Characterization of the Novel P2X7 Receptor Radioligand [³H]JNJ-64413739 in Human Brain Tissue

Radioligands targeting microglia cells have been developed to identify and determine neuroinflammation in the living brain. One recently discovered ligand is JNJ-64413739 that binds selectively to the purinergic receptor P2X7R. The expression of P2X7R is increased under inflammation; hence, the ligand is considered useful in the detection of neuroinflammation in the brain. [18F]JNJ-64413739 has been evaluated in healthy subjects with positron emission tomography; however, the in vitro binding properties of the ligand in human brain tissue have not been investigated. Therefore, the purpose of this study was to measure Bmax and Kd of [3H]JNJ-64413739 using autoradiography on human cortical tissue sections resected from a total of 48 patients with treatment-resistant epilepsy. Correlations between the specific binding of [3H]JNJ-64413739 with age, sex, and duration of disease were explored. Finally, to examine the relationship between P2X7R and TSPO availability, specific binding of [3H]JNJ-64413739 and [123I]CLINDE was examined in the same tissue. The binding was measured in both cortical gray and subcortical white matter. Saturation revealed a Kd (5 nM) value similar between gray and white matter but a larger Bmax in the white than in the gray matter. The binding was completely displaced by the cold ligand and structurally different P2X7R ligands. The variability in saturable binding among the samples was found to be 38% in gray and white matter but was not correlated to either age, sex, or the duration of the disease. Interestingly, there was no significant correlation between [3H]JNJ-64413739 and [123I]CLINDE binding. These data demonstrate that [3H]JNJ-64413739 is a suitable radioligand for evaluating the distribution and expression of the P2X7R in the human brain.</p

Crop losses in Brazilian cassava varieties induced by the Cassava common mosaic virus

ABSTRACT Despite the widespread distribution of the Cassava common mosaic virus (CsCMV) in Brazil, little is known about the losses it causes in yield. The effect of CsCMV on different varieties was evaluated by reference to several agronomic traits. Four field trials were established in 2012/2013 and 2013/2014 using six varieties of cassava. Following mechanical inoculation with CsCMV, the presence of the virus was confirmed using the ELISA assay. The evaluated traits were plant height (PH), dry matter content (DMC), harvest index (HI), aerial part yield (APY), root yield (RoY), and starch yield (StY) in both inoculated and non-inoculated plants. Overall, the presence of the virus contributed little to the reduction in PH, HI, and DMC across the varieties, with PH being significantly reduced by 9.2 and 7.0 % in the BGM0212 and BRS Kiriris varieties, respectively. In contrast, APY, RoY, and StY were reduced by 30.2, 29.3, and 30.0 %, in the virus-infected plants respectively. While the BRS Kiriris and BRS Jari varieties suffered the highest reductions overall and were considered highly susceptible to CsCMV, none of the traits suffered reductions in the inoculated BRS Formosa plants. Although RoY and StY were reduced in inoculated plants of BRS Tapioqueira, crop yield for this variety was the highest. Thus, BRS Formosa and BRS Tapioqueira exhibited tolerance against CsCMV, which warrants further investigation

Exogenous pipecolic acid modulates plant defence responses against Podosphaera xanthii and Pseudomonas syringae pv. lachrymans in cucumber (Cucumis sativus L.)

PAZARLAR, Sercan/0000-0002-3768-4923; SANVER, UTKU/0000-0001-5373-2924WOS:000621218500001PubMed: 33547740Systemic acquired resistance (SAR) is a long-lasting and broad-based resistance that can be activated following infection with (a)virulent pathogens and treatment with exogenous elicitors. Pipecolic acid (Pip), a Lys-derived non-protein amino acid, naturally occurs in many different plant species, and its N-hydroxylated derivative, N-hydroxypipecolic acid (NHP), acts as a crucial regulator of SAR. in the present study, we conducted a systemic analysis of the defence responses of a series of D,L-Pip-pretreated Cucumis sativus L. against Podosphaera xanthii (P. xanthii) and Pseudomonas syringae pv. lachrymans (Psl). The effects of D,L-Pip on ROS metabolism, defence-related gene expression, SA accumulation and activity of defence-related enzymes were evaluated. We show that exogenously applied D,L-Pip successfully induces SAR in cucumber against P. xanthii and Psl, but not Fusarium oxysporum f. sp. cucumerinum (Foc). Exogenous application of D,L-Pip via the root system is sufficient to activate the accumulation of free and conjugated salicylic acid (SA), and earlier and stronger upregulation of SAR-associated gene transcription upon P. xanthii infection. Furthermore, D,L-Pip treatment and subsequent pathogen inoculation promote hydrogen peroxide and superoxide accumulation, as well as Rboh transcription activation in cucumber plants, suggesting that D,L-Pip-triggered ROS production might be involved in enhanced defence reactions against P. xanthii. We also demonstrate that D,L-Pip pretreatment increases the activity of defence-associated enzymes, including peroxidase, chitinase and beta-1,3-glucanase. The results presented in this report provide promising features of Pip as an elicitor in cucumber and call for further studies that may uncover its potential in production areas against different phytopathogens

First Report of Pseudomonas viridiflava Causing Bacterial Blight on Globe Artichoke in Turkey

WOS: 00047769240004

Binding of the monoacylglycerol lipase (MAGL) radiotracer [³H]T-401 in the rat brain after status epilepticus

ObjectivesMonoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase considered a potential novel drug target for the treatment of CNS disorders including epilepsy. Here we examined MAGL levels in a rat model of epilepsy.MethodsAutoradiography has been used to validate the binding properties of the MAGL radiotracer, [3H]T-401, in the rat brain, and to explore spatial and temporal changes in binding levels in a model of temporal lobe epilepsy model using unilateral intra-hippocampal injections of kainic acid (KA) in rats.ResultsSpecific and saturable binding of [3H]T-401 was detected in both cortical grey and subcortical white matter. Saturation experiments revealed a KD in the range between 15 nM and 17 nM, and full saturation was achieved at concentrations around 30 nM. The binding could be completely blocked with the cold ligand (Ki 44.2 nM) and at higher affinity (Ki 1.27 nM) with another structurally different MAGL inhibitor, ABD 1970.Bilateral reduction in [3H]T-401 binding was observed in the cerebral cortex and the hippocampus few days after status epilepticus that further declined to a level of around 30% compared to the control. No change in binding was observed in either the hypothalamus nor the white matter at any time point. Direct comparison to [3H]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A), another protein localized in the pre-synapse, revealed that while binding to MAGL remained low in the chronic phase, SV2A was increased significantly in some cortical areas.SignificanceThese data show that MAGL is reduced in the cerebral cortex and hippocampus in a chronic epilepsy model and indicate that MAGL inhibitors may further reduce MAGL activity in the treatment resistant epilepsy patient.Objectives: Monoacylglycerol lipase (MAGL) is a cytosolic serine hydrolase considered a potential novel drug target for the treatment of CNS disorders including epilepsy. Here we examined MAGL levels in a rat model of epilepsy. Methods: Autoradiography has been used to validate the binding properties of the MAGL radiotracer, [3H]T-401, in the rat brain, and to explore spatial and temporal changes in binding levels in a model of temporal lobe epilepsy model using unilateral intra-hippocampal injections of kainic acid (KA) in rats. Results: Specific and saturable binding of [3H]T-401 was detected in both cortical grey and subcortical white matter. Saturation experiments revealed a KD in the range between 15 nM and 17 nM, and full saturation was achieved at concentrations around 30 nM. The binding could be completely blocked with the cold ligand (Ki 44.2 nM) and at higher affinity (Ki 1.27 nM) with another structurally different MAGL inhibitor, ABD 1970. Bilateral reduction in [3H]T-401 binding was observed in the cerebral cortex and the hippocampus few days after status epilepticus that further declined to a level of around 30% compared to the control. No change in binding was observed in either the hypothalamus nor the white matter at any time point. Direct comparison to [3H]UCB-J binding to synaptic vesicle glycoprotein 2 A (SV2A), another protein localized in the pre-synapse, revealed that while binding to MAGL remained low in the chronic phase, SV2A was increased significantly in some cortical areas. Significance: These data show that MAGL is reduced in the cerebral cortex and hippocampus in a chronic epilepsy model and indicate that MAGL inhibitors may further reduce MAGL activity in the treatment resistant epilepsy patient.</p