12 research outputs found
Impact of the Variable Killer Ig-Like ReceptorāHuman Leukocyte Antigen Interactions on Natural Killer Cell Cytotoxicity Toward Foreign CD4 T Cells
Impact of the variable killer Ig-like receptor-human leukocyte antigen interactions on natural killer cell cytotoxicity toward foreign CD4 T cells
Citizen science in the classroom. Guidelines for organisers of citizen science projects.
Met deze gids willen we aanbieders van citizenscienceinitiatieven laten kennismaken met de opportuniteiten en eventuele struikelblokken bij de implementatie van hun project in het Vlaamse onderwijs. We starten met een omschrijving van het begrip ācitizen scienceā en de voordelen ervan voor wetenschap en onderwijs. Je maakt in deze gids kennis met de structuur van het Vlaamse onderwijslandschap, van ministerie tot individuele leerkracht. Daarnaast geven we je tips om onderzoeksactiviteiten naar de klascontext te brengen. We maken ook enkele praktische overwegingen over citizen science met het onderwijs. Zo bespreken we bijvoorbeeld hoe je leerkrachten en leerlingen kunt motiveren en welke stappen je best neemt op vlak van data- en privacybeleid bij minderjarige burgerwetenschappers. Doorheen de gids verwijzen we naar inspirerende binnenlandse en internationale voorbeelden van citizen science in de klas. We brengen samenvattingen en doorverwijslinks van deze voorbeelden samen in een overzicht. De onderwijswereld heeft ten slotte haar eigen jargon. We verklaren belangrijke termen in het lexicon
Citizen science in de klas. Een gids voor initiatiefnemers van citizen-scienceprojecten
Met deze gids willen we aanbieders van citizenscienceinitiatieven laten kennismaken met de opportuniteiten en eventuele struikelblokken bij de implementatie van hun project in het Vlaamse onderwijs. We starten met een omschrijving van het begrip ācitizen scienceā en de voordelen ervan voor wetenschap en onderwijs. Je maakt in deze gids kennis met de structuur van het Vlaamse onderwijslandschap, van ministerie tot individuele leerkracht. Daarnaast geven we je tips om onderzoeksactiviteiten naar de klascontext te brengen. We maken ook enkele praktische overwegingen over citizen science met het onderwijs. Zo bespreken we bijvoorbeeld hoe je leerkrachten en leerlingen kunt motiveren en welke stappen je best neemt op vlak van data- en privacybeleid bij minderjarige burgerwetenschappers. Doorheen de gids verwijzen we naar inspirerende binnenlandse en internationale voorbeelden van citizen science in de klas. We brengen samenvattingen en doorverwijslinks van deze voorbeelden samen in een overzicht. De onderwijswereld heeft ten slotte haar eigen jargon. We verklaren belangrijke termen in het lexicon
JNJ-40255293, a Novel Adenosine A<sub>2A</sub>/A<sub>1</sub> Antagonist with Efficacy in Preclinical Models of Parkinsonās Disease
Adenosine A<sub>2A</sub> antagonists
are believed to have therapeutic
potential in the treatment of Parkinsonās disease (PD). We
have characterized the dual adenosine A<sub>2A</sub>/A<sub>1</sub> receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)Āethoxy]-4-phenyl-5<i>H</i>-indenoĀ[1,2-<i>d</i>]Āpyrimidin-5-one). JNJ-40255293
was a high-affinity (7.5 nM) antagonist at the human A<sub>2A</sub> receptor with 7-fold in vitro selectivity versus the human A<sub>1</sub> receptor. A similar A<sub>2A</sub>:A<sub>1</sub> selectivity
was seen in vivo (ED<sub>50</sub>ās of 0.21 and 2.1 mg/kg p.o.
for occupancy of rat brain A<sub>2A</sub> and A<sub>1</sub> receptors,
respectively). The plasma EC<sub>50</sub> for occupancy of rat brain
A<sub>2A</sub> receptors was 13 ng/mL. In sleepāwake encephalographic
(EEG) studies, JNJ-40255293 dose-dependently enhanced a consolidated
waking associated with a subsequent delayed compensatory sleep (minimum
effective dose: 0.63 mg/kg p.o.). As measured by microdialysis, JNJ-40255293
did not affect dopamine and noradrenaline release in the prefrontal
cortex and the striatum. However, it was able to reverse effects (catalepsy,
hypolocomotion, and conditioned avoidance impairment in rats; hypolocomotion
in mice) produced by the dopamine D<sub>2</sub> antagonist haloperidol.
The compound also potentiated the agitation induced by the dopamine
agonist apomorphine. JNJ-40255293 also reversed hypolocomotion produced
by the dopamine-depleting agent reserpine and potentiated the effects
of l-dihydroxyphenylalanine (L-DOPA) in rats with unilateral
6-hydroxydopamine-induced lesions of the nigro-striatal pathway, an
animal model of Parkinsonās disease. Extrapolating from the
rat receptor occupancy doseāresponse curve, the occupancy required
to produce these various effects in rats was generally in the range
of 60ā90%. The findings support the continued research and
development of A<sub>2A</sub> antagonists as potential treatments
for PD
JNJ-40255293, a novel adenosine A2A/A1 antagonist with efficacy in preclinical models of Parkinson's disease
Adenosine A2A antagonists are believed to have therapeutic potential in the treatment of Parkinsonās disease (PD). We have characterized the dual adenosine A2A/A1 receptor antagonist JNJ-40255293 (2-amino-8-[2-(4-morpholinyl)ethoxy]-4-phenyl-5H-indeno[1,2-d]pyrimidin-5-one). JNJ-40255293 was a high-affinity (7.5 nM) antagonist at the human A2A receptor with 7-fold in vitro selectivity versus the human A1 receptor. A similar A2A:A1 selectivity was seen in vivo (ED50ās of 0.21 and 2.1 mg/kg p.o. for occupancy of rat brain A2A and A1 receptors, respectively). The plasma EC50 for occupancy of rat brain A2A receptors was 13 ng/mL. In sleepāwake encephalographic (EEG) studies, JNJ-40255293 dose-dependently enhanced a consolidated waking associated with a subsequent delayed compensatory sleep (minimum effective dose: 0.63 mg/kg p.o.). As measured by microdialysis, JNJ-40255293 did not affect dopamine and noradrenaline release in the prefrontal cortex and the striatum. However, it was able to reverse effects (catalepsy, hypolocomotion, and conditioned avoidance impairment in rats; hypolocomotion in mice) produced by the dopamine D2 antagonist haloperidol. The compound also potentiated the agitation induced by the dopamine agonist apomorphine. JNJ-40255293 also reversed hypolocomotion produced by the dopamine-depleting agent reserpine and potentiated the effects of l-dihydroxyphenylalanine (L-DOPA) in rats with unilateral 6-hydroxydopamine-induced lesions of the nigro-striatal pathway, an animal model of Parkinsonās disease. Extrapolating from the rat receptor occupancy doseāresponse curve, the occupancy required to produce these various effects in rats was generally in the range of 60ā90%. The findings support the continued research and development of A2A antagonists as potential treatments for PD
The role of NK cells in HIV-1 protection : autologous, allogeneic or both?
Natural killer (NK) cells specialize in killing virally infected- or tumor cells and are part of the innate immune system. The activational state of NK cells is determined by the balance of incoming activating and inhibitory signals mediated by receptor-ligand binding with the target cell. These receptor-ligand bonds mainly consist of the killer immunoglobulin-like receptors (KIR), which are expressed at the cell surface of NK cells, and their ligands: the highly variable human leukocyte antigen -class I molecules (HLA). Absence of an inhibitory receptor-ligand bond lowers the NK cell activation threshold, whereas an activating receptor-ligand bond stimulates the cell, potentially overcoming this threshold and triggering NK cell activation. NK cells influence the course of infection as well as the acquisition of HIV-1. Several lines of evidence relate the activating NK cell receptor KIR3DS1, in the presence or absence of its putative ligand HLA-Bw4, with slower disease progression as well as resistance to HIV-1 infection. Overall, resistance to HIV-1 infection predominantly correlates with activating KIR/HLA profiles, consisting of e.g. activating KIRs, group B haplotypes, or inhibitory KIRs in absence of their ligands. Such a conclusion is less evident for studies of HIV-1 disease progression, with studies reporting beneficial as well as detrimental effects of activating KIR/HLA genotypes. It is likely that KIR/HLA association studies are complicated by the complexity of the KIR and HLA loci and their mutual interactions, as well as by additional factors like route of HIV exposure, immune activation, presence of co-infections, and the effect of anti-HIV-1 antibodies. One newly discovered NK cell activation pathway associated with resistance to HIV-1 infection involves the presence of an iKIR/HLA mismatch between partners. The absence of such an iKIR/HLA bond renders donor-derived allogeneic HIV-1 infected cells vulnerable to NK cell responses during HIV-1 transmission. Therefore, theoretically, HIV-1 would be eliminated before it has the chance to infect the autologous cells in the recipient. While this āalloreactiveā NK cell mechanism is especially relevant to HIV transmission in monogamous couples, it would be interesting to investigate how it could influence resistance to HIV in other settings. The objective of this review is to summarize the knowledge about these autologous and alloreactive NK cell responses with regard to HIV-1 outcome