bluuebunny/crossref_metadata_2025 huggingface dataset:
VEGF-B ablation in pancreatic β-cells upregulates insulin expression without affecting glucose homeostasis or islet lipid uptake
Authors: Ning Frank Chenfei , Jensen Nina , Mi Jiarui , Lindström William , Balan Mirela , Muhl Lars , Eriksson Ulf , Nilsson Ingrid , Nyqvist Daniel
Published: January 2020

Type 2 diabetes mellitus (T2DM) affects millions of people and is linked with obesity and lipid accumulation in peripheral tissues. Increased lipid handling and lipotoxicity in insulin producing β-cells may contribute to β-cell dysfunction in T2DM. The vascular endothelial growth factor (VEGF)-B regulates uptake and transcytosis of long-chain fatty acids over the endothelium to tissues such as heart and skeletal muscle. Systemic inhibition of VEGF-B signaling prevents tissue lipid accumulation, improves insulin sensitivity and glucose tolerance, as well as reduces pancreatic islet triglyceride content, under T2DM conditions. To date, the role of local VEGF-B signaling in pancreatic islet physiology and in the regulation of fatty acid trans-endothelial transport in pancreatic islet is unknown. To address these questions, we have generated a mouse strain where VEGF-B is selectively depleted in β-cells, and assessed glucose homeostasis, β-cell function and islet lipid content under both normal and high-fat diet feeding conditions. We found that Vegfb was ubiquitously expressed throughout the pancreas, and that β-cell Vegfb deletion resulted in increased insulin gene expression. However, glucose homeostasis and islet lipid uptake remained unaffected by β-cell VEGF-B deficiency.
Hepatitis C virus infection suppresses hepatitis B virus replication via the RIG-I-like helicase pathway
Authors: Murai Kazuhiro , Hikita Hayato , Kai Yugo , Kondo Yasuteru , Fukuoka Makoto , Fukutomi Keisuke , Doi Akira , Yamai Takuo , Nakabori Tasuku , Fukuda Ryo , Takahashi Takeshi , Miyakawa Kei , Suemizu Hiroshi , Ryo Akihide , Yamada Ryoko , Kodama Takahiro , Sakamori Ryotaro , Tatsumi Tomohide , Takehara Tetsuo
Published: January 2020

Mechanisms of hepatitis B virus (HBV) reactivation after hepatitis C virus (HCV) elimination by direct-acting antiviral (DAA) treatment in HBV/HCV-co-infected patients remain unclear. We examined RIG-I-like helicase (RLH) pathway activation by HBV mono-infection, HCV mono-infection or HBV/HCV co-infection and interference between HBV and HCV in primary human hepatocytes. Interference between HBV and HCV and HBV reactivation after DAA treatment in humanized-liver mice were assessed. HCV infection activated RLH pathway, as evidenced by RIG-I, ISG15 and ISG56 expression induction; HBV caused only RIG-I induction in vitro. RLH activation was also found in HBV/HCV-co-infected cells, and HBV replication were suppressed in HBV/HCV-co-infected than in HBV-mono-infected cells. siRNA-mediated double knockdown of ISG15 and ISG56 increased HBV replication in HBV/HCV-co-infected cells. HCV infection activated RLH pathway and suppressed HBV replication in humanized-liver mice. Subsequent elimination of HCV by DAA administration downregulated RLH pathway and upregulated HBV replication in mice. RLH pathway was activated in livers of chronic hepatitis C patients compared to those of chronic hepatitis B or non-B, non-C patients. The RLH pathway activation was downregulated by HCV elimination. In conclusion, HCV infection activated RLH pathway and suppressed HBV replication in human hepatocytes. HCV elimination upregulated HBV replication, probably through RLH pathway downregulation.
Characterization of chitosan/alginate/lovastatin nanoparticles and investigation of their toxic effects in vitro and in vivo
Authors: Thai Hoang , Thuy Nguyen Chinh , Thi Thach Loc , Thi Tran Mai , Duc Mai Huynh , Thi Thu Nguyen Trang , Duc Le Giang , Van Can Mao , Dai Tran Lam , Long Bach Giang , Ramadass Kavitha , Sathish C. I. , Van Le Quan
Published: January 2020

In this study, chitosan and alginate were selected to prepare alginate/chitosan nanoparticles to load the drug lovastatin by the ionic gelation method. The synthesized nanoparticles loaded with drug were characterized by Fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), laser scattering and differential scanning calorimetry (DSC) methods. The FTIR spectrum of the alginate/chitosan/lovastatin nanoparticles showed that chitosan and alginate interacted with lovastatin through hydrogen bonding and dipolar-dipolar interactions between the C-O, C=O, and OH groups in lovastatin, the C-O, NH, and OH groups in chitosan and the C-O, C=O, and OH groups in alginate. The laser scattering results and SEM images indicated that the alginate/chitosan/lovastatin nanoparticles have a spherical shape with a particle size in the range of 50–80 nm. The DSC diagrams displayed that the melting temperature of the alginate/chitosan/lovastatin nanoparticles was higher than that of chitosan and lower than that of alginate. This result means that the alginate and chitosan interact together, so that the nanoparticles have a larger crystal degree when compared with alginate and chitosan individually. Investigations of thein vitrolovastatin release from the alginate/chitosan/lovastatin nanoparticles under different conditions, including different alginate/chitosan ratios, different solution pH values and different lovastatin contents, were carried out by ultraviolet-visible spectroscopy. The rate of drug release from the nanoparticles is proportional to the increase in the solution pH and inversely proportional to the content of the loaded lovastatin. The drug release process is divided into two stages: a rapid stage over the first 10 hr, then the release becomes gradual and stable. The Korsmeyer-Peppas model is most suitable for the lovastatin release process from the alginate/chitosan/lovastatin nanoparticles in the first stage, and then the drug release complies with other models depending on solution pH in the slow release stage. In addition, the toxicity of alginate/chitosan/lovastatin (abbreviated ACL) nanoparticles was sufficiently low in mice in the acute toxicity test. The LD50of the drug was higher than 5000 mg/kg, while in the subchronic toxicity test with treatments of 100 mg/kg and 300 mg/kg ACL nanoparticles, there were no abnormal signs, mortality, or toxicity in general to the function or structure of the crucial organs. The results show that the ACL nanoparticles are safe in mice and that these composite nanoparticles might be useful as a new drug carrier.
Elevated circulating CD14++CD16+ intermediate monocytes are independently associated with extracardiac complications after cardiac surgery
Authors: Mossanen Jana C. , Jansen Tobias U. , Pracht Jessica , Liepelt Anke , Buendgens Lukas , Stoppe Christian , Goetzenich Andreas , Simon Tim-Philipp , Autschbach Rüdiger , Marx Gernot , Tacke Frank
Published: January 2020

Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications. We therefore prospectively included 104 patients undergoing cardiac surgery in our study. We assessed peripheral blood leukocyte populations by flow cytometry and circulating cytokines before operation, after surgery and at days one and four post-operatively. Patients undergoing cardiac surgery showed significantly elevated leukocytes and neutrophils after surgery. On the contrary, monocytes decreased after surgery and significantly increased at days 1 and 4, particularly classical (Mon1,CD14++CD16−) and intermediate (Mon2,CD14++CD16+) monocytes. While peripheral leukocyte subsets were unaltered in patients with infectious (n = 15) or cardiac complications (n = 31), post-operative leukocytes (p = 0.0016), neutrophils (p = 0.0061) and Mon2 (p = 0.0007) were clearly raised in patients developing extracardiac complications (n = 35). Using multiple logistic regression analyses, patient’s age, ICU days, number of blood transfusions and elevated post-surgery Mon2 independently predicted extracardiac complications. Our findings demonstrate that elevated Mon2 after cardiac surgery are associated with an increased risk for extracardiac complications. These findings might improve the risk estimation after cardiac operations and the role of Mon2 for inflammation in cardiac surgery.
Emotional information affects fission illusion induced by audio-visual interactions
Authors: Takeshima Yasuhiro
Published: January 2020

Multisensory integration is affected by various types of information coming from different sensory stimuli. It has been suggested that emotional information also influences the multisensory integration process. The perceptual phenomena induced by audio-visual integration are modulated by emotional signals through changing individuals’ emotional states. However, the direct effects of emotional information, without changing emotional states on the multisensory integration process have not yet been examined. The present study investigated the effects of an emotional signal on audio-visual integration. The experiments compared the magnitude of audio-visual fission and fusion illusions using facial expression stimuli and simple geometric shapes. Facial expression stimuli altered the criterion difference for discerning the number of flashes when two beeps were simultaneously presented in Experiment 1. These stimuli did not affect the fission illusion’s magnitude. For simple geometric shapes, emotional shapes perceptually induced a larger fission illusion in Experiment 2. The present study found that the emotional valence included in simple geometric shapes induced a larger fission illusion. Moreover, current results suggest that emotional faces modulate response criterion for fission illusion in discernment of the number of flashes. Future studies should elucidate in detail the mechanism of emotional valence effects on audio-visual integration.
TDCS to the right anterior temporal lobe facilitates insight problem-solving
Authors: Salvi Carola , Beeman Mark , Bikson Marom , McKinley Richard , Grafman Jordan
Published: January 2020

Problem-solving is essential for advances in cultural, social, and scientific knowledge. It is also one of the most challenging cognitive processes to facilitate. Some problem-solving is deliberate, but frequently people solve problems with a sudden insight, also known as a Eureka or “Aha!” moment. The advantage of solving problems via insight is that these solutions are more accurate, relying on a unique pattern of neural activity, compared to deliberative strategies. The right Anterior Temporal Lobe (rATL), putatively involved in semantic integration, is distinctively activated when people experience an insight. The rATL may contribute to the recognition of distant semantic relations that support insight solutions, although fMRI and EEG evidence for its involvement is, by nature, correlational. In this study, we investigate if focal sub-threshold neuromodulation to the rATL facilitates insight problem-solving. In three different groups, using a within- and between-subjects design, we tested the causal role of this brain region in problem-solving, by applying High Definition Transcranial Direct Current Stimulation to the rATL (active and sham condition) or the left frontopolar region while participants attempted to solve Compound Remote Associates problems before, during and after stimulation. Participants solved a higher percentage of problems, overall, and specifically by insight when they received rATL stimulation, compared to pre-stimulation, and compared to sham and left frontopolar stimulation. These results confirm the crucial role played by the rATL in insight problem-solving.
Endometrial preparation for frozen-thawed embryo transfer in an artificial cycle: transdermal versus vaginal estrogen
Authors: Corroenne Romain , El Hachem Hady , Verhaeghe Caroline , Legendre Guillaume , Dreux Cecile , Jeanneteau Pauline , Descamps Philippe , May-Panloup Pascale , Bouet Pierre-Emmanuel
Published: January 2020

The objective was to compare the endometrial thickness (ET) in a frozen embryo transfer (FET) cycle between transdermal and vaginal estrogen. Our secondary objectives were to compare the patient satisfaction and the pregnancy outcomes. Prospective monocentric cohort study between 01/2017 and 12/2017 at a single institution. Choice of administration was left to the patient. 119 cycles had transdermal estrogen (T-group) and 199 had vaginal estrogen (V-group). The ET at 10 ± 1 days of treatment was significantly higher in the T-group compared to the V-group (9.9 vs 9.3 mm, p = 0.03). In the T-group, the mean duration of treatment was shorter (13.6 vs 15.5 days, p < 0.001). The rate of cycle cancelation was comparable between the two groups (12.6% vs 8.5%, p = 0.24). Serum estradiol levels were significantly lower (268 vs 1332 pg/ml, p < 0.001), and serum LH levels were significantly higher (12.1 ± 16.5 vs 5 ± 7.5 mIU/ml, p < 0.001) in the T-group. Patient satisfaction was higher in the T-group (p = 0.04) and 85.7% (36/42) of women who had received both treatments preferred the transdermal over the vaginal route. Live birth rates were comparable between the two groups (18% vs 19%, p = 0.1). Transdermal estrogen in artificial FET cycles was associated with higher ET, shorter treatment duration and better tolerance.
Comparative Analysis of the Discriminatory Performance of Different Well-Known Risk Assessment Scores for Extended Hepatectomy
Authors: Ghamarnejad Omid , Khajeh Elias , Rezaei Nahid , Afshari Khashayar , Adelian Ali , Nikdad Mohammadsadegh , Hoffmann Katrin , Mehrabi Arianeb
Published: January 2020

The aim of this study was to assess and compare the discriminatory performance of well-known risk assessment scores in predicting mortality risk after extended hepatectomy (EH). A series of 250 patients who underwent EH (≥5 segments resection) were evaluated. Aspartate aminotransferase-to-platelet ratio index (APRI), albumin to bilirubin (ALBI) grade, predictive score developed by Breitenstein et al., liver fibrosis (FIB-4) index, and Heidelberg reference lines charting were used to compute cut-off values, and the sensitivity and specificity of each risk assessment score for predicting mortality were also calculated. Major morbidity and 90-day mortality after EH increased with increasing risk scores. APRI (86%), ALBI (86%), Heidelberg score (81%), and FIB-4 index (79%) had the highest sensitivity for 90-day mortality. However, only the FIB-4 index and Heidelberg score had an acceptable specificity (70% and 65%, respectively). A two-stage risk assessment strategy (Heidelberg–FIB-4 model) with a sensitivity of 70% and a specificity 86% for 90-day mortality was proposed. There is no single specific risk assessment score for patients who undergo EH. A two-stage screening strategy using Heidelberg score and FIB-4 index was proposed to predict mortality after major liver resection.
Mechanical forces induce an asthma gene signature in healthy airway epithelial cells
Authors: Kılıç Ayşe , Ameli Asher , Park Jin-Ah , Kho Alvin T. , Tantisira Kelan , Santolini Marc , Cheng Feixiong , Mitchel Jennifer A. , McGill Maureen , O’Sullivan Michael J. , De Marzio Margherita , Sharma Amitabh , Randell Scott H. , Drazen Jeffrey M. , Fredberg Jeffrey J. , Weiss Scott T.
Published: January 2020

Bronchospasm compresses the bronchial epithelium, and this compressive stress has been implicated in asthma pathogenesis. However, the molecular mechanisms by which this compressive stress alters pathways relevant to disease are not well understood. Using air-liquid interface cultures of primary human bronchial epithelial cells derived from non-asthmatic donors and asthmatic donors, we applied a compressive stress and then used a network approach to map resulting changes in the molecular interactome. In cells from non-asthmatic donors, compression by itself was sufficient to induce inflammatory, late repair, and fibrotic pathways. Remarkably, this molecular profile of non-asthmatic cells after compression recapitulated the profile of asthmatic cells before compression. Together, these results show that even in the absence of any inflammatory stimulus, mechanical compression alone is sufficient to induce an asthma-like molecular signature.
A high sensitivity ZENK monoclonal antibody to map neuronal activity in Aves
Authors: Nordmann Gregory Charles , Malkemper Erich Pascal , Landler Lukas , Ushakova Lyubov , Nimpf Simon , Heinen Robert , Schuechner Stefan , Ogris Egon , Keays David Anthony
Published: January 2020

The transcription factor ZENK is an immediate early gene that has been employed as a surrogate marker to map neuronal activity in the brain. It has been used in a wide variety of species, however, commercially available antibodies have limited immunoreactivity in birds. To address this issue we generated a new mouse monoclonal antibody, 7B7-A3, raised against ZENK from the rock pigeon (Columba livia). We show that 7B7-A3 labelsclZENK in both immunoblots and histological stainings with high sensitivity and selectivity for its target. Using a sound stimulation paradigm we demonstrate that 7B7-A3 can detect activity-dependent ZENK expression at key stations of the central auditory pathway of the pigeon. Finally, we compare staining efficiency across three avian species and confirm that 7B7-A3 is compatible with immunohistochemical detection of ZENK in the rock pigeon, zebra finch, and domestic chicken. Taken together, 7B7-A3 represents a useful tool for the avian neuroscience community to map functional activity in the brain.
Resident and phytometer plants host comparable rhizosphere fungal communities in managed grassland ecosystems
Authors: Schöps Ricardo , Goldmann Kezia , Korell Lotte , Bruelheide Helge , Wubet Tesfaye , Buscot François
Published: January 2020

Plants are known to modulate their own rhizosphere mycobiome. However, field studies that use resident plants to relate the microbiome assemblage to environmental factors such as land-use suffer from the problem that confounding factors such as plant age and performance may override the targeted effects. In contrast, the use of even-aged phytometer plants pre-cultivated under uniform conditions helps to reduce such random variation. We investigated the rhizosphere mycobiomes of phytometer and resident plants of two common grassland species, Dactylis glomerata L. s. str. and Plantago lanceolata L. along a land-use intensity gradient using ITS rRNA Illumina amplicon sequencing. Remarkably, we did not detect effects of the plant types (resident vs. phytometer plant, even though some fungal taxa exhibited plant species specificity), indicating that phytometer plants hosted a comparable rhizosphere mycobiome as resident plants. Our data indicate that the plant species harbor distinct fungal communities, with fungal richness in the rhizosphere of P. lanceolata being substantially higher than that of D. glomerata. Land-use intensity had a clear impact on the mycobiome of both plant species, with specific fungal genera showing differential tolerance to high intensities. Overall, the phytometer approach has a high potential to reveal environmental impacts on rhizosphere communities.
The antibiotic vancomycin induces complexation and aggregation of gastrointestinal and submaxillary mucins
Authors: Dinu Vlad , Lu Yudong , Weston Nicola , Lithgo Ryan , Coupe Hayley , Channell Guy , Adams Gary G. , Torcello Gómez Amelia , Sabater Carlos , Mackie Alan , Parmenter Christopher , Fisk Ian , Phillips-Jones Mary K. , Harding Stephen E.
Published: January 2020

Vancomycin, a branched tricyclic glycosylated peptide antibiotic, is a last-line defence against serious infections caused by staphylococci, enterococci and other Gram-positive bacteria. Orally-administered vancomycin is the drug of choice to treat pseudomembranous enterocolitis in the gastrointestinal tract. However, the risk of vancomycin-resistant enterococcal infection or colonization is significantly associated with oral vancomycin. Using the powerful matrix-free assay of co-sedimentation analytical ultracentrifugation, reinforced by dynamic light scattering and environmental scanning electron microscopy, and with porcine mucin as the model mucin system, this is the first study to demonstrate strong interactions between vancomycin and gastric and intestinal mucins, resulting in very large aggregates and depletion of macromolecular mucin and occurring at concentrations relevant to oral dosing. In the case of another mucin which has a much lower degree of glycosylation (~60%) – bovine submaxillary mucin - a weaker but still demonstrable interaction is observed. Our demonstration - for the first time - of complexation/depletion interactions for model mucin systems with vancomycin provides the basis for further study on the implications of complexation on glycopeptide transit in humans, antibiotic bioavailability for target inhibition, in situ generation of resistance and future development strategies for absorption of the antibiotic across the mucus barrier.
Effects of microtubule-inhibiting small molecule and antibody-drug conjugate treatment on differentially-sized A431 squamous carcinoma spheroids
Authors: Durbin Kenneth R. , Nottoli M. Shannon , Jenkins Gary J.
Published: January 2020

Multicellular tumor spheroids have been increasingly used by researchers to produce more physiologically relevant experimental environments. However, tracking of spheroid growth and treatment-induced volume reduction has not been readily adopted. Here, squamous carcinoma cells were seeded at different starting cell numbers with growth and reduction kinetics monitored using live cell imaging. Following the initial growth phase, spheroids were treated with auristatin as small molecule (MMAE) or as antibody-drug conjugate containing non-cleavable auristatin drug payload (033-F). Compared to cells in monolayers, 033-F had notably weaker potency against spheroids despite potency levels of MMAE being similar against monolayers and spheroids. Accumulation of released payload from 033-F was reduced in higher volume spheroids, likely contributing to the potency differences. Despite lowered potency towards spheroids with 033-F, spheroid volume was still readily reduced by 033-F in a dose-dependent fashion, with >85% volume reductions at the highest concentrations for all spheroid sizes. Additionally, the core of the larger spheroids showed more resiliency towards microtubule inhibition. Overall, this work highlights how various in-vivo ‘features’ such as tumor penetration, cell interactions, and increased resistance to therapeutics can be integrated into a spheroid model and tracked over time by automated imaging technology.
Magnetic Resonance Microscopy at Cellular Resolution and Localised Spectroscopy of Medicago truncatula at 22.3 Tesla
Authors: van Schadewijk Remco , Krug Julia R. , Shen Defeng , Sankar Gupta Karthick B. S. , Vergeldt Frank J. , Bisseling Ton , Webb Andrew G. , Van As Henk , Velders Aldrik H. , de Groot Huub J. M. , Alia A.
Published: January 2020

Interactions between plants and the soil’s microbial & fungal flora are crucial for the health of soil ecosystems and food production. Microbe-plant interactions are difficult to investigate in situ due to their intertwined relationship involving morphology and metabolism. Here, we describe an approach to overcome this challenge by elucidating morphology and the metabolic profile of Medicago truncatula root nodules using Magnetic Resonance (MR) Microscopy, at the highest magnetic field strength (22.3 T) currently available for imaging. A home-built solenoid RF coil with an inner diameter of 1.5 mm was used to study individual root nodules. A 3D imaging sequence with an isotropic resolution of (7 μm)3 was able to resolve individual cells, and distinguish between cells infected with rhizobia and uninfected cells. Furthermore, we studied the metabolic profile of cells in different sections of the root nodule using localised MR spectroscopy and showed that several metabolites, including betaine, asparagine/aspartate and choline, have different concentrations across nodule zones. The metabolite spatial distribution was visualised using chemical shift imaging. Finally, we describe the technical challenges and outlook towards future in vivo MR microscopy of nodules and the plant root system.
Tannic acid inhibits lipid metabolism and induce ROS in prostate cancer cells
Authors: Nagesh Prashanth K. B. , Chowdhury Pallabita , Hatami Elham , Jain Shashi , Dan Nirnoy , Kashyap Vivek Kumar , Chauhan Subhash C. , Jaggi Meena , Yallapu Murali M.
Published: January 2020

Prostate cancer (PCa) cells exploit the aberrant lipid signaling and metabolism as their survival advantage. Also, intracellular storage lipids act as fuel for the PCa proliferation. However, few studies were available that addressed the topic of targeting lipid metabolism in PCa. Here, we assessed the tannic acid (TA) lipid-targeting ability and its capability to induce endoplasmic reticulum (ER) stress by reactive oxygen species (ROS) in PCa cells. TA exhibited dual effects by inhibiting lipogenic signaling and suppression of lipid metabolic pathways. The expression of proteins responsible for lipogenesis was down regulated. The membrane permeability and functionality of PCa were severely affected and caused nuclear disorganization during drug exposure. Finally, these consolidated events shifted the cell’s survival balance towards apoptosis. These results suggest that TA distinctly interferes with the lipid signaling and metabolism of PCa cells.
Behavioral characterization of a CRISPR-generated TRPA1 knockout rat in models of pain, itch, and asthma
Authors: Reese Rebecca M. , Dourado Michelle , Anderson Keith , Warming Søren , Stark Kimberly L. , Balestrini Alessia , Suto Eric , Lee Wyne , Riol-Blanco Lorena , Shields Shannon D. , Hackos David H.
Published: January 2020

The transient receptor potential (TRP) superfamily of ion channels has garnered significant attention by the pharmaceutical industry. In particular, TRP channels showing high levels of expression in sensory neurons such as TRPV1, TRPA1, and TRPM8, have been considered as targets for indications where sensory neurons play a fundamental role, such as pain, itch, and asthma. Modeling these indications in rodents is challenging, especially in mice. The rat is the preferred species for pharmacological studies in pain, itch, and asthma, but until recently, genetic manipulation of the rat has been technically challenging. Here, using CRISPR technology, we have generated a TRPA1 KO rat to enable more sophisticated modeling of pain, itch, and asthma. We present a detailed phenotyping of the TRPA1 KO rat in models of pain, itch, and asthma that have previously only been investigated in the mouse. With the exception of nociception induced by direct TRPA1 activation, we have found that the TRPA1 KO rat shows apparently normal behavioral responses in multiple models of pain and itch. Immune cell infiltration into the lung in the rat OVA model of asthma, on the other hand, appears to be dependent on TRPA1, similar to was has been observed in TRPA1 KO mice. Our hope is that the TRPA1 KO rat will become a useful tool in further studies of TRPA1 as a drug target.
Analysis of Copy-Number Variations and Feline Mammary Carcinoma Survival
Authors: Granados-Soler José Luis , Bornemann-Kolatzki Kirsten , Beck Julia , Brenig Bertram , Schütz Ekkehard , Betz Daniela , Junginger Johannes , Hewicker-Trautwein Marion , Murua Escobar Hugo , Nolte Ingo
Published: January 2020

Feline mammary carcinomas (FMCs) are highly malignant. As the disease-free survival (DFS) and overall survival (OS) are short, prognostication is crucial. Copy-number variations (CNVs) analysis by next-generation sequencing serves to identify critical cancer-related genomic regions. Thirty-three female cats with FMCs were followed during two years after surgery. Tumours represented tubulopapillary and solid carcinomas encompassing six molecular subtypes. Regardless of the histopathological diagnosis, molecular subtypes showed important differences in survival. Luminal A tumours exhibited the highest DFS (p = 0.002) and cancer-specific OS (p = 0.001), and the lowest amount of CNVs (p = 0.0001). In contrast, basal-like triple-negative FMCs had the worst outcome (DFS, p < 0.0001; and OS, p < 0.00001) and were the most aberrant (p = 0.05). In the multivariate analysis, copy-number losses (CNLs) in chromosome B1 (1–23 Mb) harbouring several tumour-repressors (e.g. CSMD1, MTUS1, MSR1, DBC2, and TUSC3) negatively influenced DFS. Whereas, copy-number gains (CNGs) in B4 (1–29 Mb) and F2 (64–82.3 Mb) comprising epithelial to mesenchymal transition genes and metastasis-promoting transcription factors (e.g. GATA3, VIM, ZEB1, and MYC) negatively influenced DFS and cancer-specific OS. These data evidence an association between specific CNVs in chromosomes B1, B4 and F2, and poor prognosis in FMCs.
Intrinsic sensory disinhibition contributes to intrusive re-experiencing in combat veterans
Authors: Clancy Kevin J. , Albizu Alejandro , Schmidt Norman B. , Li Wen
Published: January 2020

Intrusive re-experiencing of traumatic events is a hallmark symptom of posttraumatic stress disorder, characterized by rich and vivid sensory details as reported in “flashbacks”. While prevailing models of trauma intrusions focus on dysregulated emotional processes, we hypothesize that a deficiency in intrinsic sensory inhibition could drive overactivation of sensory representations of trauma memories, precipitating sensory-rich intrusions. In a sample of combat veterans, we examined resting-state alpha (8–12 Hz) oscillatory activity (in both power and posterior→frontal connectivity), given its role in sensory cortical inhibition, in association with intrusive re-experiencing symptoms. Veterans further participated in an odor task (including both combat and non-combat odors) to assess olfactory trauma memory and emotional response. We observed an association between intrusive re-experiencing symptoms and attenuated resting-state posterior→frontal alpha connectivity, which were both correlated with olfactory trauma memory. Importantly, olfactory trauma memory was identified as a mediator of the relationship between alpha connectivity and intrusive re-experiencing, suggesting that deficits in intrinsic sensory inhibition contributed to intrusive re-experiencing of trauma via heightened trauma memory. Therefore, by permitting unfiltered sensory cues to enter information processing and activate sensory representations of trauma, sensory disinhibition can constitute a sensory mechanism of intrusive re-experiencing in trauma-exposed individuals.
Treatment of Coral Wounds by Combining an Antiseptic Bilayer Film and an Injectable Antioxidant Biopolymer
Authors: Contardi Marco , Montano Simone , Liguori Giulia , Heredia-Guerrero José A. , Galli Paolo , Athanassiou Athanassia , Bayer Ilker S.
Published: January 2020

Coral reefs are vital for the marine ecosystem and their potential disappearance can have unequivocal consequences on our environment. Aside from pollution-related threats (changes in water temperature, plastics, and acidity), corals can be injured by diseases, predators, humans and other invasive species. Diseases play an important role in this decline, but so far very few mitigation strategies have been proposed and developed to control this threat. In this work, we demonstrate that recently developed bi-layer human skin wound treatment patches containing antiseptics and natural antioxidants with controlled-release capacity can be adapted to treat scleractinian coral wounds effectively. A hydrophilic bilayer film based on polyvinylpyrrolidone (PVP) and hyaluronic acid was used to cover the open wounds while delivering the antiseptics for rapid action. Afterwards, the hydrophilic bi-layer covered wound was sealed with an antioxidant and hydrophobic ε-caprolactone-p-coumaric acid copolymer by melt injection at low temperatures. Treated coral injuries were monitored both in aquaria system and in natural environment in Maldives for over 4 months to reduce the number of entry points for organisms that could lead to diseases. The corals well-tolerated both biomaterials as well as the antiseptics incorporated in these materials. The treatments displayed self-adhering properties, tuneable dissolution time, and biocompatibility and stimulated regeneration properties within the coral wound. As such, this work demonstrates that certain human skin wound treatment materials can be successfully adapted to the curing of coral wounds and delivery of specific drugs to slow down, reduce or even stop the spread of diseases in scleractinian corals as well as in all other benthic organisms affected by uncontrolled pathologies.
AMPA receptor-mTORC1 signaling activation is required for neuroplastic effects of LY341495 in rat hippocampal neurons
Authors: Seo Mi kyoung , Hien Le Thi , Park Min Kyung , Choi Ah Jeong , Seog Dae-Hyun , Kim Seong-Ho , Park Sung Woo , Lee Jung Goo
Published: January 2020

The group II metabotropic glutamate 2/3 (mGlu2/3) receptor antagonist LY341495 produces antidepressant-like effects by acting on mammalian target of rapamycin complex 1 (mTORC1) signaling and α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors in rodent. We investigated whether LY341495 affects neuroplasticity via these mechanisms in rat primary hippocampal cultures under conditions of dexamethasone (DEX)-induced neurotoxicity. Ketamine was used for comparison. Hippocampal cultures were treated with LY341495 under conditions of DEX-induced toxicity. Changes in mTORC1-mediated proteins were determined by Western blotting analyses. Changes in dendritic outgrowth and spine density were evaluated via immunostaining. LY341495 significantly prevented DEX-induced decreases in the levels of mTORC1, 4E-BP1, and p70S6K phosphorylation as well as the levels of the synaptic proteins. These effects were blocked by pretreatment with the AMPA receptor inhibitor 2,3-dihydroxy-6-nitro-7sulfamoyl-benzo(f)quinoxaline (NBQX) and the mTORC1 inhibitor rapamycin. LY341495 significantly attenuated DEX-induced decreases in dendritic outgrowth and spine density. Pretreatment with rapamycin and NBQX blocked these effects of LY341495. Further analyses indicted that induction of BDNF expression produced by LY341495 was blocked by pretreatment with NBQX and rapamycin. LY341495 has neuroplastic effects by acting on AMPA receptor-mTORC1 signaling under neurotoxic conditions. Therefore, activation of AMPA receptor and mTORC1 signaling, which enhance neuroplasticity, may be novel targets for new antidepressants.
Lower Systolic Blood Pressure in Normotensive Subjects is Related to Better Autonomic Recovery Following Exercise
Authors: de Oliveira Letícia Santana , Fontes Anne Michelli G. G. , Vitor Ana Laura Ricci , Vanderlei Franciele M. , Garner David M. , Valenti Vitor E.
Published: January 2020

Blood pressure (BP) is a cardiovascular parameter applied to detect cardiovascular risk. Recently, the pre-hypertension state has received greater consideration for prevention strategies. We evaluated autonomic and cardiorespiratory recovery following aerobic exercise in normotensive individuals with different systolic BP (SBP) values. We investigated 30 healthy men aged 18 to 30 years divided into groups according to systolic BP (SBP): G1 (n = 16), resting SBP <110 mmHg and G2 (n = 14), resting SBP between 120–110 mmHg. The groups endured 15 minutes seated at rest, followed by a submaximal aerobic exercise on a treadmill and then remaining seated for 60 minutes also at rest, during recovery from the exercise. Cardiorespiratory parameters and heart rate (HR) variability (HRV) (rMSSD, SD1, HF [ms2]) were evaluated before and during recovery from exercise. G2 displayed slower return of SBP, rMSSD and SD1 HRV indices during recovery from exercise compared to G1. In conclusion, normotensive subjects with higher resting SBP (110 to 120 mmHg) offered delayed autonomic recovery following moderate exercise. We suggest that this group may be less physiologically optimized leading to cardiac risks.
Measuring the spatial heterogeneity on the reduction of vaginal fistula burden in Ethiopia between 2005 and 2016
Authors: Deribe Kebede , Fronterre Claudio , Dejene Tariku , Biadgilign Sibhatu , Deribew Amare , Abdullah Muna , Cano Jorge
Published: January 2020

Vaginal fistula is a shattering maternal complication characterized by an anomalous opening between the bladder and/or rectum and vagina resulting in continuous leakage of urine or stool. Although prevalent in Ethiopia, its magnitude and distribution is not well studied. We used statistical mapping models using 2005 and 2016 Ethiopia Demographic Health Surveys data combined with a suite of potential risk factors to estimate the burden of vaginal fistula among women of childbearing age. The estimated number of women of childbearing age with lifetime and untreated vaginal fistula in 2016 were 72,533 (95% CI 38,235–124,103) and 31,961 (95% CI 11,596–70,309) respectively. These figures show reduction from the 2005 estimates: 98,098 (95% CI 49,819–170,737) lifetime and 59,114 (95% CI 26,580–118,158) untreated cases of vaginal fistula. The number of districts having more than 200 untreated cases declined drastically from 54 in 2005 to 6 in 2016. Our results show a significant subnational variation in the burden of vaginal fistula. Overall, between 2005 and 2016 there was substantial reduction in the prevalence of vaginal fistula in Ethiopia. Our results help guide local level tracking, planning, spatial targeting of resources and implementation of interventions against vaginal fistula.
Author Correction: Involvement of Hsp90 and cyclophilins in intoxication by AIP56, a metalloprotease toxin from Photobacterium damselae subsp. piscicida
Authors: Rodrigues Inês S. , pereira Liliana M. G. , Lisboa Johnny , Pereira Cassilda , Oliveira Pedro , Santos Nuno M. S. dos , Vale Ana do
Published: January 2020

An amendment to this paper has been published and can be accessed via a link at the top of the paper.
Biotin proximity tagging favours unfolded proteins and enables the study of intrinsically disordered regions
Authors: Minde David-Paul , Ramakrishna Manasa , Lilley Kathryn S.
Published: January 2020

Intrinsically Disordered Regions (IDRs) are enriched in disease-linked proteins known to have multiple post-translational modifications, but there is limited in vivo information about how locally unfolded protein regions contribute to biological functions. We reasoned that IDRs should be more accessible to targeted in vivo biotinylation than ordered protein regions, if they retain their flexibility in human cells. Indeed, we observed increased biotinylation density in predicted IDRs in several cellular compartments >20,000 biotin sites from four proximity proteomics studies. We show that in a biotin ‘painting’ time course experiment, biotinylation events in Escherichia coli ribosomes progress from unfolded and exposed regions at 10 s, to structured and less accessible regions after five minutes. We conclude that biotin proximity tagging favours sites of local disorder in proteins and suggest the possibility of using biotin painting as a method to gain unique insights into in vivo condition-dependent subcellular plasticity of proteins.
Concurrent human TMS-EEG-fMRI enables monitoring of oscillatory brain state-dependent gating of cortico-subcortical network activity
Authors: Peters Judith C. , Reithler Joel , Graaf Tom A. de , Schuhmann Teresa , Goebel Rainer , Sack Alexander T.
Published: January 2020

Despite growing interest, the causal mechanisms underlying human neural network dynamics remain elusive. Transcranial Magnetic Stimulation (TMS) allows to noninvasively probe neural excitability, while concurrent fMRI can log the induced activity propagation through connected network nodes. However, this approach ignores ongoing oscillatory fluctuations which strongly affect network excitability and concomitant behavior. Here, we show that concurrent TMS-EEG-fMRI enables precise and direct monitoring of causal dependencies between oscillatory states and signal propagation throughout cortico-subcortical networks. To demonstrate the utility of this multimodal triad, we assessed how pre-TMS EEG power fluctuations influenced motor network activations induced by subthreshold TMS to right dorsal premotor cortex. In participants with adequate motor network reactivity, strong pre-TMS alpha power reduced TMS-evoked hemodynamic activations throughout the bilateral cortico-subcortical motor system (including striatum and thalamus), suggesting shunted network connectivity. Concurrent TMS-EEG-fMRI opens an exciting noninvasive avenue of subject-tailored network research into dynamic cognitive circuits and their dysfunction.
Quantification of aminobutyric acids and their clinical applications as biomarkers for osteoporosis
Authors: Wang Zhiying , Bian Liangqiao , Mo Chenglin , Shen Hui , Zhao Lan Juan , Su Kuan-Jui , Kukula Maciej , Lee Jauh Tzuoh , Armstrong Daniel W. , Recker Robert , Lappe Joan , Bonewald Lynda F. , Deng Hong-Wen , Brotto Marco
Published: January 2020

Osteoporosis is a highly prevalent chronic aging-related disease that frequently is only detected after fracture. We hypothesized that aminobutyric acids could serve as biomarkers for osteoporosis. We developed a quick, accurate, and sensitive screening method for aminobutyric acid isomers and enantiomers yielding correlations with bone mineral density (BMD) and osteoporotic fracture. In serum, γ-aminobutyric acid (GABA) and (R)-3-aminoisobutyric acid (D-BAIBA) have positive associations with physical activity in young lean women.D-BAIBA positively associated with hip BMD in older individuals without osteoporosis/osteopenia. Lower levels of GABA were observed in 60–80 year old women with osteoporotic fractures. Single nucleotide polymorphisms in seven genes related to these metabolites associated with BMD and osteoporosis. In peripheral blood monocytes, dihydropyrimidine dehydrogenase, an enzyme essential toD-BAIBA generation, exhibited positive association with physical activity and hip BMD. Along with their signaling roles, BAIBA and GABA might serve as biomarkers for diagnosis and treatments of osteoporosis.
Computational discovery of molecular C60 encapsulants with an evolutionary algorithm
Authors: Miklitz Marcin , Turcani Lukas , Greenaway Rebecca L. , Jelfs Kim E.
Published: January 2020

Computation is playing an increasing role in the discovery of materials, including supramolecular materials such as encapsulants. In this work, a function-led computational discovery using an evolutionary algorithm is used to find potential fullerene (C60) encapsulants within the chemical space of porous organic cages. We find that the promising host cages for C60 evolve over the simulations towards systems that share features such as the correct cavity size to host C60, planar tri-topic aldehyde building blocks with a small number of rotational bonds, di-topic amine linkers with functionality on adjacent carbon atoms, high structural symmetry, and strong complex binding affinity towards C60. The proposed cages are chemically feasible and similar to cages already present in the literature, helping to increase the likelihood of the future synthetic realisation of these predictions. The presented approach is generalisable and can be tailored to target a wide range of properties in molecular material systems.
Understanding the redox process upon electrochemical cycling of the P2-Na0.78Co1/2Mn1/3Ni1/6O2 electrode material for sodium-ion batteries
Authors: Hakim Charifa , Sabi Noha , Ma Le Anh , Dahbi Mouad , Brandell Daniel , Edström Kristina , Duda Laurent C. , Saadoune Ismael , Younesi Reza
Published: January 2020

Rechargeable sodium-ion batteries have recently attracted renewed interest as an alternative to Li-ion batteries for electric energy storage applications, because of the low cost and wide availability of sodium resources. Thus, the electrochemical energy storage community has been devoting increased attention to designing new cathode materials for sodium-ion batteries. Here we investigate P2- Na0.78Co1/2Mn1/3Ni1/6O2 as a cathode material for sodium ion batteries. The main focus is to understand the mechanism of the electrochemical performance of this material, especially differences observed in redox reactions at high potentials. Between 4.2 V and 4.5 V, the material delivers a reversible capacity which is studied in detail using advanced analytical techniques. In situ X-ray diffraction reveals the reversibility of the P2-type structure of the material. Combined soft X-ray absorption spectroscopy and resonant inelastic X-ray scattering demonstrates that Na deintercalation at high voltages is charge compensated by formation of localized electron holes on oxygen atoms.
Nucleoside-modified AdoMet analogues for differential methyltransferase targeting
Authors: Cornelissen Nicolas V. , Michailidou Freideriki , Muttach Fabian , Rau Kristina , Rentmeister Andrea
Published: January 2020

Methyltransferases modify a wide range of biomolecules using S-adenosyl-l-methionine (AdoMet) as cosubstrate. Enzymatic generation of nucleoside-modified AdoMet analogues and conversion by different methyltransferases is shown.
Nanosheet-assembled hierarchical flower-like g-C3N4 for enhanced photocatalytic CO2 reduction activity
Authors: Li Fang , Zhang Dainan , Xiang Quanjun
Published: January 2020

Nanosheet-assembled hierarchical flower-like g-C3N4 prepared by a molecular self-assembly and ethanol insertion strategy shows enhanced photocatalytic CO2 reduction activity.
Switching enzyme activity by a temperature responsive inhibitor modified polymer
Authors: Rottke Falko O. , Heyne Marie-Victoria , Reinicke Stefan
Published: January 2020

A thermoresponsive NIPAAm-based polymer is combined with the selective acetylcholinesterase inhibitor tacrine in order to create a strict in sense on/off switch for enzyme activity.
A fluorescent naphthalimide NADH mimic for continuous and reversible sensing of cellular redox state
Authors: Sharma Hemant , Tan Nian Kee , Trinh Natalie , Yeo Jia Hao , New Elizabeth J. , Pfeffer Frederick M.
Published: January 2020

A new naphthalimide based NADH mimic that functions as a fully reversible fluorescent “on off” probe for redox state has been synthesised and evaluated.
Electron transfer in a semiconductor heterostructure interface through electrophoretic deposition and a linker-assisted method
Authors: Zhou Yufeng , Tong Xin , Benetti Daniele , Wang Zhiming M. , Ma Dongling , Zhao Haiguang , Rosei Federico
Published: January 2020

Modulating the heterostructured interface of semiconductor nanocrystals is being widely explored to enhance the charge transfer rate in photoelectrochemical cells.
Luminescence of mononuclear Pt(ii) complexes with glycolate: external stimuli-induced excimer emission changes to oligomer emissions
Authors: Ohno Keiji , Komuro Masaya , Sugaya Tomoaki , Nagasawa Akira , Fujihara Takashi
Published: January 2020

Trihydrate crystals of novel PtII complexes [PtII(bpy)(gl)] (bpy: 2,2′-bipyridine; Hgl−: glycolate) show excimer emission changes to two kinds of oligomer emissions depending on the type of external stimuli.
Ir- and Ru-doped layered double hydroxides as affordable heterogeneous catalysts for electrochemical water oxidation
Authors: Fagiolari Lucia , Zaccaria Francesco , Costantino Ferdinando , Vivani Riccardo , Mavrokefalos Christos K. , Patzke Greta R. , Macchioni Alceo
Published: January 2020

Doping low-cost LDHs with noble metal atoms represents a promising approach to develop effective heterogeneous Water Oxidation Catalysts.
Fluorination and reduction of CaCrO3 by topochemical methods
Authors: Juillerat Christian A. , Tsujimoto Yoshihiro , Chikamatsu Akira , Masubuchi Yuji , Hasegawa Tetsuya , Yamaura Kazunari
Published: January 2020

CaCrO3 synthesized by high pressure methods is topochemically treated with polyvinylidene difluoride and undergoes stepwise reduction followed by fluorine incorporation.