bluuebunny/crossref_metadata_2025_split huggingface dataset:
Early life experiences selectively mature learning and memory abilities
Authors: Bessières Benjamin , Travaglia Alessio , Mowery Todd M. , Zhang Xinying , Alberini Cristina M. 
Published: January 2020

AbstractThe mechanisms underlying the maturation of learning and memory abilities are poorly understood. Here we show that episodic learning produces unique biological changes in the hippocampus of infant rats and mice compared to juveniles and adults. These changes include persistent neuronal activation, BDNF-dependent increase in the excitatory synapse markers synaptophysin and PSD-95, and significant maturation of AMPA receptor synaptic responses. Inhibition of PSD-95 induction following learning impairs both AMPA receptor response maturation and infantile memory, indicating that the synapse formation/maturation is necessary for creating infantile memories. Conversely, capturing the learning-induced changes by presenting a subsequent learning experience or by chemogenetic activation of the neural ensembles tagged by learning matures memory functional competence. This memory competence is selective for the type of experience encountered, as it transfers within similar hippocampus-dependent learning domains but not to other hippocampus-dependent types of learning. Thus, experiences in early life produce selective maturation of memory abilities.
Structural insights into selective interaction between type IIa receptor protein tyrosine phosphatases and Liprin-α
Authors: Wakita Maiko , Yamagata Atsushi , Shiroshima Tomoko , Izumi Hironori , Maeda Asami , Sendo Mizuki , Imai Ayako , Kubota Keiko , Goto-Ito Sakurako , Sato Yusuke , Mori Hisashi , Yoshida Tomoyuki , Fukai Shuya 
Published: January 2020

AbstractSynapse formation is induced by transsynaptic interaction of neuronal cell-adhesion molecules termed synaptic organizers. Type IIa receptor protein tyrosine phosphatases (IIa RPTPs) function as presynaptic organizers. The cytoplasmic domain of IIa RPTPs consists of two phosphatase domains, and the membrane-distal one (D2) is essential for synapse formation. Liprin-α, which is an active zone protein critical for synapse formation, interacts with D2 via its C-terminal domain composed of three tandem sterile alpha motifs (tSAM). Structural mechanisms of this critical interaction for synapse formation remain elusive. Here, we report the crystal structure of the complex between mouse PTPδ D2 and Liprin-α3 tSAM at 1.91 Å resolution. PTPδ D2 interacts with the N-terminal helix and the first and second SAMs (SAM1 and SAM2, respectively) of Liprin-α3. Structure-based mutational analyses in vitro and in cellulo demonstrate that the interactions with Liprin-α SAM1 and SAM2 are essential for the binding and synaptogenic activity.
Synthesis of ppGpp impacts type IX secretion and biofilm matrix formation in Porphyromonas gingivalis
Authors: Kim Hey-Min , Davey Mary E. 
Published: January 2020

AbstractIn order to persist, bacteria need to adjust their physiological state in response to external and internal cues. External stimuli are often referred to as stressors. The stringent response, mediated by the alarmone (p)ppGpp, is central to the stress response in many bacteria; yet, there is limited knowledge regarding the role of (p)ppGpp signaling in bacteria belonging to the phylum Bacteroidetes. Like its counterparts in the gut (e.g., Bacteroides thetaiotaomicron and Bacteroides fragilis), Porphyromonas gingivalis persists in close association with its human host. Given the potential for numerous perturbations in the oral cavity, and the fact that P. gingivalis can enter and replicate within host cells, we hypothesized that (p)ppGpp is a key signaling molecule for stress adaptation and persistence. Here, we show that accumulation of ppGpp in P. gingivalis is governed by two homologous enzymes, designated Rel, and RshB, and that ppGpp signaling affects growth rate, survival, biofilm formation, production of outer membrane vesicles, and expression of genes encoding type IX secretion structural and cargo proteins. Overall, our findings provide a potential mechanism by which biofilm formation and virulence of P. gingivalis are integrated via ppGpp signaling, a regulatory mechanism central to bacterial survival in dynamic environments.
Quantifying Reoxygenation in Pancreatic Cancer During Stereotactic Body Radiotherapy
Authors: Taylor Edward , Zhou Jitao , Lindsay Patricia , Foltz Warren , Cheung May , Siddiqui Iram , Hosni Ali , Amir Ahmed El , Kim John , Hill Richard P. , Jaffray David A. , Hedley David W. 
Published: January 2020

AbstractHypoxia, the state of low oxygenation that often arises in solid tumours due to their high metabolism and irregular vasculature, is a major contributor to the resistance of tumours to radiation therapy (RT) and other treatments. Conventional RT extends treatment over several weeks or more, and nominally allows time for oxygen levels to increase (“reoxygenation”) as cancer cells are killed by RT, mitigating the impact of hypoxia. Recent advances in RT have led to an increase in the use stereotactic body radiotherapy (SBRT), which delivers high doses in five or fewer fractions. For cancers such as pancreatic adenocarcinoma for which hypoxia varies significantly between patients, SBRT might not be optimal, depending on the extent to which reoxygenation occurs during its short duration. We used fluoro-5-deoxy-α-D-arabinofuranosyl)-2-nitroimidazole positron-emission tomography (FAZA-PET) imaging to quantify hypoxia before and after 5-fraction SBRT delivered to patient-derived pancreatic cancer xenografts orthotopically implanted in mice. An imaging technique using only the pre-treatment FAZA-PET scan and repeat dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) scans throughout treatment was able to predict the change in hypoxia. Our results support the further testing of this technique for imaging of reoxygenation in the clinic.
Multi-platform NMR Study of Pluripotent Stem Cells Unveils Complementary Metabolic Signatures towards Differentiation
Authors: Elena-Herrmann Bénédicte , Montellier Emilie , Fages Anne , Bruck-Haimson Reut , Moussaieff Arieh 
Published: January 2020

AbstractStem cells, poised to revolutionize current medicine, stand as major workhorses for monitoring changes in cell fate. Characterizing metabolic phenotypes is key to monitor in differentiating cells transcriptional and epigenetic shifts at a functional level and provides a non-genetic means to control cell specification. Expanding the arsenal of analytical tools for metabolic profiling of cell differentiation is therefore of importance. Here, we describe the metabolome of whole pluripotent stem cells (PSCs) using high‐resolution magic angle spinning (HR-MAS), a non-destructive approach for Nuclear Magnetic Resonance (NMR) analysis. The integrated 1H NMR analysis results in detection of metabolites of various groups, including energy metabolites, amino acids, choline derivatives and short chain fatty acids. It unveils new metabolites that discriminate PSCs from differentiated counterparts and directly measures substrates and co-factors of histone modifying enzymes, suggesting that NMR stands as a strategic technique for deciphering metabolic regulations of histone post-translational modifications. HR-MAS NMR analysis of whole PSCs complements the much used solution NMR of cell extracts. Altogether, our multi-platform NMR investigation provides a consolidated picture of PSC metabolic signatures and of metabolic pathways involved in differentiation.
Safety and efficacy of stereotactic radiofrequency ablation for very large (≥8 cm) primary and metastatic liver tumors
Authors: Schullian Peter , Johnston Edward W. , Putzer Daniel , Eberle Gernot , Laimer Gregor , Bale Reto 
Published: January 2020

AbstractTo assess the safety and clinical outcomes of multi-probe stereotactic radiofrequency ablation (SRFA) for very large (≥8 cm) primary and metastatic liver tumors with curative treatment intent. A retrospective, single center study carried out between 01.2005 and 06.2018. 34 consecutive patients had a total of 41 primary and metastatic liver tumors with a median size of 9.0 cm (8.0–18.0 cm) at initial SRFA. Patients were treated under CT guidance using a 3D navigation system. Endpoints consisted of (i) technical efficacy; primary - requiring one treatment, and secondary – requiring two treatments (ii) complication and mortality rates (iii) local and distant recurrence (LR), (iv) disease free survival (DFS), (v) overall survival (OS). 33/41 tumors were successfully ablated at initial SRFA (80.5% primary technical efficacy rate (PTE)). Four tumors required repeat ablation, resulting in a secondary technical efficacy (STE) rate of 90.2%. Local tumor recurrence (LR) developed in 4 of 41 tumors (9.8%). The 30-day perioperative mortality was 2.3% (1/ 44 ablations). The total major complication rate was 20.5% (9 of 44 ablations). Three of nine (33.3%) major complications, such as pleural effusion, pneumothoraces or perihepatic hemorrhages were relatively easy to treat. The overall survival (OS) rates at 1-, 3-, and 5- years from the date of the first SRFA were 87.1%, 71.8%, and 62.8% for patients with hepatocellular carcinoma (HCC) and 87.5%, 70.0% and 70.0% for patients with intrahepatic cholangiocarcinoma (ICC) respectively. Patients with metastatic disease had OS rates of 77.8% and 22.2% at 1- and 3- years. The clinical results of SRFA in this study are encouraging and warrant a prospective multicenter study. SRFA may become one of the best therapeutic choices for a growing number of patients with primary and metastatic liver cancer.
Socioeconomic prospects of a seaweed bioeconomy in Sweden
Authors: Hasselström Linus , Thomas Jean-Baptiste , Nordström Jonas , Cervin Gunnar , Nylund Göran M. , Pavia Henrik , Gröndahl Fredrik 
Published: January 2020

AbstractSeaweed cultivation is a large industry worldwide, but production in Europe is small compared to production in Asian countries. In the EU, the motivations for seaweed farming may be seen from two perspectives; one being economic growth through biomass production and the other being the provisioning of ecosystem services such as mitigating eutrophication. In this paper, we assess the economic potential of large-scale cultivation of kelp, Saccharina latissima, along the Swedish west coast, including the value of externalities. The findings suggest that seaweed farming has the potential of becoming a profitable industry in Sweden. Furthermore, large-scale seaweed farming can sequester a significant share of annual anthropogenic nitrogen and phosphorus inflows to the basins of the Swedish west coast (8% of N and 60% of P). Concerning the valuation of externalities, positive values generated from sequestration of nitrogen and phosphorus are potentially counteracted by negative values from interference with recreational values. Despite the large N and P uptake, the socioeconomic value of this sequestration is only a minor share of the potential financial value from biomass production. This suggests that e.g. payment schemes for nutrient uptake based on the socioeconomic values generated is not likely to be a tipping point for the industry. Additionally, seaweed cultivation is not a cost-efficient measure in itself to remove nutrients. Policy should thus be oriented towards industry development, as the market potential of the biomass will be the driver that may unlock these bioremediation opportunities.
Nox2 dependent redox-regulation of microglial response to amyloid-β stimulation and microgliosis in aging
Authors: Geng Li , Fan Lampson M. , Liu Fangfei , Smith Colin , Li Jian -Mei 
Published: January 2020

AbstractMicroglia express constitutively a Nox2 enzyme that is involved in neuroinflammation by the generation of reactive oxygen species (ROS). Amyloid β (Aβ) plays a crucial role in Alzheimer’s disease. However, the mechanism of Aβ-induced microglial dysfunction and redox-regulation of microgliosis in aging remains unclear. In this study, we examined Nox2-derived ROS in mediating microglial response to Aβ peptide 1–42 (Aβ42) stimulation in vitro, in aging-associated microgliosis in vivo and in post-mortem human samples. Compared to controls, Aβ42 markedly induced BV2 cell ROS production, Nox2 expression, p47phox and ERK1/2 phosphorylation, cell proliferation and IL-1β secretion. All these changes could be inhibited to the control levels in the presence of Nox2 inhibitor or superoxide scavenger. Compared to young (3–4 months) controls, midbrain tissues from wild-type aging mice (20–22 months) had significantly higher levels of Nox2-derived ROS production, Aβ deposition, microgliosis and IL-1β production. However, these aging-related changes were reduced or absent in Nox2 knockout aging mice. Clinical significance of aging-associated Nox2 activation, microgliosis and IL-1β production was investigated using post-mortem midbrain tissues of humans at young (25–38 years) and old age (61–85 years). In conclusion, Nox2-dependent redox-signalling is crucial in microglial response to Aβ42 stimulation and in aging-associated microgliosis and brain inflammation.
Synergistic effects of repair, resilience and retention of damage determine the conditions for replicative ageing
Authors: Borgqvist Johannes , Welkenhuysen Niek , Cvijovic Marija 
Published: January 2020

AbstractAccumulation of damaged proteins is a hallmark of ageing, occurring in organisms ranging from bacteria and yeast to mammalian cells. During cell division in Saccharomyces cerevisiae, damaged proteins are retained within the mother cell, resulting in an ageing mother while a new daughter cell exhibits full replicative potential. The cell-specific features determining the ageing remain elusive. It has been suggested that the replicative ageing is dependent on the ability of the cell to repair and retain pre-existing damage. To deepen the understanding of how these factors influence the life of individual cells, we developed and experimentally validated a dynamic model of damage accumulation accounting for replicative ageing on the single cell level. The model includes five essential properties: cell growth, damage formation, damage repair, cell division and cell death, represented in a theoretical framework describing the conditions allowing for replicative ageing, starvation, immortality or clonal senescence. We introduce the resilience to damage, which can be interpreted as the difference in volume between an old and a young cell. We show that the capacity to retain damage deteriorates with high age, that asymmetric division allows for retention of damage, and that there is a trade-off between retention and the resilience property. Finally, we derive the maximal degree of asymmetry as a function of resilience, proposing that asymmetric cell division is beneficial with respect to replicative ageing as it increases the lifespan of a given organism. The proposed model contributes to a deeper understanding of the ageing process in eukaryotic organisms.
The Quantitative-Phase Dynamics of Apoptosis and Lytic Cell Death
Authors: Vicar Tomas , Raudenska Martina , Gumulec Jaromir , Balvan Jan 
Published: January 2020

AbstractCell viability and cytotoxicity assays are highly important for drug screening and cytotoxicity tests of antineoplastic or other therapeutic drugs. Even though biochemical-based tests are very helpful to obtain preliminary preview, their results should be confirmed by methods based on direct cell death assessment. In this study, time-dependent changes in quantitative phase-based parameters during cell death were determined and methodology useable for rapid and label-free assessment of direct cell death was introduced. The goal of our study was distinction between apoptosis and primary lytic cell death based on morphologic features. We have distinguished the lytic and non-lytic type of cell death according to their end-point features (Dance of Death typical for apoptosis versus swelling and membrane rupture typical for all kinds of necrosis common for necroptosis, pyroptosis, ferroptosis and accidental cell death). Our method utilizes Quantitative Phase Imaging (QPI) which enables the time-lapse observation of subtle changes in cell mass distribution. According to our results, morphological and dynamical features extracted from QPI micrographs are suitable for cell death detection (76% accuracy in comparison with manual annotation). Furthermore, based on QPI data alone and machine learning, we were able to classify typical dynamical changes of cell morphology during both caspase 3,7-dependent and -independent cell death subroutines. The main parameters used for label-free detection of these cell death modalities were cell density (pg/pixel) and average intensity change of cell pixels further designated as Cell Dynamic Score (CDS). To the best of our knowledge, this is the first study introducing CDS and cell density as a parameter typical for individual cell death subroutines with prediction accuracy 75.4% for caspase 3,7-dependent and -independent cell death.
“Diabetic striatopathy”: clinical presentations, controversy, pathogenesis, treatments, and outcomes
Authors: Chua Choon-Bing , Sun Cheuk-Kwan , Hsu Chih-Wei , Tai Yi-Cheng , Liang Chih-Yu , Tsai I-Ting 
Published: January 2020

AbstractDiabetic striatopathy (DS) is a rare medical condition with ambiguous nomenclature. We searched PubMed database from 1992 to 2018 for articles describing hyperglycemia associated with chorea/ballism and/or neuroimages of striatal abnormalities. Descriptive analysis was performed on demographic/clinical characteristics, locations of striatal abnormalities on neuroimages, pathology findings, treatment strategies, and outcomes. In total, 176 patients (male:female = 1:1.7) were identified from 72 articles with mean age 67.6 ± 15.9 (range, 8–92). Among them, 96.6% had type 2 DM with 17% being newly diagnosed. Average blood glucose and glycated hemoglobin concentrations were 414 mg/dL and 13.1%, respectively. Most patients (88.1%) presented with hemichorea/hemiballism. Isolated putamen and combined putamen-caudate nucleus involvements were most common on neuroimaging studies with discrepancies between CT and MRI findings in about one-sixth of patients. Unilateral arm-leg combination was the most frequent with bilateral chorea in 9.7% of patients. Chorea and imaging anomalies did not appear concomitantly in one-tenth of patients. Successful treatment rates of chorea with glucose-control-only and additional anti-chorea medications were 25.7% and 76.2%, respectively, with an overall recurrence rate being 18.2%. The most commonly used anti-chorea drug was haloperidol. To date, four out of six pathological studies revealed evidence of hemorrhage as a probable pathogenesis.
Structural basis for Glycan-receptor binding by mumps virus hemagglutinin-neuraminidase
Authors: Forgione Rosa Ester , Di Carluccio Cristina , Kubota Marie , Manabe Yoshiyuki , Fukase Koichi , Molinaro Antonio , Hashiguchi Takao , Marchetti Roberta , Silipo Alba 
Published: January 2020

AbstractMumps virus is one of the main cause of respiratory illnesses in humans, especially children. Among the viral surface glycoproteins, the hemagglutinin – neuraminidase, MuV-HN, plays key roles in virus entry into host cells and infectivity, thus representing an ideal target for the design of novel inhibitors. Here we report the detailed analysis of the molecular recognition of host cell surface sialylated glycans by the viral glycoprotein MuV-HN. By a combined use of NMR, docking, molecular modelling and CORCEMA-ST, the structural features of sialoglycans/MuV-HN complexes were revealed. Evidence for a different enzyme activity toward longer and complex substrates compared to unbranched ligands was also examined by an accurate NMR kinetic analysis. Our results provide the basis for the structure-based design of effective drugs against mumps-induced diseases.
Quzhou Fructus Aurantii Extract suppresses inflammation via regulation of MAPK, NF-κB, and AMPK signaling pathway
Authors: Li Lili , Chen Jiaoting , Lin Lin , Pan Guixuan , Zhang Sheng , Chen Hao , Zhang Majuan , Xuan Yaoxian , Wang Yin , You Zhenqiang 
Published: January 2020

AbstractThe anti-inflammatory activity of Quzhou Fructus Aurantii Extract (QFAE) has been reported recently. Thus, present study aims to explore the mechanism of anti-inflammation of QFAE in vitro and in vivo to develop a lung phylactic agent. The anti-inflammatory mechanism of QFAE in RAW 264.7 cells and acute lung injury (ALI) mice model was determined by cytokines analysis, histopathological examination, Western blot assay, immunofluorescence, and immunohistochemistry analysis. The results showed that QFAE restrained mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways in LPS-induced RAW 264.7 cells, whereas AMP-activated protein kinase (AMPK) signaling pathways were activated, as revealed by prominent attenuation of phosphorylation of ERK, JNK, p38, p65, IκBα, RSK and MSK, and overt enhancement of phosphorylation of ACC and AMPKα. The levels of pro-inflammatory cytokines TNF, IL-6, and IL-1β were suppressed, whereas the level of anti-inflammatory cytokine IL-10 increased after pretreatment with QFAE in vivo and in vitro. Moreover, QFAE prevented mice from LPS-provoked ALI, bases on alleviating neutrophils, and macrophages in bronchoalveolar lavage fluid (BALF) and mitigatingpulmonary histological alters, as well as hematological change. The MAPK and NF-κB signaling pathways in LPS-stimulated ALI mice were dampened by QFAE pretreatment, whereas AMPK signaling pathways were accelerated, as testify by significant restraint of phosphorylation of ERK, JNK, p38, p65, and IκBα, and distinct elevation of phosphorylation of ACC and AMPKα. The remarkable anti-inflammatory effect of QFAE is associated with the suppression of MAPK and NF-κB signaling pathways and the initiation of AMPK signaling pathway.
Circulating Tumor Cell Detection and Polyomavirus Status in Merkel Cell Carcinoma
Authors: Boyer Magali , Cayrefourcq Laure , Garima Françoise , Foulongne Vincent , Dereure Olivier , Alix-Panabières Catherine 
Published: January 2020

AbstractThe incidence of Merkel cell carcinoma (MCC), a rare and highly metastatic skin malignancy, has sharply increased in the last decade. Clinical biomarkers are urgently needed for MCC prognosis, treatment response monitoring, and early diagnosis of relapse. The clinical interest of circulating tumors cells (CTCs) has been validated in many solid cancers. The aim of this study was to compare CTC detection and characterization in blood samples of patients with MCC using the CellSearch System and the RosetteSep -DEPArray workflow, an innovative procedure to enrich, detect and isolate single CTCs. In preliminary experiments (using spiked MCC cell lines) both methods allowed detecting very few MCC cells. In blood samples from 19 patients with MCC at different stages, CellSearch detected MCC CTCs in 26% of patients, and the R-D workflow in 42% of patients. The detection of CTC-positive patients increased to 52% by the cumulative positivity rate of both methodologies. Moreover, Merkel cell polyomavirus DNA, involved in MCC oncogenesis, was detected in tumor biopsies, but not in all single CTCs from the same patient, reflecting the tumor heterogeneity. Our data demonstrate the possibility to detect, isolate and characterize CTCs in patients with MCC using two complementary approaches.