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Felix Weissenberger, Marcelo Matheus Gauy, Johannes Lengler, Florian Meier, Angelika Steger
In computational neuroscience, synaptic plasticity rules are often formulated in terms of firing rates. The predominant description of in vivo neuronal activity, however, is the instantaneous rate (or spiking probability). In this article we resolve this discrepancy by showing that fluctuations of the membrane potential carry enough information to permit a precise estimate of the instantaneous rate in balanced networks. As a consequence, we find that rate based plasticity rules are not restricted to neuronal activity that is stable for hundreds of milliseconds to seconds, but can be carried over to situations in which it changes every few milliseconds...
March 15, 2018: Scientific Reports
Natalia M Vior, Rodney Lacret, Govind Chandra, Siobhán Dorai-Raj, Martin Trick, Andrew W Truman
Bicyclomycin (BCM) is a clinically promising antibiotic that is biosynthesised by Streptomyces cinnamoneus DSM 41675. BCM is structurally characterized by a core cyclo(L-Ile-L-Leu) 2,5-diketopiperazine (DKP) that is extensively oxidized. Here, we identify the BCM biosynthetic gene cluster, which shows that the core of BCM is biosynthesised by a cyclodipeptide synthase and the oxidative modifications are introduced by five 2-oxoglutarate-dependent dioxygenases and one cytochrome P450 monooxygenase. The discovery of the gene cluster enabled the identification of BCM pathways encoded in the genomes of hundreds of Pseudomonas aeruginosa isolates distributed globally, and heterologous expression of the pathway from P...
March 2, 2018: Applied and Environmental Microbiology
Guido Giunti, Vasiliki Mylonopoulou, Octavio Rivera Romero
BACKGROUND: Multiple sclerosis (MS) is one of the world's most common neurologic disorders. Fatigue is one of most common symptoms that persons with MS experience, having significant impact on their quality of life and limiting their activity levels. Self-management strategies are used to support them in the care of their health. Mobile health (mHealth) solutions are a way to offer persons with chronic conditions tools to successfully manage their symptoms and problems. Gamification is a current trend among mHealth apps used to create engaging user experiences and is suggested to be effective for behavioral change...
March 2, 2018: JMIR MHealth and UHealth
Patryk Oleszczuk, Michał Kołtowski
The aim of this study was to determine the effect of biochar aging on the content of polycyclic aromatic hydrocarbons (PAHs) (the total content - Ctot , and the freely dissolved - Cfree ) in biochar and its ecotoxicity. Two biochars (BCS and BCM) with varying properties were aged for 420 days at different temperatures (-20 °C, 4 °C, 20 °C, 70 °C), at a variable temperature (-20/20 °C), in the presence of nutrients, and in the presence of inoculum and nutrients. After the aging process, Ctot and Cfree PAHs were determined in samples obtained and an ecotoxicological analysis was performed, which involved tests with bacteria (Vibrio fischeri), invertebrates (Folsomia candida) and plants (Lepidium sativum)...
February 20, 2018: Environmental Pollution
Ulrike Kuchler, Tina Rybaczek, Toni Dobask, Patrick Heimel, Stefan Tangl, Jessica Klehm, Matthias Menzel, Reinhard Gruber
OBJECTIVES: Collagen membranes are not limited to be occlusive barriers as they actively support bone regeneration. However, the impact of bone-derived growth factors on their osteoconductive competence has not been examined. METHODS: Twenty adult Sprague Dawley rats were included in the study. Calvaria defects with a diameter of five millimeter were created. The defect was covered with one layer of a collagen membrane previously soaked in conditioned medium of porcine bone chips or in culture medium alone...
February 16, 2018: Clinical Oral Implants Research
Kristine B Walhovd, Anders M Fjell, René Westerhausen, Lars Nyberg, Klaus P Ebmeier, Ulman Lindenberger, David Bartrés-Faz, William F C Baaré, Hartwig R Siebner, Richard Henson, Christian A Drevon, Gun Peggy Strømstad Knudsen, Isabelle Budin Ljøsne, Brenda W J H Penninx, Paolo Ghisletta, Ole Rogeberg, Lorraine Tyler, Lars Bertram
The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total...
February 12, 2018: European Psychiatry: the Journal of the Association of European Psychiatrists
Wen-Tao Deng, Jie Li, Ping Zhu, Vince A Chiodo, W Clay Smith, Beau Freedman, Wolfgang Baehr, Jijing Pang, William W Hauswirth
Purpose: Blue cone monochromacy (BCM) is an X-linked congenital vision disorder characterized by complete loss or severely reduced L- and M-cone function. Patients with BCM display poor visual acuity, severely impaired color discrimination, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. Recent studies of patients with BCM with adaptive optics scanning laser ophthalmoscopy (AOSLO) showed that they have a disrupted cone mosaic with reduced numbers of cones in the fovea that is normally dominated by L- and M-cones...
2018: Molecular Vision
Babak Hatami Kia, João Rui Galvão Mendes, Heinz-Dieter Müller, Patrick Heimel, Reinhard Gruber
Bones with different embryological origin and mode of ossification are supposed to vary in their capacity for supporting graft consolidation. The aim of the current pilot study was to assess the TGF-β1 activity of bone chips obtained from distinct anatomic locations. Conditioned medium was prepared from bone chips harvested from pig calvaria, mandible, and tibia. Human oral fibroblasts were exposed to bone-conditioned medium (BCM) followed by reverse transcriptase polymerase chain reaction of the TGF-β1 target genes...
January 19, 2018: Journal of Craniofacial Surgery
Jason Bini, Mika Naganawa, Nabeel B Nabulsi, Yiyun Henry Huang, Jim Ropchan, Keunpoong Lim, Soheila Najafzadeh, Kevan C Herold, Gary W Cline, Richard E Carson
Type 1 diabetes mellitus (T1DM) is characterized by a loss of beta cells in the islets of Langerhans of the pancreas and subsequent deficient insulin secretion in response to hyperglycemia. Development of an in vivo test to measure β-cell mass (BCM) would greatly enhance the ability to track diabetes therapies. β-cells and neurological tissues have common cellular receptors and transporters, therefore, we screened brain radioligands for their ability to identify β-cells. Methods: We examined a β-cell gene atlas for endocrine pancreas receptor targets and cross-referenced these targets with brain radioligands that were available at our institution...
January 25, 2018: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
Pablo Molina, Belén Vizcaíno, Mariola D Molina, Sandra Beltrán, Mercedes González-Moya, Antonio Mora, Cristina Castro-Alonso, Julia Kanter, Ana I Ávila, José L Górriz, Nuria Estañ, Luis M Pallardó, Denis Fouque, Juan J Carrero
Background: Compared with conventional haemodialysis (HD), online haemodiafiltration (OL-HDF) achieves a more efficient removal of uraemic toxins and reduces inflammation, which could favourably affect nutritional status. We evaluate the effect of OL-HDF on body composition and nutritional status in prevalent high-flux HD (HF-HD) patients. Methods: In all, 33 adults with chronic kidney disease (CKD) Stage 5 undergoing maintenance HF-HD were assigned to post-dilution OL-HDF (n = 17) or to remain on HF-HD (n = 16, control group) for 12 months...
January 22, 2018: Nephrology, Dialysis, Transplantation
L V Visseaux, A D Durlach, S B Barete, M B B Beylot-Barry, N B Bonnet, A F C Chassine, N F Franck, G H Herve, C L Leclec'h, L M Machet, S I O Ingen-Housz-Oro, T P Petrella, B V Vergier, N O Ortonne, F G Grange
BACKGROUND: A distinctive eruption referred to as "insect bite-like reaction", or "eosinophilic dermatosis of hematologic malignancy" has been described during the course of hematological B-cell malignancies (BCM). However, its clinical evolution, histopathological features and pathogenesis remain unclear. OBJECTIVES: To characterize this eruption and to investigate its pathogenesis and relationship with the underlying BCM. METHODS: In this multicenter retrospective study of the French Study Group on Cutaneous Lymphomas, 37 patients with a BCM and a cutaneous eruption consisting in chronic and/or recurrent papules, papulo-vesicles and/or nodules were included...
January 22, 2018: Journal of the European Academy of Dermatology and Venereology: JEADV
A Köhler, R King, M Bahls, S Groß, A Steveling, S Gärtner, S Schipf, S Gläser, H Völzke, S B Felix, M R P Markus, M Dörr
Peak oxygen uptake (VO2peak) is commonly indexed by total body weight (TBW) to determine cardiopulmonary fitness (CPF). This approach may lead to misinterpretation, particularly in obese subjects. We investigated the normalization of VO2peak by different body composition markers. We analyzed combined data of 3848 subjects (1914 women; 49.7%), aged 20-90, from two independent cohorts of the population-based Study of Health in Pomerania (SHIP-2 and SHIP-TREND). VO2peak was assessed by cardiopulmonary exercise testing...
January 18, 2018: Scandinavian Journal of Medicine & Science in Sports
Charles Vlek
Recently, growing earthquake activity in the northeastern Netherlands has aroused considerable concern among the 600,000 provincial inhabitants. There, at 3 km deep, the rich Groningen gas field extends over 900 km2 and still contains about 600 of the original 2,800 billion cubic meters (bcm). Particularly after 2001, earthquakes have increased in number, magnitude (M, on the logarithmic Richter scale), and damage to numerous buildings. The man-made nature of extraction-induced earthquakes challenges static notions of risk, complicates formal risk assessment, and questions familiar conceptions of acceptable risk...
January 16, 2018: Risk Analysis: An Official Publication of the Society for Risk Analysis
A Dell'Isola, M Steultjens
OBJECTIVES: The existence of phenotypes has been hypothesized to explain the large heterogeneity characterizing the knee osteoarthritis. In a previous systematic review of the literature, six main phenotypes were identified: Minimal Joint Disease (MJD), Malaligned Biomechanical (MB), Chronic Pain (CP), Inflammatory (I), Metabolic Syndrome (MS) and Bone and Cartilage Metabolism (BCM). The purpose of this study was to classify a sample of individuals with knee osteoarthritis (KOA) into pre-defined groups characterized by specific variables that can be linked to different disease mechanisms, and compare these phenotypes for demographic and health outcomes...
2018: PloS One
Daniel Dávila-González, Dong Soon Choi, Roberto R Rosato, Sergio Granados-Principal, John G Kuhn, Wen-Feng Li, Wei Qian, Wen Chen, Anthony J Kozielski, Helen H Wong, Bhuvanesh Dave, Jenny C Chang
PURPOSE: Chemoresistance in triple negative breast cancer (TNBC) is associated with the activation of a survival mechanism orchestrated by the endoplasmic reticulum (EnR) stress response and by inducible nitric oxide synthase (iNOS). Our aim was to determine the effects of pharmacological NOS-inhibition on TNBC. EXPERIMENTAL DESIGN: TNBC cell lines, SUM-159PT, MDA-MB-436, and MDA-MB-468, were treated with docetaxel and NOS-inibitor (L-NMMA) for 24, 48 and 72 hours...
January 4, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Graham Scotland, Moira Cruickshank, Elisabet Jacobsen, David Cooper, Cynthia Fraser, Michal Shimonovich, Angharad Marks, Miriam Brazzelli
BACKGROUND: Chronic kidney disease (CKD) is a long-term condition requiring treatment such as conservative management, kidney transplantation or dialysis. To optimise the volume of fluid removed during dialysis (to avoid underhydration or overhydration), people are assigned a 'target weight', which is commonly assessed using clinical methods, such as weight gain between dialysis sessions, pre- and post-dialysis blood pressure and patient-reported symptoms. However, these methods are not precise, and measurement devices based on bioimpedance technology are increasingly used in dialysis centres...
January 2018: Health Technology Assessment: HTA
Ruyue Fan, Xiangning Bai, Shanshan Fu, Yanmei Xu, Hui Sun, Hong Wang, Yanwen Xiong
Shiga toxin-producing Escherichia coli (STEC) are globally important food-borne pathogens. The isolation of non-O157 STEC is a significant public health challenge due to the dramatic diversity of their phenotypes and genotypes. In the present study, 476 non-O157 STEC strains representing 95 different O-serogroups were used to evaluate tellurite resistance and the performance of 12 different chromogenic agars. Of 476 strains, only 108 (22.7%) strains showed the minimal inhibitory concentration (MIC) values for potassium tellurite being higher than 4μg/ml, and 96 (20...
December 17, 2017: International Journal of Food Microbiology
Hiroyuki Kimura, Yu Ogawa, Hiroyuki Fujimoto, Eri Mukai, Hidekazu Kawashima, Kenji Arimitsu, Kentaro Toyoda, Naotaka Fujita, Yusuke Yagi, Keita Hamamatsu, Takaaki Murakami, Atsushi Murakami, Masahiro Ono, Yuji Nakamoto, Kaori Togashi, Nobuya Inagaki, Hideo Saji
β-cell mass (BCM) is known to be decreased in subjects with type-2 diabetes (T2D). Quantitative analysis for BCM would be useful for understanding how T2D progresses and how BCM affects treatment efficacy and for earlier diagnosis of T2D and development of new therapeutic strategies. However, a noninvasive method to measure BCM has not yet been developed. We developed four 18F-labeled exendin(9-39) derivatives for β-cell imaging by PET: [18F]FB9-Ex(9-39), [18F]FB12-Ex(9-39), [18F]FB27-Ex(9-39), and [18F]FB40-Ex(9-39)...
December 5, 2017: Bioorganic & Medicinal Chemistry
Lieke Joosten, Maarten Brom, Hanneke Peeters, Sandra Heskamp, Martin Béhé, Otto Boerman, Martin Gotthardt
Glucagon-like peptide-1 receptor (GLP-1R) targeting using radiolabeled exendin is a promising approach to noninvasively visualize and determine beta cell mass (BCM), which could help to unravel the pathophysiology of diabetes. However, saturation of the GLP-1R on beta cells occurs at low peptide doses, since the number of receptors expressed under physiological conditions is low. Therefore, tracers with high specific activities are required to sensitively image small variations in BCM. Here, we describe a novel exendin-3-based radiotracer with multiple chelators and determine its potential for in vivo beta cell imaging...
February 5, 2018: Molecular Pharmaceutics
Song Meng, Wei Han, Juan Zhao, Xiao-Hong Jian, Hai-Xue Pan, Gong-Li Tang
As a commercial antibiotic, bicyclomycin (BCM) is currently the only known natural product targeting the transcription termination factor rho. It belongs to a family of highly functionalized diketopiperazine (DKP) alkaloids and bears a unique O-bridged bicyclo[4.2.2]piperazinedione ring system, a C1 triol, and terminal exo-methylene groups. We have identified and characterized the BCM biosynthetic pathway by heterologous biotransformations, in vitro biochemical assays, and one-pot enzymatic synthesis. A tRNA-dependent cyclodipeptide synthase guides the heterodimerization of leucine and isoleucine to afford the DKP precursor; subsequently, six redox enzymes, including five α-ketoglutarate/Fe2+ -dependent dioxygenases and one cytochrome P450 monooxygenase, regio- and stereoselectively install four hydroxy groups (primary, secondary, and two tertiary), an exo-methylene moiety, and a medium-sized bridged ring through the functionalization of eight unactivated C-H bonds...
January 15, 2018: Angewandte Chemie
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