BRMS1 contributes to the negative regulation of uPA gene expression through recruitment of HDAC1 to the NF-κB binding site of the uPA promoter

The BRMS1 metastasis suppressor was recently shown to negatively regulate NF-κB signaling and down regulate NF-κB-dependent uPA expression. Here we confirm that BRMS1 expression correlates with reduced NF-κB DNA binding activity in independently derived human melanoma C8161.9 cells stably expressing BRMS1. We show that knockdown of BRMS1 expression in these cells using small interfering RNA (siRNA) leads to the reactivation of NF-κB DNA binding activity and re-expression of uPA. Further, we confirm that BRMS1 expression does not alter IKKβ kinase activity suggesting that BRMS1-dependent uPA regulation does not occur through inhibition of the classical upstream activators of NF-κB. BRMS1 has been implicated as a corepressor of HDAC1 and consistent with this, we show that BRMS1 promotes HDAC1 recruitment to the NF-κB binding site of the uPA promoter and is associated with reduced H3 acetylation. We also confirm that BRMS1 expression stimulates disassociation of p65 from the NF-κB binding site of the uPA promoter consistent with its reduced DNA binding activity. These data suggest that BRMS1 recruits HDAC1 to the NF-κB binding site of the uPA promoter, modulates histone acetylation of p65 on the uPA promoter, leading to reduced NF-κB binding activity on its consensus sequence, and reduced transactivation of uPA expression.     

Do Helicobacter pylori therapeutic vaccines need to be tailored to the age of the recipient?

Helicobacter pylori infections typically commence during childhood and last for life. Freire de Melo and colleagues compared cytokine profiles in the stomachs of H. pylori-infected and H. pylori-uninfected children and adults from Brazil. They suggest that the immune effector response in infected children differs from infected adults, specifically that stomachs of infected children contained elevated regulatory T-cell markers and less IL-17 compared with adults. As vaccine-mediated protection against H. pylori is believed to involve IL-17 and to be inhibited by regulatory T cells, this raises the possibility that individual H. pylorivaccines may have different efficacies in children and adults.     

Is the antiepileptic effect of the ketogenic diet due to ketones?

For many years, the ketogenic diet, including recent variants such the medium-chain triglyceride (MCT) diet, has been used with good clinical results in the management of refractory epilepsies, particularly in children. The antiepileptic effects of the diet, like the antiepileptic effects of starvation, have been attributed to accumulation of ketones, and there are experimental data in animal models to support this hypothesis. Recently, new data about the neuroendocrine response to the acute phase reaction (stress) have emerged, indicating involvement of various neuropeptides, including neuropeptide Y (NPY), which is considered as an endogenous anticonvulsant. The release of NPY is also stimulated by nutrients in the gut, particularly fats. Long-chain and, to a greater extent, medium-chain triglycerides, which are components of the ketogenic diet, stimulate NPY secretion. This effect may explain the improvement in seizure control after starvation, use of the classical ketogenic diet, and use of the MCT diet.     

Preface to the Publication of Cellular ＆ Molecular Immunology

Immunology has made numerous important advances over the past decades and is at the forefront in uncovering the mechanisms of human immunological disorders and in eradicating pandemic infectious diseases. Immunological advances have also revealed the mystery of life and death and     

Transfer of the amyloid β and/or of β-amyloid precursor protein of the fetus with trisomy 21 to the maternal blood stream and its possible contribution to the pathogenesis of the maternal Alzheimer's Disease

Down Syndrome (DS) is the most frequent genetic pathology. It affects 1 out of every 800 newborn babies. Approximately between a 90% and a 95% of all the cases of DS are attributed to a trisomy in chromosome 21. One of the genes contained in this chromosome is the gene of β-amyloid precursor protein (βAPP). The metabolism of this protein yields, among others, the amyloid beta peptides made up of 40 amino acids (Aβ40) and 42 amino acids (Aβ42). The evidence that is derived from several sources - genetic, among them - suggests that the Aβ participates in the pathogenesis of Alzheimer’s Disease (AD).It is worth pointing at the fact that the transfer of cells, extracellular chromosomal material and some proteins from the fetus to the mother and vice versa has been widely described. The transfer rate from the fetus to the mother is higher when the mother is carrying a baby with trisomy 21. This has led to the hypothesis that sets forth that during the gestation of a baby with DS there is a greater fetomaternal transfer of cells and of products of the genes of chromosome 21 - among them, βAPP and its metabolites Aβ40 and Aβ42. It is possible to speculate on the possible contribution of the fetal components - among them, Aβ - to the higher risk of suffering AD, which has been reported in a subpopulation of women who have given birth to children with DS. On the other hand, the detection of the βAPP - mainly intracellular - and of the β amyloid peptides in maternal blood and urine during the early stages of gestation could be taken as a potential non invasive biochemical prenatal marker of DS.     

The kinematics of eating with a spoon: bringing the food to the mouth, or the mouth to the food?

In traditional reach-to-point and reach-to-grasp studies an increase in accuracy demands typically results in a lengthening of the deceleration phase of the reach and a freezing of the more distal joints. The purpose of the present experiment was to examine whether similar changes in the reach kinematics could be observed during a tool-using skill, as would be predicted from an effector independence perspective. Five subjects were required to eat two substances (i.e. a solid and a liquid one) that imposed different requirements on the accuracy of the movement. The subjects transported the substances from the plate into the mouth. A prolonged movement duration was found for the liquid as compared to the solid substance. However, rather than being exclusively due to a lengthening of deceleration phase, the larger movement duration resulted from a slowing down of the whole movement. Therefore, the skewed velocity profiles found in the traditional reach-to-grasp studies may well be the result of the accuracy demands only impinging on the final part of the movement trajectory, rather than being a consequence of central, effector-independent, organising principles. In addition, under increased accuracy demands subjects were shown to redistribute their movement in a proximodistal direction. Movements of the distal components were reduced to a minimum and the involvement of trunk and head movement increased. Received: 18 May 1998 / Accepted: 13 May 1999     

The Mitochondrial Permeability Transition Pore – a Regulator of the Resistance of the Heart to Reperfusion

Neuroscience and Behavioral Physiology - The most important event in the formation of reperfusion injury to the heart has been shown to be the opening of mitochondrial permeability transition pores...     

Compression Therapy to Prevent Recurrent Cellulitis of the Leg

Background:Chronic edema of the leg is a risk factor for cellulitis.Daily use of compression garments on the leg has been recommended to prevent the recurrence of cellulitis,but there is limited evidence from trials regarding its effectiveness.Methods:In this single-center,randomized,nonblinded trial,we assigned participants with chronic edema of the leg and recurrent cellulitis,in a 1:1 ratio,to receive leg compression therapy plus education on cellulitis prevention(compression group)or education alone(control group).Follow-up occurred every 6 months for up to 3 years or until 45 episodes of cellulitis had occurred in the trial.The primary outcome was the recurrence of cellulitis.     

Does proprioception contribute to the sense of verticality?

The representation of the vertical can be assessed by measuring the visual, tactile or perception of the postural vertical (PV). It is well accepted that visceral graviceptors and Golgi tendon receptors contribute to perception of the PV, whereas the role of muscular proprioception (Ia muscle spindles) remains to be clarified. The objective of this study was to analyze whether or not muscular proprioception contributes to the representation of verticality. We hypothesized that the modulation of proprioception by appropriate tendinomuscular vibration may tilt the PV. We present two experiments that explore this hypothesis. PV was firstly measured in the pitch plane in twelve healthy subjects in two conditions: baseline and vibration of both Achilles tendons during six minutes, according to a counterbalanced presentation. PV orientation (mean) and dispersion (standard deviation) were calculated on the six measurements per condition. Vibration of the Achilles tendons induced a systematic backward tilt of PV (2.7° ± 0.8° on average; P < 10⁻³), and no significant changes regarding PV dispersion. A clear post-effect was found for PV orientation in subjects who started the experiment with the condition vibration on. The possibility that PV could also be modulated by a much shorter duration of vibration (less than 8 s of vibration) was analyzed in a second experiment using a similar general procedure but a simplified experimental plane in other subjects. Again a backward PV tilt was induced by the vibration, but with a magnitude lower than that found in the first experiment, and with no post-effect. Since body geometry was unchanged, these two studies mean that proprioception contributes to the representation of the vertical. In conclusion, this study brings new insights to our understanding of the sense of verticality and contributes to the interpretation of backward falls induced by vibration. The induced backward fall is partly due to alignment of the erect posture with a backward-tilted referential of verticality.     

Contribution to the epidemiology of postnatal depression in Germany – implications for the utilization of treatment

Summary Using a longitudinal screening model, 772 mothers were screened for postnatal depression after delivery in Stuttgart (Germany). This model contained the Edinburgh Postnatal Depression Scale (EPDS) and the Hamilton Depression Scale (HAMD). The first screening was 6–8 weeks after delivery with the EPDS. Mothers with high scores in the first screening had a second screening 9–12 weeks after delivery with the EPDS at least three weeks after the first. Mothers with high scores in both screenings were investigated with the Hamilton Depression Scale (HAMD).Classification was performed with the DSM-IV. After observation until the third month after delivery, 3.6% (N = 28) of the 772 mothers were diagnosed with postnatal depression. Various methods of therapy were offered to those mothers. 18% (N = 5) accepted one or more of these methods of treatment. The rest of the mothers with postnatal depression refused – mostly for attitudinal or practical reasons. 13.4% of the mothers showed high scores in the first screening but not in the second. For those mothers a longitudinal observation is currently being performed to distinguish between a depressive episode and a depression with oscillating symptoms.     

How do infants adapt to loading of the limb during the swing phase of stepping?

Previous results from this laboratory have shown that human infants (<12 mo old) respond appropriately to transient changes in sensory input during stepping. We examined how infants adapted to a more enduring change in sensory input by applying load to one limb during stepping. A small weight (500-900 g) was strapped around the lower leg of infants aged 3-11 mo. Stepping with the weight on was recorded on the treadmill for a period of 0.5-3 min. The weight was then quickly detached during stepping, and the immediate response to unexpected loss of the weight recorded. Three-segment dynamic analysis of leg motion was used to estimate hip, knee, and ankle torques during swing in the sagittal plane. All infants adapted to the additional load on the leg by immediately increasing the generation of hip and knee flexor muscle torques. When the weight was removed, 7 of the 22 infants tested exhibited an after-effect (high stepping) in the first step after removal of the weight. The after-effect was manifested as an increase in toe trajectory height and hip flexion and coincided with higher hip flexor muscle torque in early swing. In an additional series of control experiments using seven infants, after-effects were shown to be unrelated to a sudden change in cutaneous input with removal of the weight. The presence of an after-effect indicates that some infants made an enduring adaptation to their stepping pattern that is revealed with the unexpected removal of the weight.