reduced connectivity within WM-relevant networks (default mode, central executive, dorsal attention, salience), whereas rsEEG identified no differences (modularity, global efficiency, local efficiency). In summary, otherwise healthy current undergraduates with a history of mTBI present behavioral deficits with evidence of persistent disconnection long after full recovery is expected.
Computational 4D-OCM for label-free imaging of collective cell invasion and force-mediated deformations in collagen
Authors: Mulligan Jeffrey A. , Ling Lu , Leartprapun Nichaluk , Fischbach Claudia , Adie Steven G. 
Published: February 2021

AbstractTraction force microscopy (TFM) is an important family of techniques used to measure and study the role of cellular traction forces (CTFs) associated with many biological processes. However, current standard TFM methods rely on imaging techniques that do not provide the experimental capabilities necessary to study CTFs within 3D collective and dynamic systems embedded within optically scattering media. Traction force optical coherence microscopy (TF-OCM) was developed to address these needs, but has only been demonstrated for the study of isolated cells embedded within optically clear media. Here, we present computational 4D-OCM methods that enable the study of dynamic invasion behavior of large tumor spheroids embedded in collagen. Our multi-day, time-lapse imaging data provided detailed visualizations of evolving spheroid morphology, collagen degradation, and collagen deformation, all using label-free scattering contrast. These capabilities, which provided insights into how stromal cells affect cancer progression, significantly expand access to critical data about biophysical interactions of cells with their environment, and lay the foundation for future efforts toward volumetric, time-lapse reconstructions of collective CTFs with TF-OCM.
Inner and outer retinal layer thickness alterations in pediatric and juvenile craniopharyngioma
Authors: Lee Ga-In , Park Kyung-Ah , Oh Sei Yeul , Kong Doo-Sik , Hong Sang Duk 
Published: February 2021

AbstractWe evaluated postoperative retinal thickness in pediatric and juvenile craniopharyngioma (CP) patients with chiasmal compression using optical coherence tomography (OCT) auto-segmentation. We included 18 eyes of 18 pediatric or juvenile patients with CP and 20 healthy controls. Each thickness of the macular retinal nerve fiber layer (RNFL), ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer, outer plexiform layer, outer nuclear layer, and photoreceptor layer was compared between the CP patients and healthy controls. There was significant thinning in the macular RNFL (estimates [μm], superior, − 10.68; inferior, − 7.24; nasal, − 14.22), all quadrants of GCL (superior, − 16.53; inferior, − 14.37; nasal, − 24.34; temporal, − 9.91) and IPL (superior, − 11.45; inferior, − 9.76; nasal, − 15.25; temporal, − 4.97) in pediatric and juvenile CP patients postoperatively compared to healthy control eyes after adjusting for age and refractive errors. Thickness reduction in the average and nasal quadrant of RNFL, GCL, and IPL was associated with peripapillary RNFL thickness, and reduced nasal quadrant GCL and IPL thicknesses were associated with postoperative visual field defects. In pediatric and juvenile patients with CP, decreased inner retinal layer thickness following chiasmal compression was observed. The changes in retinal structures were closely related to peripapillary RNFL thinning and functional outcomes.
Imaging of photoacoustic-mediated permeabilization of giant unilamellar vesicles (GUVs)
Authors: Pereira Diogo A. , Silva Alexandre D. , Martins Patricia A. T. , Piedade Ana P. , Martynowych Dmitro , Veysset David , Moreno Maria João , Serpa Carlos , Nelson Keith A. , Arnaut Luis G. 
Published: February 2021

AbstractTarget delivery of large foreign materials to cells requires transient permeabilization of the cell membrane without toxicity. Giant unilamellar vesicles (GUVs) mimic the phospholipid bilayer of the cell membrane and are also useful drug delivery vehicles. Controlled increase of the permeability of GUVs is a delicate balance between sufficient perturbation for the delivery of the GUV contents and damage to the vesicles. Here we show that photoacoustic waves can promote the release of FITC-dextran or GFP from GUVs without damage. Real-time interferometric imaging offers the first movies of photoacoustic wave propagation and interaction with GUVs. The photoacoustic waves are seen as mostly compressive half-cycle pulses with peak pressures of ~ 1 MPa and spatial extent FWHM ~ 36 µm. At a repetition rate of 10 Hz, they enable the release of 25% of the FITC-dextran content of GUVs in 15 min. Such photoacoustic waves may enable non-invasive targeted release of GUVs and cell transfection over large volumes of tissues in just a few minutes.
Elevated hemoglobin is independently associated with enlarged perivascular spaces in the central semiovale
Authors: Huo Yingchao , Huang Siyuan , Li Rui , Gong Xue , Zhang Wenyu , Zhang Rongrong , Qin Xinyue 
Published: February 2021

AbstractEnlarged perivascular spaces (EPVS) are widely considered as a feature of cerebral small vessel diseases (SVD), but its underlying pathology is still under active investigation. The aim of this study was to explore the association between hemoglobin level and the severity of EPVS. Consecutive patients with acute ischemic stroke who underwent baseline MRI scan and hemoglobin testing were evaluated. EPVS in basal ganglia (BG) and central semiovale (CS) were rated with a validated 4-point semiquantitative scale (0 = none; 1 = 1–10; 2 = 11–20; 3 = 21–40; and 4 ≥ 40). Bivariate logistic regression models were used to identify the associations of hemoglobin with predefined high-degree (score > 1) CS-EPVS and BG-EPVS. Multinomial logistic regression models were used to analyze the associations between hemoglobin and CS-/BG-EPVS predominance patterns. A total of 401 patients were included in the final analysis, 94 patients (23.4%) had a high degree of CS-EPVS and 45 patients (11.2%) had a high degree of BG-EPVS. Compared with tertile 1 of hemoglobin, tertile 3 of hemoglobin was independently associated with high degree of CS-EPVS after adjusting for other features of SVD (odds ratio [OR] 2.399, 95% confidence interval [CI] 1.315–4.379, P = 0.004) and potential confounding factors (OR 2.611, 95% CI 1.346–5.066, P = 0.005). In multinomial logistic regression models, compared with tertile 1 of hemoglobin, tertile 2 (OR 2.463, 95% CI 1.195–5.075, P = 0.015) and tertile 3 (OR 2.625, 95% CI 1.102–6.251, P = 0.029) of hemoglobin were associated with higher odds of BG-EPVS = CS-EPVS pattern, and tertile 3 of hemoglobin (OR 2.576, 95% CI 1.004–6.608, P = 0.049) was associated with higher odds of BG-EPVS < CS-EPVS pattern. Elevated hemoglobin level was independently associated with high degree of CS-EPVS and higher odds of CS-EPVS predominance pattern, but not with BG-EPVS, which support that the topography of EPVS is characteristic. However, the pathogenesis linking hemoglobin and CS-EPVS is unclear and still needs further investigation.
Correlation between serum carbohydrate antigen 19-9 levels and computed tomography severity score in patients with nontuberculous mycobacterial pulmonary disease
Authors: Kim Kangjoon , Yong Seung Hyun , Lee Su Hwan , Lee Sang Hoon , Leem Ah Young , Kim Song Yee , Chung Kyungsoo , Kim Eun Young , Jung Ji Ye , Park Moo Suk , Kim Young Sam , Lee Hye-Jeong , Kang Young Ae 
Published: February 2021

AbstractThere is no validated clinical biomarker for disease severity or treatment response for nontuberculous mycobacterial pulmonary disease (NTM-PD). We investigated the correlation between elevated serum carbohydrate antigen (CA) 19-9 levels and NTM-PD disease activity, defined using an imaging severity score based on chest computed tomography (CT). We retrospectively examined 79 patients with NTM-PD who underwent serum CA19-9 level assessments and chest CT less than 1 month apart. NTM-PD severity was rated using a CT-based scoring system. The correlation between the CT score and serum CA19-9 levels was evaluated. Chest CT revealed nodular bronchiectasis without cavitation in most patients (78.5%). Serum CA19-9 levels were elevated in 19 (24%) patients. Serum CA19-9 levels were positively correlated with the total CT score and bronchiectasis, bronchiolitis, cavity, and consolidation subscores. Partial correlation analysis revealed a significant positive correlation between serum CA19-9 levels and CT scores for total score and bronchiectasis, bronchiolitis, cavitation, and consolidation subscores after controlling for age, sex, and BMI. Serum CA19-9 levels were positively correlated with the CT severity score for NTM-PD. Serum CA19-9 may be useful in evaluating disease activity or therapeutic response in patients with NTM-PD.
In a model of SAH-induced neurogenic fever, BAT thermogenesis is mediated by erythrocytes and blocked by agonism of adenosine A1 receptors
Authors: Tupone Domenico , Cetas Justin S. 
Published: February 2021

AbstractNeurogenic fever (NF) after subarachnoid hemorrhage (SAH) is a major cause of morbidity that is associated with poor outcomes and prolonged stay in the neurointensive care unit (NICU). Though SAH is a much more common cause of fever than sepsis in the NICU, it is often a diagnosis of exclusion, requiring significant effort to rule out an infectious source. NF does not respond to standard anti-pyretic medications such as COX inhibitors, and lack of good medical therapy has led to the introduction of external cooling systems that have their own associated problems. In a rodent model of SAH, we measured the effects of injecting whole blood, blood plasma, or erythrocytes on the sympathetic nerve activity to brown adipose tissue and on febrile thermogenesis. We demonstrate that following SAH the acute activation of brown adipose tissue leading to NF, is not dependent on PGE2, that subarachnoid space injection of whole blood or erythrocytes, but not plasma alone, is sufficient to trigger brown adipose tissue thermogenesis, and that activation of adenosine A1 receptors in the CNS can block the brown adipose tissue thermogenic component contributing to NF after SAH. These findings point to a distinct thermogenic mechanism for generating NF, compared to those due to infectious causes, and will hopefully lead to new therapies.
Time course of the sensitivity and specificity of anti-SARS-CoV-2 IgM and IgG antibodies for symptomatic COVID-19 in Japan
Authors: Nakano Yuki , Kurano Makoto , Morita Yoshifumi , Shimura Takuya , Yokoyama Rin , Qian Chungen , Xia Fuzhen , He Fan , Kishi Yoshiro , Okada Jun , Yoshikawa Naoyuki , Nagura Yutaka , Okazaki Hitoshi , Moriya Kyoji , Seto Yasuyuki , Kodama Tatsuhiko , Yatomi Yutaka 
Published: February 2021

AbstractThe accurate and prompt diagnosis of SARS-CoV-2 infection is required for the control and treatment of the coronavirus infection disease 2019 (COVID-19). In this study, we aimed to investigate the time courses of the anti-severe acute corona respiratory syndrome coronavirus 2 (SARS-CoV-2) IgM and IgG titers and to evaluate the sensitivity and specificity of such tests according to the specific day after the onset of COVID-19 among a patient population in Japan. We measured the titers of SARS-CoV-2 IgM and IgG in sera from 105 subjects, including 26 symptomatic COVID-19 patients, using chemiluminescent immunoassay (CLIA) methods utilizing magnetic beads coated with SARS-CoV-2 nucleocapsid protein and spike protein. The results of a ROC analysis suggested the possibility that the cutoff values in Japan might be lower than the manufacturer’s reported cutoff (10 AU/mL): 1 AU/mL for IgM and 5 AU/mL for IgG. The sensitivity of the test before Day 8 after symptom onset was less than 50%; at Days 9–10, however, we obtained a much higher sensitivity of 81.8% for both IgM and IgG. At 15 days or later after symptom onset, the SARS-CoV-2 IgG test had a sensitivity of 100%. These results suggest that if the number of days since disease onset is taken into consideration, these antibody tests could be very useful for the diagnosis of COVID-19 and similar diseases.
Volatile 1-octanol of tea (Camellia sinensis L.) fuels cell division and indole-3-acetic acid production in phylloplane isolate Pseudomonas sp. NEEL19
Authors: Neelakandan Poovarasan , Young Chiu-Chung , Hameed Asif , Wang Yu-Ning , Chen Kui-Nuo , Shen Fo-Ting 
Published: February 2021

AbstractTea leaves possess numerous volatile organic compounds (VOC) that contribute to tea’s characteristic aroma. Some components of tea VOC were known to exhibit antimicrobial activity; however, their impact on bacteria remains elusive. Here, we showed that the VOC of fresh aqueous tea leaf extract, recovered through hydrodistillation, promoted cell division and tryptophan-dependent indole-3-acetic acid (IAA) production in Pseudomonas sp. NEEL19, a solvent-tolerant isolate of the tea phylloplane. 1-octanol was identified as one of the responsible volatiles stimulating cell division, metabolic change, swimming motility, putative pili/nanowire formation and IAA production, through gas chromatography-mass spectrometry, microscopy and partition petri dish culture analyses. The bacterial metabolic responses including IAA production increased under 1-octanol vapor in a dose-dependent manner, whereas direct-contact in liquid culture failed to elicit such response. Thus, volatile 1-octanol emitting from tea leaves is a potential modulator of cell division, colonization and phytohormone production in NEEL19, possibly influencing the tea aroma.
Implications of monsoon season and UVB radiation for COVID-19 in India
Authors: Moozhipurath Rahul Kalippurayil , Kraft Lennart 
Published: February 2021

AbstractIndia has recorded 142,186 deaths over 36 administrative regions placing India third in the world after the US and Brazil for COVID-19 deaths as of 12 December 2020. Studies indicate that south-west monsoon season plays a role in the dynamics of contagious diseases, which tend to peak post-monsoon season. Recent studies show that vitamin D and its primary source Ultraviolet-B (UVB) radiation may play a protective role in mitigating COVID-19 deaths. However, the combined roles of the monsoon season and UVB radiation in COVID-19 in India remain still unclear. In this observational study, we empirically study the respective roles of monsoon season and UVB radiation, whilst further exploring, whether the monsoon season negatively impacts the protective role of UVB radiation in COVID-19 deaths in India. We use a log-linear Mundlak model to a panel dataset of 36 administrative regions in India from 14 March 2020–19 November 2020 (n = 6751). We use the cumulative COVID-19 deaths as the dependent variable. We isolate the association of monsoon season and UVB radiation as measured by Ultraviolet Index (UVI) from other confounding time-constant and time-varying region-specific factors. After controlling for various confounding factors, we observe that a unit increase in UVI and the monsoon season are separately associated with 1.2 percentage points and 7.5 percentage points decline in growth rates of COVID-19 deaths in the long run. These associations translate into substantial relative changes. For example, a permanent unit increase of UVI is associated with a decrease of growth rates of COVID-19 deaths by 33% (= − 1.2 percentage points) However, the monsoon season, mitigates the protective role of UVI by 77% (0.92 percentage points). Our results indicate a protective role of UVB radiation in mitigating COVID-19 deaths in India. Furthermore, we find evidence that the monsoon season is associated with a significant reduction in the protective role of UVB radiation. Our study outlines the roles of the monsoon season and UVB radiation in COVID-19 in India and supports health-related policy decision making in India.