Tumor suppressor WWOX and p53 alterations and drug resistance in glioblastomas

Tumor suppressor p53 are frequently mutated in glioblastomas (GBMs) and appears to contribute, in part, to resistance to temozolomide and therapeutic drugs. WW domain-containing oxidoreductase WWOX (FOR or WOX1) is a proapoptotic protein and is considered as a tumor suppressor. Loss of WWOX gene expression is frequently seen in malignant cancer cells due to promoter hypermethylation, genetic alterations, and translational blockade. Intriguingly, ectopic expression of wild type WWOX preferentially induces apoptosis in human glioblastoma cells harboring mutant p53. WWOX is known to physically bind and stabilize wild type p53. Here, we provide an overview for the updated knowledge in p53 and WWOX, and postulate a potential scenarios that wild type and mutant p53, or isoforms, modulate the apoptotic function of WWOX. We propose that triggering WWOX activation by therapeutic drugs under p53 functional deficiency is needed to overcome TMZ resistance and induce GBM cell death

The effect of aging in inhibitory control of major depressive disorder revealed by event-related potentials

Elderly depressed patients manifest pronounced executive dysfunction compared with younger subjects with depressive disorder. Aging-related brain changes may result in executive dysfunction in geriatric depression. We investigated the neural correlates of inhibitory control processing in depressed subjects at different ages using event-related potentials (ERPs). A equiprobable visual Go/Nogo task was used in 19 young (27.4 ± 5.0 years) and 18 elderly (70.8 ± 6.9 years) depressed subjects and their age-matched healthy controls (20 young subjects, 26.2 ± 3.7 years, and 18 elderly subjects, 68.1 ± 4.8 years). The responses were based on two types of equilateral triangular figures of upright (Go) and inverted triangle (Nogo). The elderly subjects exhibited later N2 and P3 latencies, and larger Go-N2 and P3 amplitudes, compared with the younger subjects. Further, the elderly controls displayed smaller P3 in the central and parietal regions, and yielded larger Nogo-P3 amplitude in the frontal region compared with younger controls. While the young depressed patients yielded smaller P3 amplitude than the controls across frontal, central and parietal regions, elderly depressed patients yielded smaller P3 than the elderly controls only in the frontal region. Our results suggest that the inhibitory control subprocesses are differentially affected by depression and aging. The stimulus response speed and the effort intensity of inhibition control are specifically impaired in the elderly depressed patients. And the diminished amplitudes of frontal P3 in the elderly depression imply a frontal dysfunction mechanism

Methylprednisolone protects cardiac pumping mechanics from deteriorating in lipopolysaccharide-treated rats

It has been shown that a prolonged low-dose corticosteroid treatment attenuates the severity of inflammation and the intensity and duration of organ system failure. In the present study, we determined whether low-dose methylprednisolone (a synthetic glucocorticoid) can protect male Wistar rats against cardiac pumping defects caused by lipopolysaccharide-induced chronic inflammation. For the induction of chronic inflammation, a slow-release ALZET osmotic pump was subcutaneously implanted to infuse lipopolysaccharide (1 mg kg−1 d−1) for 2 wk. The lipopolysaccharide-challenged rats were treated on a daily basis with intraperitoneal injection of methylprednisolone (5 mg kg−1 d−1) for 2 wk. Under conditions of anesthesia and open chest, we recorded left ventricular (LV) pressure and ascending aortic flow signals to calculate the maximal systolic elastance (Emax) and the theoretical maximum flow (Qmax), using the elastance-resistance model. Physically, Emax reflects the contractility of the myocardium as an intact heart, whereas Qmax has an inverse relationship with the LV internal resistance. Compared with the sham rats, the cardiodynamic condition was characterized by a decline in Emax associated with the increased Qmax in the lipopolysaccharide-treated rats. Methylprednisolone therapy increased Emax, which suggests that the drug may have protected the contractile status from deteriorating in the inflamed heart. By contrast, methylprednisolone therapy considerably reduced Qmax, indicating that the drug may have normalized the LV internal resistance. In parallel, the benefits of methylprednisolone on the LV systolic pumping mechanics were associated with the reduced cardiac levels of negative inotropic molecules such as peroxynitrite, malondialdehyde, and high-mobility group box 1 protein. Based on these data, we suggested that low-dose methylprednisolone might prevent lipopolysaccharide-induced decline in cardiac intrinsic contractility and LV internal resistance, possibly through its ability to reduce the aforementioned myocardial depressant substances. However, since our results were obtained in anesthetized open-chest rats, extrapolation to what may occur in conscious intact animals should be done with caution

Antecedent acute cycling exercise affects attention control: an ERP study using attention network test

The purpose of this study was to investigate the after-effects of an acute bout of moderate-intensity aerobic cycling exercise on neuroelectric and behavioral indices of efficiency of three attentional networks: alerting, orienting, and executive (conflict) control. Thirty young, highly fit amateur basketball players performed a multifunctional attentional reaction time task, the attention network test (ANT), with a two-group randomized experimental design after an acute bout of moderate-intensity spinning wheel exercise or without antecedent exercise. The ANT combined warning signals prior to targets, spatial cueing of potential target locations and target stimuli surrounded by congruent or incongruent flankers, which were provided to assess three attentional networks. Event-related brain potentials and task performance were measured during the ANT. Exercise resulted in a larger P3 amplitude in the alerting and executive control subtasks across frontal, central and parietal midline sites that was paralleled by an enhanced reaction speed only on trials with incongruent flankers of the executive control network. The P3 latency and response accuracy were not affected by exercise. These findings suggest that after spinning, more resources are allocated to task-relevant stimuli in tasks that rely on the alerting and executive control networks. However, the improvement in performance was observed in only the executively challenging conflict condition, suggesting that whether the brain resources that are rendered available immediately after acute exercise translate into better attention performance depends on the cognitive task complexity

Neural Mechanisms of Inhibitory Response in a Battlefield Scenario: a Simultaneous FMRI-EEG Study

The stop-signal paradigm has been widely adopted as a way to parametrically quantify the response inhibition process. To evaluate inhibitory function in realistic environmental settings, the current study compared stop-signal responses in two different scenarios: One uses simple visual symbols as go and stop signals, and the other translates the typical design into a battlefield scenario where a sniper-scope view was the background, a terrorist image was the go signal, a hostage image was the stop signal, and the task instructions were to shoot at terrorists only when hostages were not present but to refrain from shooting if hostages appeared. The battlefield scenario created a threatening environment and allowed the evaluation of how participants’ inhibitory control manifest in this realistic stop-signal task. In order to investigate the participants’ brain activities with both high spatial and temporal resolution, simultaneous functional magnetic resonance imaging (FMRI) and electroencephalography (EEG) recordings were acquired. The results demonstrated that both scenarios induced increased activity in the right inferior frontal gyrus (IFG) and presupplementary motor area (preSMA), which have been linked to response inhibition. Notably, in right temporoparietal junction (rTPJ) we found both higher BOLD activation and synchronization of theta-alpha activities (4-12 Hz) in the battlefield scenario than in the traditional scenario after the stop signal. The higher activation of rTPJ in the battle-field scenario may be related to morality judgments or attentional reorienting. These results provided new insights into the complex brain networks involved in inhibitory control within naturalistic environments

Survival and Growth of Epiphytic Ferns Depend on Resource Sharing

Locally available resources can be shared within clonal plant systems through physiological integration, thus enhancing their survival and growth. Most epiphytes exhibit clonal growth habit, but few studies have tested effects of physiological integration (resource sharing) on survival and growth of epiphytes and whether such effects vary with species. We conducted two experiments, one on individuals (single ramets) and another on groups (several ramets within a plot), with severed and intact rhizome treatments (without and with physiological integration) on two dominant epiphytic ferns (Polypodiodes subamoena and Lepisorus scolopendrium) in a subtropical montane moist forest in Southwest China. Rhizome severing (preventing integration) significantly reduced ramet survival in the individual experiment and number of surviving ramets in the group experiment, and it also decreased biomass of both species in both experiments. However, the magnitude of such integration effects did not vary significantly between the two species. We conclude that resource sharing may be a general strategy for clonal epiphytes to adapt to forest canopies where resources are limited and heterogeneously distributed in space and time