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51.
52.
Gaseous neurotransmitters such as nitric oxide (NO) provide a unique and often overlooked mechanism for neurons to communicate through diffusion within a network, independent of synaptic connectivity. NO provides homeostatic control of intrinsic excitability. Here we conduct a theoretical investigation of the distinguishing roles of NO-mediated diffusive homeostasis in comparison with canonical non-diffusive homeostasis in cortical networks. We find that both forms of homeostasis provide a robust mechanism for maintaining stable activity following perturbations. However, the resulting networks differ, with diffusive homeostasis maintaining substantial heterogeneity in activity levels of individual neurons, a feature disrupted in networks with non-diffusive homeostasis. This results in networks capable of representing input heterogeneity, and linearly responding over a broader range of inputs than those undergoing non-diffusive homeostasis. We further show that these properties are preserved when homeostatic and Hebbian plasticity are combined. These results suggest a mechanism for dynamically maintaining neural heterogeneity, and expose computational advantages of non-local homeostatic processes. 相似文献
53.
Arabidopsis RETINOBLASTOMA-RELATED Is Required for Stem Cell Maintenance, Cell Differentiation, and Lateral Organ Production 总被引:1,自引:0,他引:1
Lorenzo Borghi Ruben Gutzat Johannes F��tterer Yec'han Laizet Lars Hennig Wilhelm Gruissem 《The Plant cell》2010,22(6):1792-1811
Several genes involved in the regulation of postembryonic organ initiation and growth have been identified. However, it remains largely unclear how developmental cues connect to the cell cycle. RETINOBLASTOMA RELATED (RBR) is a plant homolog of the tumor suppressor Retinoblastoma (pRb), which is a key regulator of the cell cycle. Using inducible RNA interference (RNAi) against Arabidopsis thaliana
RBR (RBRi), we reduced RBR expression levels at different stages of plant development. Conditional reduction or loss of RBR function disrupted cell division patterns, promoted context-dependent cell proliferation, and negatively influenced establishment of cell differentiation. Several lineages of toti- and pluripotent cells, including shoot apical meristem stem cells, meristemoid mother cells, and procambial cells, failed to produce appropriately differentiated cells. Meristem activity was altered, leading to a disruption of the CLAVATA-WUSCHEL feedback loop and inhibition of lateral organ formation. Release of RBR from RNAi downregulation restored meristem activity. Gene profiling analyses soon after RBRi induction revealed that a change in RBR homeostasis is perceived as a stress, even before genes regulated by RBR-E2F become deregulated. The results establish RBR as a key cell cycle regulator required for coordination of cell division, differentiation, and cell homeostasis. 相似文献
54.
Doris Freißmuth Alexander Hiltgartner Christiane Stahl‐Hennig Dietmar Fuchs Klara Tenner‐Racz Paul Racz Klaus Überla Alexander Strasak Manfred P. Dierich Heribert Stoiber Barbara Falkensammer 《Journal of medical primatology》2010,39(2):97-111
Background To determine the correlation between protection and humoral immune response against simian immunodeficiency virus (SIVmac251), 11 macaques were immunized with live‐attenuated SIVmac239Δnef either intravenously or via the tonsils and exposed to SIVmac251 after either 6 or 15 months along with unvaccinated controls. Results Independent of the route of vaccine application, viremia was significantly reduced in vaccinees compared with controls 2 weeks post‐challenge. Concomitantly, viremia correlated inversely with SIV‐specific IgG, complement‐mediated lysis and neutralizing antibodies and these parameters seemed to contribute to reduced viremia. During chronic infection, six monkeys controlled viremia in the circulation (two or fewer infectious units per 106 PBMCs) and showed no signs of trapping in lymphatic tissues (Appendix S1). Conclusions As no significant differences were observed throughout the study, with respect to the humoral immune response and viremia control, between the two vaccinated cohorts, mucosal immunization strategies are recommended due to more simplified application. 相似文献
55.
C. Leinert C. Stahl‐Hennig A. Ecker T. Schneider D. Fuchs U. Sauermann S. Sopper 《Journal of medical primatology》2010,39(4):243-251
Background Chronic immune activation is a hallmark of HIV infection and has been postulated as major factor in the pathogenesis of AIDS. Recent evidence suggests that activation of immune cells is triggered by microbial translocation through the impaired gastrointestinal barrier. Methods To determine the association between microbial translocation and disease progression, we have retrospectively analyzed microbial products, viral load and markers of immune activation in a cohort of 37 simian immunodeficiency virus‐infected rhesus monkeys, divided in two groups with distinct disease courses. Results As seen in HIV‐infected patients, we found elevated levels of lipopolysaccharide (LPS) in infected animals. However, LPS levels or LPS control mechanisms like endotoxin core antibodies or LPS‐binding protein did not differ between groups with different disease progression. In contrast, neopterin, a metabolic product of activated macrophages, was higher in fast progressors than in slow progressors. Conclusion Our data indicate that translocation of microbial products is not the major driving force of immune activation in HIV infection. 相似文献
56.
Ruhaak LR Hennig R Huhn C Borowiak M Dolhain RJ Deelder AM Rapp E Wuhrer M 《Journal of proteome research》2010,9(12):6655-6664
High-throughput methods for oligosaccharide analysis are required when searching for glycan-based biomarkers. Next to mass spectrometry-based methods, which allow fast and reproducible analysis of such compounds, further separation-based techniques are needed, which allow for quantitative analysis. Here, an optimized sample preparation method for N-glycan-profiling by multiplexed capillary gel electrophoresis with laser-induced fluorescence detection (CGE-LIF) was developed, enabling high-throughput glycosylation analysis. First, glycans are released enzymatically from denatured plasma glycoproteins. Second, glycans are labeled with APTS using 2-picoline borane as a nontoxic and efficient reducing agent. Reaction conditions are optimized for a high labeling efficiency, short handling times, and only limited loss of sialic acids. Third, samples are subjected to hydrophilic interaction chromatography (HILIC) purification at the 96-well plate format. Subsequently, purified APTS-labeled N-glycans are analyzed by CGE-LIF using a 48-capillary DNA sequencer. The method was found to be robust and suitable for high-throughput glycan analysis. Even though the method comprises two overnight incubations, 96 samples can be analyzed with an overall labor allocation time of 2.5 h. The method was applied to serum samples from a pregnant woman, which were sampled during first, second, and third trimesters of pregnancy, as well as 6 weeks, 3 months, and 6 months postpartum. Alterations in the glycosylation patterns were observed with gestation and time after delivery. 相似文献
57.
Stefan Telser Martin Staudacher Bernhard Hennig Yvonne Ploner Anton Amann Hartmann Hinterhuber Monika Ritsch-Marte 《Journal of biological physics》2007,33(1):19-33
The correlation behavior in the heart beat rate significantly differs with respect to light sleep, deep sleep, and REM sleep.
We investigate whether fluctuations of the heart beat rhythm may serve as a surrogate parameter for rapidly changing sleep
phenomena, and if these changes are accessible by progressive beat-by-beat analysis of the sleep electrocardiogram (ECG). 相似文献
58.
Volkhard Seitz Sigrid Schaper Anja Dr?ge Dido Lenze Michael Hummel Steffen Hennig 《Nucleic acids research》2015,43(20):e135
Two-step PCR procedures are an efficient and well established way to generate amplicon libraries for NGS sequencing. However, there is a high risk of cross-contamination by carry-over of amplicons from first to second amplification rounds, potentially leading to severe misinterpretation of results. Here we describe a new method able to prevent and/or to identify carry-over contaminations by introducing the K-box, a series of three synergistically acting short sequence elements. Our K-boxes are composed of (i) K1 sequences for suppression of contaminations, (ii) K2 sequences for detection of possible residual contaminations and (iii) S sequences acting as separators to avoid amplification bias. In order to demonstrate the effectiveness of our method we analyzed two-step PCR NGS libraries derived from a multiplex PCR system for detection of T-cell receptor beta gene rearrangements. We used this system since it is of high clinical relevance and may be affected by very low amounts of contaminations. Spike-in contaminations are effectively blocked by the K-box even at high rates as demonstrated by ultra-deep sequencing of the amplicons. Thus, we recommend implementation of the K-box in two-step PCR-based NGS systems for research and diagnostic applications demanding high sensitivity and accuracy. 相似文献
59.
O. Assemat M. Antoine J.-M. Fourquez M. Wierzbicki Y. Charton P. Hennig F. Perron-Sierra G. Ferry J.A. Boutin M.-A. Delsuc 《Analytical biochemistry》2015
Human hexokinase enzyme IV (EC 2.7.1.1) catalyzes the phosphorylation of glucose and regulates the level of glucose. This enzyme exhibits strong positive cooperativity due to an allosteric transition between an inactive form and a closed active form. This form can be stabilized by activators and, thus, can increase its turnover by a kinetic memory effect characterized by a slow decay to the inactive state. The structural details of this kinetic allostery are known. Several synthetic activators have been reported. We present a preliminary nuclear magnetic resonance (NMR) screening of a chemical library in search of molecules with some affinity for glucokinase (GK). The library, composed of eight molecules with known activity as well as molecules that display no interaction, has been tested using the FAXS (fluorine chemical shift anisotropy and exchange for screening) method, based on monitoring the R2 relaxation of the 19F spin. To ensure a valid interaction measurement, the enzyme was placed in the presence of glucose and magnesium. The binding signal of one known fluorinated ligand was measured by determining the displacement of the known ligand. This simple measure of the 19F signal intensity after an 80-ms spin echo correlates nicely with the EC50, opening a route for NMR screening of GK activators. 相似文献
60.
Offset responses upon termination of a stimulus are crucial for perceptual grouping and gap detection. These gaps are key features of vocal communication, but an ionic mechanism capable of generating fast offsets from auditory stimuli has proven elusive. Offset firing arises in the brainstem superior paraolivary nucleus (SPN), which receives powerful inhibition during sound and converts this into precise action potential (AP) firing upon sound termination. Whole-cell patch recording in?vitro showed that offset firing was triggered by IPSPs rather than EPSPs. We show that AP firing can emerge from inhibition through integration of large IPSPs, driven by an extremely negative chloride reversal potential (E(Cl)), combined with a large hyperpolarization-activated nonspecific cationic current (I(H)), with a secondary contribution from a T-type calcium conductance (I(TCa)). On activation by the IPSP, I(H) potently accelerates the membrane time constant, so when the sound ceases, a rapid repolarization triggers multiple offset APs that match onset timing accuracy. 相似文献