In vitro propagation of Dactylosphaera vitifolii SHIMER (Homoptera: Phylloxeridae) on shoot and root cultures of a Vitis hybrid

Using a Vitis hybrid, methods of long-term micropropagation of shoots and culture of hairy roots (transformed by Agrobacterium rhizogenes) were developed. The growth of these organ cultures was characterized. The cultures were used as feeding substrates for grapevine phylloxera. Starting with eggs, at 23.6°C the parthenogenetic life cycle of the aphid proceeded in vitro. Within 2 weeks after inoculation, more than 80 % of the shoot cultures responded with the formation of galls on young leaf blades and swellings on petioles, and, exceptionally, young shoots. At about the same time new eggs were deposited. Gall formation and propagation of phylloxera could be perpetuated for 2.5 years by aseptical transfer of eggs to freshly micropropagated shoots every 1-3 weeks. Within 1 week after inoculation, more than 90 % of the younger parts of root cultures harboured larvae and responded with curvatures and thickenings. After 2 weeks, phylloxera oviposited and during the following weeks the number of eggs and animals increased considerably. Thus, both forms of dual culture enable leaf and root gall formation and propagation of phylloxera excluding further organisms

Precisely timed inhibition facilitates action potential firing for spatial coding in the auditory brainstem

The integration of excitatory and inhibitory synaptic inputs is fundamental to neuronal processing. In the mammalian auditory brainstem, neurons compare excitatory and inhibitory inputs from the ipsilateral and contralateral ear, respectively, for sound localization. However, the temporal precision and functional roles of inhibition in this integration process are unclear. Here, we demonstrate by in vivo recordings from the lateral superior olive (LSO) that inhibition controls spiking with microsecond precision throughout high frequency click trains. Depending on the relative timing of excitation and inhibition, neuronal spike probability is either suppressed or-unexpectedly-facilitated. In vitro conductance-clamp LSO recordings establish that a reduction in the voltage threshold for spike initiation due to a prior hyperpolarization results in post-inhibitory facilitation of otherwise sub-threshold synaptic events. Thus, microsecond-precise differences in the arrival of inhibition relative to excitation can facilitate spiking in the LSO, thereby promoting spatial sensitivity during the processing of faint sounds

Antibiotic use and risk of non-Hodgkin's lymphoma: a population-based case–control study

Antibiotic use in 759 non-Hodgkin's lymphoma (NHL) patients and 589 controls was compared. Neither total antibiotic use (odds ratio=0.7, 95% confidence interval=0.5–1.2), nor antibiotic use by site, was associated with total NHL, or NHL subtypes. There were no trends with frequency or age at first use (P trend=0.23 and 0.26, respectively)

The association between antihypertensive drugs and glioma

We pursued an association between hypertension and gliomas by investigating whether antihypertensive drugs (AHD) are associated with an increased glioma risk by a population-based nested case–control study using the PHARMO database; this links dispensing records of prescription drugs to hospital discharge data on an individual basis. Pathological data were derived from the Dutch nationwide registry of histo- and cytopathology. A total of 306 glioma cases incident between 1997 and 2003 were matched to 1108 controls for year of birth, sex, geographical region and duration of follow-up. Exposure was defined as cumulative duration of AHD use and, in an alternative analysis, as cumulative dose. We estimated the magnitude of the association with conditional logistic regression analysis. Cumulative use of any AHD for more than 6 months was associated with an increased risk of glioma (OR 1.45; 95% CI 1.03–2.04). After stratification for different groups of AHD, no significantly increased risk of glioma was found for any class of AHD. After excluding a latency period of 3 years before the date of diagnosis, no association was found. In conclusion, the use of AHD seems to be associated with an increased risk of glioma, but this is probably not causal

Chemical Proteomics-Based Analysis of Off-target Binding Profiles for Rosiglitazone and Pioglitazone: Clues for Assessing Potential for Cardiotoxicity

Drugs exert desired and undesired effects based on their binding interactions with protein target(s) and off-target(s), providing evidence for drug efficacy and toxicity. Pioglitazone and rosiglitazone possess a common functional core, glitazone, which is considered a privileged scaffold upon which to build a drug selective for a given target—in this case, PPARγ. Herein, we report a retrospective analysis of two variants of the glitazone scaffold, pioglitazone and rosiglitazone, in an effort to identify off-target binding events in the rat heart to explain recently reported cardiovascular risk associated with these drugs. Our results suggest that glitazone has affinity for dehydrogenases, consistent with known binding preferences for related rhodanine cores. Both drugs bound ion channels and modulators, with implications in congestive heart failure, arrhythmia, and peripheral edema. Additional proteins involved in glucose homeostasis, synaptic transduction, and mitochondrial energy production were detected and potentially contribute to drug efficacy and cardiotoxicity

Diazepam actions in the VTA enhance social dominance and mitochondrial function in the nucleus accumbens by activation of dopamine D1 receptors.

Benzodiazepines can ameliorate social disturbances and increase social competition, particularly in high-anxious individuals. However, the neural circuits and mechanisms underlying benzodiazepines' effects in social competition are not understood. Converging evidence points to the mesolimbic system as a potential site of action for at least some benzodiazepine-mediated effects. Furthermore, mitochondrial function in the nucleus accumbens (NAc) has been causally implicated in the link between anxiety and social competitiveness. Here, we show that diazepam facilitates social dominance, ameliorating both the competitive disadvantage and low NAc mitochondrial function displayed by high-anxious rats, and identify the ventral tegmental area (VTA) as a key site of action for direct diazepam effects. We also show that intra-VTA diazepam infusion increases accumbal dopamine and DOPAC, as well as activity of dopamine D1- but not D2-containing cells. In addition, intra-NAc infusion of a D1-, but not D2, receptor agonist facilitates social dominance and mitochondrial respiration. Conversely, intra-VTA diazepam actions on social dominance and NAc mitochondrial respiration are blocked by pharmacological NAc micro-infusion of a mitochondrial complex I inhibitor or an antagonist of D1 receptors. Our data support the view that diazepam disinhibits VTA dopaminergic neurons, leading to the release of dopamine into the NAc where activation of D1-signaling transiently facilitates mitochondrial function, that is, increased respiration and enhanced ATP levels, which ultimately enhances social competitive behavior. Therefore, our findings critically involve the mesolimbic system in the facilitating effects of diazepam on social competition and highlight mitochondrial function as a potential therapeutic target for anxiety-related social dysfunctions