2,769 research outputs found
Insulin-like growth factor I is an independent coregulatory modulator of natural killer (NK) cell activity.
We aimed to investigate the natural killer (NK) cell activity in
hGH-deficient adults and to analyze the effect of insulin-like growth
factor (IGF)-I in uivo and in vitro on NK cell activity. NK cell activity
was measured in a 4-h nonisotopic assay with europium-labeled and
cryopreserved K-562 cells. NK-cell numbers were measured after
incubation with murine monoclonal CD3 and CD16 antibodies by flow
cytometry analysis. In a cross-sectional study, the basal and interferon-
p (IFN-P) stimulated (1000 IU/ml) NK cell activity of 15 hGHdeficient
patients and 15 age- and sex-matched controls was measured.
The percentages and absolute numbers of CD3./16+ NK-cells
were not significantly different in the patient vs. control group. The
basal and IFN-P stimulated NK cell activity however was significantly
decreased in the patient vs. control group at all effecter/target
(E/T) cell ratios from 12.5-100 (e.g. 17 ? 3 vs. 28 ? 3% lysis without
IFN-P, P < 0.05, and 42 t 4 vs. 57 2 4% lysis with IFN-0, P < 0.05;
both at E/T 50). IGF-I levels of patients and controls showed a significant
positive correlation with NK cell activity (r = 0.37; P < 0.05).
In an IGF-I in vitro study (IGF-I in vitro 250-1250 kg/L), the basal and
IFN-P stimulated NK cell activity of 13 hGH-deficient patients and of
18 normal subjects was significantly enhanced by IGF-I in vitro (e.g.
GH-deficient patients: 9 ? 2 us. 10 2 2% lysis without IFN-P, P < 0.05
and 25 + 4 vs. 30 + 4% lysis with IFN-/3, P < 0.005; and normal
subjects: 15 + 3 vs. 23 ? 3% lysis without IFN-/3, P < 0.001 and 35 2
4 us. 44 + 5% lysis with IFN-P, P < 0.001; both at IGF-I 500 pg/L).
In summary, in our cross-sectional study, adult GH-deficient patients
showed a significantly lower basal and IFN-P stimulated NK cell
activity than matched controls, despite equal NK cell numbers. IGF-I
levels of patients and controls showed a weak positive correlation with
NK cell activity. In an in vitro study, IGF-I significantly enhanced
basal and IFN-P stimulated NK cell activity of hGH-deficient patients
and also of normal subjects. The decreased NK cell activity in GHdeficient
patients may be caused at least in part by low serum IGF-I
levels. IGF-I appears to be an independent coregulatory modulator of
NK cell activity. (Endocrinology 137: 5332-5336, 1996
FROM DROPPING BOMBS TO BLASTING BITS: ENVISIONING TACTICAL OPERATIONS IN THE INFORMATION ENVIRONMENT BY EMULATING THE EVOLUTION OF AIR-GROUND INTEGRATION
A gap exists in the United States military at the tactical level in organization, capabilities, and authorities to conduct operations in the information environment (OIE). This thesis identifies a potential solution by analyzing and applying lessons learned from air-ground integration: a dimension of warfare that was once a novel concept comparable to modern information, cyber, and space. Air-ground integration evolved from strategic reconnaissance in World War I to modern attack helicopters, hand-launched killer drones, and tactical joint terminal attack controllers (JTACs). Today, JTACs provide the ground commander with an air-ground integration expert at the tactical edge, equipped with lethal and nonlethal capabilities, and who falls under authorities that vary by location and type of operation. The JTAC qualification is recognized across the joint force and NATO and minimizes the number of pilots needed at ground units. This thesis argues that creating an information, cyber, and space equivalent to the JTAC could enable the joint force to more effectively conduct tactical OIE. This multi-domain terminal effects controller (MDTEC) would be jointly certified, qualified, and designated to advise ground commanders on the information environment, employ tactical information tools, and leverage joint information, cyber, and space assets to create effects.Master Sergeant, United States Marine CorpsApproved for public release. Distribution is unlimited
G protein-coupled receptor kinase-2 (GRK-2) regulates serotonin metabolism through the monoamine oxidase AMX-2 in Caenorhabditis elegans.
G protein-coupled receptors (GPCRs) regulate many animal behaviors. GPCR signaling is mediated by agonist-promoted interactions of GPCRs with heterotrimeric G proteins, GPCR kinases (GRKs), and arrestins. To further elucidate the role of GRKs in regulating GPCR-mediated behaviors, we utilized the genetic model system Caenorhabditis elegans Our studies demonstrate that grk-2 loss-of-function strains are egg laying-defective and contain low levels of serotonin (5-HT) and high levels of the 5-HT metabolite 5-hydroxyindole acetic acid (5-HIAA). The egg laying defect could be rescued by the expression of wild type but not by catalytically inactive grk-2 or by the selective expression of grk-2 in hermaphrodite-specific neurons. The addition of 5-HT or inhibition of 5-HT metabolism also rescued the egg laying defect. Furthermore, we demonstrate that AMX-2 is the primary monoamine oxidase that metabolizes 5-HT in C. elegans, and we also found that grk-2 loss-of-function strains have abnormally high levels of AMX-2 compared with wild-type nematodes. Interestingly, GRK-2 was also found to interact with and promote the phosphorylation of AMX-2. Additional studies reveal that 5-HIAA functions to inhibit egg laying in a manner dependent on the 5-HT receptor SER-1 and the G protein GOA-1. These results demonstrate that GRK-2 modulates 5-HT metabolism by regulating AMX-2 function and that 5-HIAA may function in the SER-1 signaling pathway
HRSC Mapping Database: A New Tool to Collect and View Available HRSC-Based Geological Maps Worldwide
We present a new online database for quick and easy access to already published HRSC-based geological mappings on Mars
Antiferromagnetic Ising spin glass competing with BCS pairing interaction in a transverse field
The competition among spin glass (SG), antiferromagnetism (AF) and local
pairing superconductivity (PAIR) is studied in a two-sublattice fermionic Ising
spin glass model with a local BCS pairing interaction in the presence of an
applied magnetic transverse field . In the present approach, spins in
different sublattices interact with a Gaussian random coupling with an
antiferromagnetic mean and standard deviation . The problem is
formulated in the path integral formalism in which spin operators are
represented by bilinear combinations of Grassmann variables. The saddle-point
Grand Canonical potential is obtained within the static approximation and the
replica symmetric ansatz. The results are analysed in phase diagrams in which
the AF and the SG phases can occur for small ( is the strength of the
local superconductor coupling written in units of ), while the PAIR phase
appears as unique solution for large . However, there is a complex line
transition separating the PAIR phase from the others. It is second order at
high temperature that ends in a tricritical point. The quantum fluctuations
affect deeply the transition lines and the tricritical point due to the
presence of .Comment: 16 pages, 6 figures, accepted Eur. Phys. J.
Shaping Robot Gestures to Shape Users' Perception: the Effect of Amplitude and Speed on Godspeed Ratings
This work analyses the relationship between the way robots gesture and the way those gestures are perceived by human users. In particular, this work shows how modifying the amplitude and speed of a gesture affect the Godspeed scores given to those gestures, by means of an experiment involving 45 stimuli and 30 observers. The results suggest that shaping gestures aimed at manifesting the inner state of the robot (e.g., cheering or showing disappointment) tends to change the perception of Animacy (the dimension that accounts for how driven by endogenous factors the robot is perceived to be), while shaping gestures aimed at achieving an interaction effect (e.g., engaging and disengaging) tends to change the perception of Anthropomorphism, Likeability and Perceived Safety (the dimensions that account for the social aspects of the perception)
“Care for the common home” : responses to Pope Francis's Encyclical Letter
Abstract: This article aims to build awareness of the growing global crisis in social, economic and environmental terms from different disciplinary approaches. The authors respond to the message of Pope Francis presented in his Encyclical Letter published in 2015. The article provides a short current overview of the discourse and presents three hypotheses anchored in the disciplines of Psychology, Health and Theology for a deeper discussion of Pope Francis’s viewpoints on the challenges to humankind and how to address them. It thereby contributes to the discourse on health and religion with regard to the Pope’s message to the world community. The article leads to an interdisciplinary conclusion and directions for future research and practice
Tetraspanin (TSP-17) Protects Dopaminergic Neurons against 6-OHDA-Induced Neurodegeneration in <i>C. elegans</i>
Parkinson's disease (PD), the second most prevalent neurodegenerative disease after Alzheimer's disease, is linked to the gradual loss of dopaminergic neurons in the substantia nigra. Disease loci causing hereditary forms of PD are known, but most cases are attributable to a combination of genetic and environmental risk factors. Increased incidence of PD is associated with rural living and pesticide exposure, and dopaminergic neurodegeneration can be triggered by neurotoxins such as 6-hydroxydopamine (6-OHDA). In C. elegans, this drug is taken up by the presynaptic dopamine reuptake transporter (DAT-1) and causes selective death of the eight dopaminergic neurons of the adult hermaphrodite. Using a forward genetic approach to find genes that protect against 6-OHDA-mediated neurodegeneration, we identified tsp-17, which encodes a member of the tetraspanin family of membrane proteins. We show that TSP-17 is expressed in dopaminergic neurons and provide genetic, pharmacological and biochemical evidence that it inhibits DAT-1, thus leading to increased 6-OHDA uptake in tsp-17 loss-of-function mutants. TSP-17 also protects against toxicity conferred by excessive intracellular dopamine. We provide genetic and biochemical evidence that TSP-17 acts partly via the DOP-2 dopamine receptor to negatively regulate DAT-1. tsp-17 mutants also have subtle behavioral phenotypes, some of which are conferred by aberrant dopamine signaling. Incubating mutant worms in liquid medium leads to swimming-induced paralysis. In the L1 larval stage, this phenotype is linked to lethality and cannot be rescued by a dop-3 null mutant. In contrast, mild paralysis occurring in the L4 larval stage is suppressed by dop-3, suggesting defects in dopaminergic signaling. In summary, we show that TSP-17 protects against neurodegeneration and has a role in modulating behaviors linked to dopamine signaling
Influence of pump laser fluence on ultrafast structural changes in myoglobin
High-intensity femtosecond pulses from an X-ray free-electron laser enable pump probe experiments for investigating electronic and nuclear changes during light-induced reactions. On time scales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer. However, all ultra-fast TR-SFX studies to date have employed such high pump laser energies that several photons were nominally absorbed per chromophore. As multiphoton absorption may force the protein response into nonphysiological pathways, it is of great concern whether this experimental approach allows valid inferences to be drawn vis-a-vis biologically relevant single-photon-induced reactions. Here we describe ultrafast pump-probe SFX experiments on photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe-CO bond distance (predicted by recent quantum wavepacket dynamics) are seen to depend strongly on pump laser energy. Our results confirm both the feasibility and necessity of performing TR-SFX pump probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing design and interpretation of ultrafast TR-SFX pump probe experiments such that biologically relevant insight emerges
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