Signal transduction by protein tyrosine nitration: competition or cooperation with tyrosine phosphorylation-dependent signaling events?

This review article is an attempt to stimulate a discussion on the significance of protein tyrosine nitration to cellular signaling and its relationships with protein tyrosine phosphorylation. Initially, it provides basic information on growth factor and oxidants as modulators/mediators of tyrosine phosphorylation-dependent signal transduction pathways. The effects of exogenous and endogenous tyrosine nitration on such pathways were examined by reviewing published and unpublished observations. From an initial perspective that tyrosine nitration was a toxic manifestation of nitric oxide, the concept evolved to a protein modification that could also function in cellular signaling events, possibly cooperating with tyrosine phosphorylation.     

Metabolites predict cardiovascular disease events in persons living with HIV: a pilot case–control study

Introduction

Persons living with HIV (PLWH) are at higher risk for cardiovascular disease (CVD) events than uninfected persons. Current risk-stratification methods to define PLWH at highest risk for CVD events are lacking.

Methods

Using tandem flow injection mass spectrometry, we quantified plasma levels of 60 metabolites in 24 matched pairs of PLWH [1:1 with and without known coronary artery disease (CAD)]. Metabolite levels were reduced to interpretable factors using principal components analysis.

Results

Factors derived from short-chain dicarboxylacylcarnitines (SCDA) (p?=?0.08) and glutamine/valine (p?=?0.003) were elevated in CAD cases compared to controls.

Conclusion

SCDAs and glutamine/valine may be valuable markers of cardiovascular risk among persons living with HIV in the future, pending validation in larger cohorts.

     

Do mental events cause neural events analogously to the probability fields of quantum mechanics?

If non-material mental events, such as the intention to carry out an action, are to have an effective action on neural events in the brain, it has to be at the most subtle and plastic level of these events. In the first stage of our enquiry an introduction to conventional synaptic theory leads on to an account of the manner of operation of the ultimate synaptic units. These units are the synaptic boutons that, when excited by an all-or-nothing nerve impulse, deliver the total contents of a single synaptic vesicle, not regularly, but probabilistically. This quantal emission of the synaptic transmitter molecules (about 5000-10 000) is the elementary unit of the transmission process from one neuron to another. In the second stage this refined physiological analysis leads on to an account of the ultrastructure of the synapse, which gives clues as to the manner of its unitary probabilistic operation. The essential feature is that the effective structure of each bouton is a paracrystalline presynaptic vesicular grid with about 50 vesicles, which acts probabilistically in vesicular (quantal) release. In the third stage it is considered how a non-material mental event, such as an intention to move, could influence the subtle probabilistic operations of synaptic boutons. On the biological side, attention is focused on the paracrystalline presynaptic vesicular grids as the targets for non-material mental events. On the physical side, attention is focused on the probabilistic fields of quantum mechanics which carry neither mass nor energy, but which nevertheless can exert effective action at microsites. The new light on the mind-brain problem came from the hypothesis that the non-material mental events, the 'World 2' of Popper, relate to the neural events of the brain (the 'World 1' of matter and energy) by actions in conformity with quantum theory. This hypothesis that mental events act on probabilistic synaptic events in a manner analogous to the probability fields of quantum mechanics seems to open up an immense field of scientific investigation both in quantum physics and in neuroscience.     

Impaired modulation of circadian rhythms in patients with diabetes mellitus: a risk factor for cardiac thrombotic events?

Serious adverse cardiovascular events, including myocardial infarction, sudden cardiac death, and stroke, frequently result from rupture of atherosclerotic plaques with superimposed thrombosis and exhibit a pronounced circadian rhythmicity, peaking in the morning hours. Two potentially synergistic mechanisms play a pathogenic role in the circadian variation of arterial thrombotic events. A morning surge in sympathetic activity alters hemodynamic forces and predisposes vulnerable coronary atherosclerotic plaques to rupture. Day-night variations of hemostatic and fibrinolytic factors result in morning hypercoagulability and hypofibrinolysis, promoting intraluminal thrombus formation at the same time when the risk for plaque rupture is highest. Diabetic patients have a very high cardiac event rate but fail to show normal circadian fluctuations in the occurrence of myocardial infarction. Alterations in the circadian variation autonomic tone, blood pressure, and the thrombotic-thrombolytic equilibrium have been documented in diabetic patients. These include reduced or absent 24-h periodicity in autonomic tone, fibrinolytic activity, and thrombotic tendency, and a blunted decline in nocturnal blood pressure. Disruption of these circadian rhythms explains the lack of significant circadian distribution of cardiac events in diabetic patients. Moreover, the loss of these normal biorhythms results in a continuous susceptibility to thrombotic events throughout the day and may contribute to the excess cardiovascular mortality and morbidity in these patients. (Chronobiology International, 18(1), 109-121, 2001)     

Is pulse transit time useful in differentiating respiratory events for patients with a sleep breathing disorder? A pilot study

Variation of inspiratory effort in sleep disordered breathing induces the oscillation in blood pressure, which corresponds inversely to pulse transit time (PTT). This study evaluated the feasibility of PTT as a visual parameter for differentiating respiratory events in patients with a sleep breathing disorder. Sixteen patients who complained of snoring and sleep apnea were booked into the study. Polysomnographic data of Zopiclone induced daytime sleep were analyzed, PTT and intraesophageal pressure (Peso) were assessed for each respiratory event. With respect to Peso, the total accuracy of PTT was 51.8% for 1266 events. The relatively high coincidence rate could be observed in obstructive events (57.1%), with crescendo Peso pattern (71.5%), in lateral position (82.2%). Pulse transit time oscillation could only partly reflect respiratory rhythm to some degree (56.5%). Absolute PTT value presented a poor relationship with respiratory effort. Pulse transit time coincided well with crescendo Peso in lateral position for obstructive events. Swings in PTT could only partly fit respiratory wave data. Absolute PTT value and its change could not reflect respiratory effort. Although PTT is a non-invasive and convenient way for assessing inspiratory effort, its variable sensitivity to different events, respiratory patterns, positions, different patients and other situations, limit its feasibility. Further work is required.

     

Interaction between valence of empathy and familiarity: is it difficult to empathize with the positive events of a stranger?

Background

Empathy in humans is thought to have evolved via social interactions caused by the formation of social groups. Considering the role of empathy within a social group, there might be a difference between emotional empathy for strangers and familiar others belonging to the same social group. In this study, we used the global field power (GFP) index to investigate empathic brain activity during observation of a cue indicating either a negative or positive image viewed by a stranger or close friend.

Methods

Sixteen healthy participants observed a partner performing an emotional gambling task displayed on a monitor. After the partner''s choice-response, a frowning or smiling face symbol was simultaneously presented to the participant’s monitor while a negative or positive emotional image was presented to the partner’s monitor. All participants observed a control condition (CT) showing a computer trial, a stranger-observation condition (SO) showing the trial of a stranger, and a friend-observation condition (FO) to observe the trial of a close friend. During these observations, participants’ event-related potentials (ERPs) were recorded to calculate GFP, and after the task, a subjective assessment of their feelings was measured.

Results

Positive emotion was significantly larger under the FO compared to the CT and the SO. Significantly larger negative emotion was found under the SO and FO compared to the CT. In response to a positive cue, significantly larger GFP during 300 to 600 ms was observed under the FO compared to the CT and SO. In response to a negative cue, significantly larger GFP was observed under the FO and SO compared to the CT. A significantly larger GFP under the SO was found in response to only a negative cue. Topographic map analysis suggested that these differences were related to frontal-occipital dynamics. GFP was significantly correlated with empathic trait.

Conclusion

These results revealed that familiarity with another person has different effects depending on the valence of empathy. Negative empathy, including the danger perception function, might easily occur even among strangers, whereas positive empathy related to nursing and supporting an inner group does not happen easily with strangers.     

Kinetics of permeation and intracellular events associated with Me2SO permeation of rabbit kidneys during perfusion at 10 °C

The permeation kinetics of the cryoprotectant dimethylsulfoxide (Me₂SO) were investigated by the measure of total water, Me₂SO, and inulin spaces using radioactive tracers. Complete permeation of rabbit kidneys with a perfusate concentration of 3.0 M Me₂SO at 10 °C was obtained 35 min after reaching the maximum concentration when the cryoprotectant was introduced slowly. Equilibration was complete in the medulla before the cortex, probably due to the higher flow rates.Through study of the change in Me₂SO space and the inulin space, we were able to obtain evidence of cellular permeation of Me₂SO. In control kidneys, the inulin space decreased slightly during perfusion, an indication of cell swelling. Kidneys perfused with Me₂SO demonstrated a doubling of the inulin space, which did not decrease with time. The most likely explanation of this phenomenon is marked cell shrinkage, which was confirmed on histological examination and increased intraluminal tubular fluid. The picture is more complex since after intracellar equilibration, rehydration of the cell is not observed.     

Predicting primate responses to “Stochastic” demographic events

Comparative approaches in contemporary primate behavioral ecology have tended to emphasize the deterministic properties of stochastic ecological variables. Yet, primate responses to ecological fluctuations may be mediated by the interactions among demographic processes at the levels of individuals, groups, and populations. In this paper I examine long-term data collected from June 1982–July 1998 on one expanding group of muriquis (Brachyteles arachnoides) at the Estação Biologica de Caratinga, Minas Gerais, Brazil to explore the demographic and life history correlates of reproductive seasonality and skewed infant sex ratios. Variation in the size of annual birth cohorts (≥2 infants) was positively related to variation in the annual distribution of births (r _s=0.96,n=10,p<0.01), indicating the importance of considering the effects that the number of reproductive females may have on interpretations of reproductive seasonality. The female-biased infants sex ratio documented from 59 births was attributed exclusively to multiparous mothers. Primiparous mothers produced comparable numbers of sons (n=6) and daughters (n=7), and were increasingly likely to produce daughters with each subsequent reproductive event. Seven of the 11 females that have produced≥3 infants to date exhibited biases in favor of daughters whereas only 1 was biased in favor of sons. Variation in female sensitivity to local resource competition at different stages of their life histories may account for the female-biased infant sex ration in this population.     

How to model the events in cutaneous fibrosis?

Skin fibrosis is classically seen as the consequence of chronic inflammation and altered healing response that is characterized by the differentiation of fibroblasts into secretory myofibroblasts and accumulation of connective tissue. Although fibrosis severely affects organ function and causes esthetic defects, no effective therapy is currently available to attenuate the fibrogenic process probably because the fibrogenic process is more complex than previously thought. Indeed, it might involve several interacting and mutually dependent cell types (fibroblasts, keratinocytes, endothelial cells, inflammatory cells), numerous paracrine factors, bio-active molecules and micro-environmental stimuli (growth factors, vasoactive peptides, balance between pro- and anti-inflammatory cytokines, coagulation system, reactive oxygen species, extracellular matrix...). In this perspective, the traditional approach that model individual cell response in simple cell culture system is probably inadequate and too simplistic. This article reviews the new models used to study skin fibrosis in vitro, in organotypic culture systems and in vivo and examines how these different models might be used to identify new molecular pathways involved in fibrogenesis. The monolayer cultures allow the study of fibrogenic signals induced by a single factor on a single cell type. Isolation of cells from fibrotic tissue allows to define the fibrogenic differentiation acquired in vivo. The organotypic models allow cell to cell and cell to matrix interaction and the experimental models in pigs and mice allowed studies in integrated physiological systems. These various and complementary models would also provide new tools to develop and test new drugs and treatments.     

Is metabolic syndrome X a disorder of the brain with the initiation of low-grade systemic inflammatory events during the perinatal period?

An imbalance between pro- and anti-inflammatory molecules occurs in metabolic syndrome X. High-energy diet, saturated fats and trans-fats during perinatal period could suppress Delta(6) and Delta(5) desaturases both in the maternal and fetal tissues, resulting in a decrease in the concentrations of long-chain polyunsaturated fatty acids (LCPUFAs): arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) that have a negative feedback control on inflammation. EPA, DHA and AA augment endothelial nitric oxide synthesis, potentiate insulin action both in the peripheral tissues and brain and alter leptin production. LCPUFAs are essential for brain growth and development and synaptogenesis and modulate the action of several neurotransmitters and hypothalamic peptides. This suggests that metabolic syndrome X could be a disorder of the brain due to suboptimal LCPUFAs during perinatal period that triggers low-grade systemic inflammation, implying that perinatal strategies are needed to prevent its development.     

Early post-pollination events in hexaploid wheat × maize crosses

Summary Cytological events in the first 12 h after pollination were studied in crosses between the hexaploid wheat genotype Chinese Spring and the maize genotype Seneca 60. A pollen tube was first observed in the embryo sac 4 h after pollination, and maize sperm nuclei were first observed in the embryo sac after 5 h. On 29 occasions two, and on 1 occasion three, pollen tubes penetrated the embryo sac. Four categories of aberration limiting the frequency of fertilization were identified: (1) in 20% of florets no pollen tube reached the embryo sac; (2) in at least 1.9% the pollen tube severely damaged the wheat egg cell and polar nuclei; (3) in 33% the maize sperm nuclei were not released from the pollen tube; and (4) in 16% the sperm nuclei were released into the embryo sac but failed to move to either of the wheat gametes. In the remaining 29% sperm nuclei were more often found in the egg cell than at the polar nuclei. The results suggest that karyogamy occurs with very high efficiency when a sperm nucleus reaches the egg cell, but with only about 50% efficiency when a sperm nucleus reaches the polar nuclei.     

Is invasion efficiency in malaria controlled by pre-invasion events?

The invasion efficiency of Plasmodium falciparum merozoites was found to decrease with increasing red blood cell density, a finding relevant to protection strategies against falciparum malaria. The mechanism of this 'density effect' remained unexplained. Searching for possible explanations, we studied selected video recordings of the dynamic events during merozoite invasion and identified a pre-invasion stage as a crucial mediator of invasion efficiency. We suggest that the role of the pre-invasion stage is to induce the apical alignment of the merozoite, and propose a working hypothesis on its mechanism, with a crucial role for elevated intracellular Ca2+.     

European mink-polecat hybridization events: hazards from natural process?

Determining the significance of hybridization events raises essential issues both in conservation and in evolutionary biology. Here, we report a genetic investigation of sympatric polecat and endangered European mink populations. Although the two species were morphologically very similar, the European mink and the polecat were easily discriminated from allozymes and microsatellites and showed a high level of private alleles (effective number of alleles: mink=1.45 and polecat=3.09). Nevertheless, the allozymic polymorphism remained lower in the European mink (4 loci, 10.5%) than in polecat (9 loci, 23.7%). Similarly, from microsatellite data, the polymorphism only reached 36% at 0.99 in the European mink; whereas in the polecat, the polymorphism reached 82% at 0.99. Natural hybridization events between two native species were detected. Because of the low fertility of hybrids, interbreeding could be regarded as producing "hybrid sink" that leads to a progressive assimilation of mink by polecat. Nonetheless, pure mink populations inhabited streams in western France, and hybridization events were only detected in areas where mink were rare and now presumed disappeared. Rather than revealing the poor efficiency of the specific recognition system, our results suggest that hybridization is associated with the scarcity of mating partners.