The Effects of Serotonin Receptor Antagonists on Contraction and Relaxation Responses Induced by Electrical Stimulation in the Rat Small Intestine

Background: The main source of 5-HT in body is in enterchromafin cells of intestine, different studies mentioned different roles for endogenous 5-HT and receptors involved and it is not clearified the mechanism of action of endogenous 5-HT. Objectives: To study the role of endogenous 5-HT on modulation of contraction and relaxation responses induced by electrical field stimulation (EFS) in different regions of the rat intestine. Materials and Methods: Segments taken from the rat duodenum, jejunum, mid and terminal ileum were vertically mounted, connected to a transducer and exposed to EFS with different frequencies in the absence and presence of various inhibitors of enteric mediators i. e. specific 5-HT receptor antagonists. Results: EFS-induced responses were sensitive to TTX and partly to atropine, indicating a major neuronal involvement and a cholinergic system. Pre-treatment with WAY100635 (a 5-HT1A receptor antagonist) and granisetron up to 10.0 µM, GR113808 (a 5-HT4 receptor antagonist), methysergide and ritanserin up to 1.0 µM, failed to modify responses to EFS inall examined tissues. In the presence of SB258585 1.0 µM (a 5-HT6 receptor antagonist) there was a trend to enhance contraction in the proximal part of the intestine and reduce contraction in the distal part. Pre-treatment with SB269970A 1.0 µM (5-HT7 receptor antagonist) induced a greater contractile response to EFS at 0.4 Hz only in the duodenum. Conclusions: The application of 5-HT1A, 5-HT2, 5-HT3, 5-HT4, 5-HT6 and 5-HT7 receptor antagonists, applied at concentrations lower than 1.0 µM did not modify the EFS-induced contraction and relaxation responses, whichsuggests the unlikely involvement of endogenous 5-HT in mediating responses to EFS in the described test conditions. Keywords: Electric Stimulation Therapy; Serotonin 5-HT1 Receptor Antagonists; Intestine, Smal

Synchronized dynamics of cortical neurons with time-delay feedback

The dynamics of three mutually coupled cortical neurons with time delays in the coupling are explored numerically and analytically. The neurons are coupled in a line, with the middle neuron sending a somewhat stronger projection to the outer neurons than the feedback it receives, to model for instance the relay of a signal from primary to higher cortical areas. For a given coupling architecture, the delays introduce correlations in the time series at the time-scale of the delay. It was found that the middle neuron leads the outer ones by the delay time, while the outer neurons are synchronized with zero lag times. Synchronization is found to be highly dependent on the synaptic time constant, with faster synapses increasing both the degree of synchronization and the firing rate. Analysis shows that presynaptic input during the interspike interval stabilizes the synchronous state, even for arbitrarily weak coupling, and independent of the initial phase. The finding may be of significance to synchronization of large groups of cells in the cortex that are spatially distanced from each other.Comment: 21 pages, 11 figure

Driven coherent oscillations of a single electron spin in a quantum dot

The ability to control the quantum state of a single electron spin in a quantum dot is at the heart of recent developments towards a scalable spin-based quantum computer. In combination with the recently demonstrated exchange gate between two neighbouring spins, driven coherent single spin rotations would permit universal quantum operations. Here, we report the experimental realization of single electron spin rotations in a double quantum dot. First, we apply a continuous-wave oscillating magnetic field, generated on-chip, and observe electron spin resonance in spin-dependent transport measurements through the two dots. Next, we coherently control the quantum state of the electron spin by applying short bursts of the oscillating magnetic field and observe about eight oscillations of the spin state (so-called Rabi oscillations) during a microsecond burst. These results demonstrate the feasibility of operating single-electron spins in a quantum dot as quantum bits.Comment: Total 25 pages. 11 pages main text, 5 figures, 9 pages supplementary materia

Honeybee Colony Vibrational Measurements to Highlight the Brood Cycle

Insect pollination is of great importance to crop production worldwide and honey bees are amongst its chief facilitators. Because of the decline of managed colonies, the use of sensor technology is growing in popularity and it is of interest to develop new methods which can more accurately and less invasively assess honey bee colony status. Our approach is to use accelerometers to measure vibrations in order to provide information on colony activity and development. The accelerometers provide amplitude and frequency information which is recorded every three minutes and analysed for night time only. Vibrational data were validated by comparison to visual inspection data, particularly the brood development. We show a strong correlation between vibrational amplitude data and the brood cycle in the vicinity of the sensor. We have further explored the minimum data that is required, when frequency information is also included, to accurately predict the current point in the brood cycle. Such a technique should enable beekeepers to reduce the frequency with which visual inspections are required, reducing the stress this places on the colony and saving the beekeeper time

Introduction: Examined Live – An Epistemological Exchange Between Philosophy and Cultural Psychology on Reflection

Besides the general agreement about the human capability of reflection, there is a large area of disagreement and debate about the nature and value of “reflective scrutiny” and the role of “second-order states” in everyday life. This problem has been discussed in a vast and heterogeneous literature about topics such as epistemic injustice, epistemic norms, agency, understanding, meta-cognition etc. However, there is not yet any extensive and interdisciplinary work, specifically focused on the topic of the epistemic value of reflection. This volume is one of the first attempts aimed at providing an innovative contribution, an exchange between philosophy, epistemology and psychology about the place and value of reflection in everyday life. Our goal in the next sections is not to offer an exhaustive overview of recent work on epistemic reflection, nor to mimic all of the contributions made by the chapters in this volume. We will try to highlight some topics that have motivated a new resumption of this field and, with that, drawing on chapters from this volume where relevant. Two elements defined the scope and content of this volume, on the one hand, the crucial contribution of Ernest Sosa, whose works provide original and thought-provoking contributions to contemporary epistemology in setting a new direction for old dilemmas about the nature and value of knowledge, giving a central place to reflection. On the other hand, the recent developments of cultural psychology, in the version of the “Aalborg approach”, reconsider the object and scope of psychological sciences, stressing that “[h]uman conduct is purposeful”

Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage.

Colibactin is an assumed human gut bacterial genotoxin, whose biosynthesis is linked to the clb genomic island that has a widespread distribution in pathogenic and commensal human enterobacteria. Colibactin-producing gut microbes promote colon tumour formation and enhance the progression of colorectal cancer via cellular senescence and death induced by DNA double-strand breaks (DSBs); however, the chemical basis that contributes to the pathogenesis at the molecular level has not been fully characterized. Here, we report the discovery of colibactin-645, a macrocyclic colibactin metabolite that recapitulates the previously assumed genotoxicity and cytotoxicity. Colibactin-645 shows strong DNA DSB activity in vitro and in human cell cultures via a unique copper-mediated oxidative mechanism. We also delineate a complete biosynthetic model for colibactin-645, which highlights a unique fate of the aminomalonate-building monomer in forming the C-terminal 5-hydroxy-4-oxazolecarboxylic acid moiety through the activities of both the polyketide synthase ClbO and the amidase ClbL. This work thus provides a molecular basis for colibactin's DNA DSB activity and facilitates further mechanistic study of colibactin-related colorectal cancer incidence and prevention

Latest Results from the Heidelberg-Moscow Double Beta Decay Experiment

New results for the double beta decay of 76Ge are presented. They are extracted from Data obtained with the HEIDELBERG-MOSCOW, which operates five enriched 76Ge detectors in an extreme low-level environment in the GRAN SASSO. The two neutrino accompanied double beta decay is evaluated for the first time for all five detectors with a statistical significance of 47.7 kg y resulting in a half life of (T_(1/2))^(2nu) = [1.55 +- 0.01 (stat) (+0.19) (-0.15) (syst)] x 10^(21) years. The lower limit on the half-life of the 0nu beta-beta decay obtained with pulse shape analysis is (T_(1/2))^(0_nu) > 1.9 x 10^(25) [3.1 x 10^(25)] years with 90% C.L. (68% C.L.) (with 35.5 kg y). This results in an upper limit of the effective Majorana neutrino mass of 0.35 eV (0.27 eV). No evidence for a Majoron emitting decay mode or for the neutrinoless mode is observed.Comment: 14 pages, revtex, 6 figures, Talk was presented at third International Conference ' Dark Matter in Astro and Particle Physics' - DARK2000, to be publ. in Proc. of DARK2000, Springer (2000). Please look into our HEIDELBERG Non-Accelerator Particle Physics group home page: http://www.mpi-hd.mpg.de/non_acc

Evolution of the Antiretroviral Restriction Factor TRIMCyp in Old World Primates

The retroviral restriction factor TRIMCyp, which is a fusion protein derived from the TRIM5 gene, blocks replication at a post-entry step. Among Old World primates, TRIMCyp has been found in four species of Asian macaques, but not in African monkeys. To further define the evolutionary origin of Old World TRIMCyp, we examined two species of baboons (genus Papio) and three additional macaque species, including M. sylvanus, which is the only macaque species found outside Asia, and represents the earliest diverging branch of the macaque lineage. None of four P. cynocephalus anubis, one P. hamadryas, and 36 M. sylvanus had either TRIMCyp mRNA or the genetic features required for its expression. M. sylvanus genomic sequences indicated that the lack of TRIMCyp in this species was not due to genetic homogeneity among specimens studied and revealed the existence of four TRIM5α alleles, all distinct from M. mulatta and Papio counterparts. Together with existing data on macaque evolution, our findings indicate that TRIMCyp evolved in the ancestors of Asian macaques approximately 5–6 million years before present (ybp), likely as a result of a retroviral threat. TRIMCyp then became fixed in the M. nemestrina lineage after it diverged from M. nigra, approximately 2 million ybp. The macaque lineage is unique among primates studied so far due to the presence and diversity of both TRIM5 and TRIMCyp restriction factors. Studies of these antiviral proteins may provide valuable information about natural antiviral mechanisms, and give further insight into the factors that shaped the evolution of macaque species

Extracellular vesicles in diagnostics and therapy of the ischaemic heart: Position Paper from the Working Group on Cellular Biology of the Heart of the European Society of Cardiology

Extracellular vesicles (EVs)-particularly exosomes and microvesicles (MVs)-are attracting considerable interest in the cardiovascular field as the wide range of their functions is recognized. These capabilities include transporting regulatory molecules including different RNA species, lipids, and proteins through the extracellular space including blood and delivering these cargos to recipient cells to modify cellular activity. EVs powerfully stimulate angiogenesis, and can protect the heart against myocardial infarction. They also appear to mediate some of the paracrine effects of cells, and have therefore been proposed as a potential alternative to cell-based regenerative therapies. Moreover, EVs of different sources may be useful biomarkers of cardiovascular disease identities. However, the methods used for the detection and isolation of EVs have several limitations and vary widely between studies, leading to uncertainties regarding the exact population of EVs studied and how to interpret the data. The number of publications in the exosome and MV field has been increasing exponentially in recent years and, therefore, in this ESC Working Group Position Paper, the overall objective is to provide a set of recommendations for the analysis and translational application of EVs focussing on the diagnosis and therapy of the ischaemic heart. This should help to ensure that the data from emerging studies are robust and repeatable, and optimize the pathway towards the diagnostic and therapeutic use of EVs in clinical studies for patient benefit