Is the Cytosolic Pi Concentration a Limiting Factor for Plant Cell Respiration?

The substrate-dependent O₂ uptake by sycamore (Acer pseudoplatanus L.) cell mitochondria in the presence of ADP and limiting Pi concentrations has been measured. The Pi concentration for half-maximum O₂ uptake rate was found to be in the range 20 to 50 micromolar for all the substrates tested. ³¹P NMR of intact sycamore cells indicated that the Pi concentration in the cytoplasm was in the range 5 to 6 millimolar, approximately 100-fold higher than the Pi concentration required for maximum O₂ uptake rates by isolated mitochondria. When sycamore cells were transferred to a culture medium devoid of Pi, the cytoplasmic Pi concentration decreased from 6 to less than 3 millimolar, but the intact cell respiration remained practically constant for at least 4 days. These results strongly suggest that, in vivo, the respiration rate of sycamore cells is not limited by the quantity of Pi supplied to the mitochondria.     

Brain Switches Utilitarian Behavior: Does Gender Make the Difference?

Decision often implies a utilitarian choice based on personal gain, even at the expense of damaging others. Despite the social implications of utilitarian behavior, its neurophysiological bases remain largely unknown. To assess how the human brain controls utilitarian behavior, we delivered transcranial direct current stimulation (tDCS) over the ventral prefrontal cortex (VPC) and over the occipital cortex (OC) in 78 healthy subjects. Utilitarian judgment was assessed with the moral judgment task before and after tDCS. At baseline, females provided fewer utilitarian answers than males for personal moral dilemmas (p = .007). In males, VPC-tDCS failed to induce changes and in both genders OC-tDCS left utilitarian judgments unchanged. In females, cathodal VPC-tDCS tended to decrease whereas anodal VPC-tDCS significantly increased utilitarian responses (p = .005). In males and females, reaction times for utilitarian responses significantly decreased after cathodal (p<.001) but not after anodal (p = .735) VPC-tDCS. We conclude that ventral prefrontal tDCS interferes with utilitarian decisions, influencing the evaluation of the advantages and disadvantages of each option in both sexes, but does so more strongly in females. Whereas cathodal tDCS alters the time for utilitarian reasoning in both sexes, anodal stimulation interferes more incisively in women, modifying utilitarian reasoning and the possible consequent actions. The gender-related tDCS-induced changes suggest that the VPC differentially controls utilitarian reasoning in females and in males. The gender-specific functional organization of the brain areas involved in utilitarian behavior could be a correlate of the moral and social behavioral differences between the two sexes.     

Is Obesity a Risk Factor for Vaccine Non-Responsiveness?

Understanding the link between vaccine immunogenicity and efficacy is currently a major focus in HIV research. Consequently, recent developments in the HIV-1 vaccine field have led to a closer look at immune responses to known efficacious vaccines. We undertook a study to explore clinical predictors of vaccine efficacy following recombinant hepatitis B (rHBV) vaccination in a cohort of HIV-uninfected, hepatitis B virus naïve women living in a peri-urban setting in Cape Town. Our aim was to define host biological risk factors associated with lack of vaccine uptake. We found a significant association (p=0.009) between body mass index (BMI) and lack of vaccine-specific IgG titre (<10mIU/mL). Obese individuals (BMI ≥ 30kg/m²) were significantly more likely to be non-responders following 2 rHBV vaccine doses (Adjusted Odds Ratio of 8.75; p=0.043). There was no observed association between vaccine responses and age, method of contraception or time from vaccination to antibody measurement. These data suggest that obesity-associated factors interfere with vaccine immunogenicity and possible efficacy.     

Does the Clock Make the Poison? Circadian Variation in Response to Pesticides

Background

Circadian clocks govern daily physiological and molecular rhythms, and putative rhythms in expression of xenobiotic metabolizing (XM) genes have been described in both insects and mammals. Such rhythms could have important consequences for outcomes of chemical exposures at different times of day. To determine whether reported XM gene expression rhythms result in functional rhythms, we examined daily profiles of enzyme activity and dose responses to the pesticides propoxur, deltamethrin, fipronil, and malathion.

Methodology/Principal Findings

Published microarray expression data were examined for temporal patterns. Male Drosophila were collected for ethoxycoumarin-O-deethylase (ECOD), esterase, glutathione-S-transferase (GST), and, and uridine 5′-diphosphoglucosyltransferase (UGT) enzyme activity assays, or subjected to dose-response tests at four hour intervals throughout the day in both light/dark and constant light conditions. Peak expression of several XM genes cluster in late afternoon. Significant diurnal variation was observed in ECOD and UGT enzyme activity, however, no significant daily variation was observed in esterase or GST activity. Daily profiles of susceptibility to lethality after acute exposure to propoxur and fipronil showed significantly increased resistance in midday, while susceptibility to deltamethrin and malathion varied little. In constant light, which interferes with clock function, the daily variation in susceptibility to propoxur and in ECOD and UGT enzyme activity was depressed.

Conclusions/Significance

Expression and activities of specific XM enzymes fluctuate during the day, and for specific insecticides, the concentration resulting in 50% mortality varies significantly during the day. Time of day of chemical exposure should be an important consideration in experimental design, use of pesticides, and human risk assessment.     

Could a Factor That Does Not Affect Egg Recognition Influence the Decision of Rejection?

Rejection of the parasitic egg is the most important defence of hosts against brood parasites. However, this response is variable among and within species, and egg discrimination is not always followed by egg rejection. Low risk of parasitism and high risk of rejection costs may lead to the acceptance of the parasitic egg even if it has been previously recognized. The main aim of this paper is to answer a relevant question: can a single egg trait provoke the acceptance of an experimental egg previously recognized as foreign? Increased egg mass should hamper the ejection of an egg that has been discriminated because ejection of a heavy egg may imply higher rejection costs for hosts. We have tested this prediction by experimentally parasitizing natural nests of Common Blackbirds (Turdus merula) with non-mimetic model eggs of different mass (heavy, normal-weight, and light) while controlling for potential confounding factors such as egg size and colour. Our results showed that blackbirds more frequently accepted heavy eggs, even when previously recognized. This differential acceptance may be related to insufficient motivation to assume the higher costs that the ejection of a heavy egg could impose.     

Does the anterior cruciate have a modeling threshold? A case for the affirmative

Growing evidence supports a 1972 proposal that dynamic tension strains of a ligament above a threshold range, but below its ultimate strength, would make its cells synthesize more collagen to thicken and strengthen it. If so, when that strengthening reduced later strains to the bottom of that threshold range this "diametric modeling" would stop. A) Such a mechanism must create a "strength-safety factor" that would minimize or prevent voluntary activities from rupturing healthy ligaments, so chiefly injuries would rupture them. B) Such a mechanism should also make the usual largest loads on a healthy anterior cruciate ligament (ACL) determine its strength, and would make smaller loads mixed with large ones have little effect on its strength. C) In principle, when an ACL's strains exceeded that threshold range, diametric modeling would turn on, strengthen it, and reduce subsequent strains from the same loads. When its strains remained smaller, this mechanically-controlled modeling would turn off. Normal ACLs do have a strength-safety factor so they could have a diametric modeling threshold too, as we now know bone does. In healthy young adult humans available evidence suggests that threshold's value could lie in the region of 23 Newtons/mmC of the ACL's cross section area. If similar relationships applied to fascia, tendons and other ligaments (I suggest they do), they would form fundamental biomechanical properties of collagenous tissue organs.     

Projection of Young-Old and Old-Old with Functional Disability: Does Accounting for the Changing Educational Composition of the Elderly Population Make a Difference?

This study compares projections, up to year 2040, of young-old (aged 60-79) and old-old (aged 80+) with functional disability in Singapore with and without accounting for the changing educational composition of the Singaporean elderly. Two multi-state population models, with and without accounting for educational composition respectively, were developed, parameterized with age-gender-(education)-specific transition probabilities (between active, functional disability and death states) estimated from two waves (2009 and 2011) of a nationally representative survey of community-dwelling Singaporeans aged ≥60 years (N=4,990). Probabilistic sensitivity analysis with the bootstrap method was used to obtain the 95% confidence interval of the transition probabilities. Not accounting for educational composition overestimated the young-old with functional disability by 65 percent and underestimated the old-old by 20 percent in 2040. Accounting for educational composition, the proportion of old-old with functional disability increased from 40.8 percent in 2000 to 64.4 percent by 2040; not accounting for educational composition, the proportion in 2040 was 49.4 percent. Since the health profiles, and hence care needs, of the old-old differ from those of the young-old, health care service utilization and expenditure and the demand for formal and informal caregiving will be affected, impacting health and long-term care policy.     

Is Iron Accumulation a Possible Risk Factor for Sarcopenia?

Sarcopenia has a high incidence among the elderly, with significant negative effects on the quality of life. The pathogenesis of sarcopenia is complex, and many factors are involved in its development and progression. Sarcopenia might be associated with iron accumulation given that (1) age-related iron accumulation was found in the skeletal muscle, (2) excess iron could cause skeletal muscle damage or atrophy, and (3) patients with sarcopenia showed higher levels of serum ferritin. Understanding the etiology and pathogenesis of sarcopenia would help to develop new treatment and preventive methods, thereby improving the quality of life of the elderly patients.     

Does the pentose cycle play a major role for NADPH supply in the heart?

It was attempted to determine the substrate flux through the pentose cycle in isolated rat hearts which performed pressure-volume work employing 14CO2 production from [1-14C]glucose (Kühn & Scholz (1982) Eur. J. Biochem. 124, 611-617). Even under conditions of increased NADPH requirements (infusion of tert-butylhydroperoxide) and a diminished 14CO2 production from glucose via the citrate cycle (in the presence of oleate as additional substrate) or enhanced activity of glucose-6-phosphate dehydrogenase (pretreatment with isoproterenol), a substrate flux through the pentose cycle was not detectable. The lower limit of detection is 0.01 mumol/(min X g). The increase in 14CO2 production from [1-14C]- and [6-14C]glucose and the acceleration in the washout when tert-butylhydroperoxide was present suggest an increase of substrate flux through the citrate cycle; therefore it is concluded that NADPH required for the removal of peroxides via the glutathione system is derived from the isocitrate dehydrogenase reaction.     

Is RsfS a Hibernation Factor or a Ribosome Biogenesis Factor?

Biochemistry (Moscow) - Solving the structures of bacterial, archaeal, and eukaryotic ribosomes by crystallography and cryo-electron microscopy has given an impetus for studying intracellular...     

Does Phospholipid Methylation Play a Role in the Primary Mechanism of Action of Nerve Growth Factor?

Nerve growth factor (NGF)-untreated (naive) and neurite-bearing NGF-treated ("primed") PC12 rat pheochromocytoma cells were used as model system to study the role of phospholipid methylation in the NGF mechanism of action. The neurite-bearing cultures were deprived of NGF for 3 h before experimentation. Under both experimental conditions, the cells were labelled with [methyl-3H]methionine and then challenged with NGF for time periods ranging from 5 s to 30 min. Methylated phospholipids were extracted and then resolved and identified by TLC as phosphatidyl mono-, di-, and trimethyl ethanolamine. Quantification of the amount of radioactivity incorporated into each of the phospholipids indicated that NGF does not significantly alter phospholipid methylation either in naive or in neurite-bearing cells. Furthermore, using a methyltransferase inhibitor, it was found that neurite outgrowth still occurs when phospholipid methylation is almost completely blocked. These results indicate that phospholipid methylation does not play a primary role in the mechanism of action of NGF.     

The Social Bayesian Brain: Does Mentalizing Make a Difference When We Learn?

When it comes to interpreting others'' behaviour, we almost irrepressibly engage in the attribution of mental states (beliefs, emotions…). Such "mentalizing" can become very sophisticated, eventually endowing us with highly adaptive skills such as convincing, teaching or deceiving. Here, sophistication can be captured in terms of the depth of our recursive beliefs, as in "I think that you think that I think…" In this work, we test whether such sophisticated recursive beliefs subtend learning in the context of social interaction. We asked participants to play repeated games against artificial (Bayesian) mentalizing agents, which differ in their sophistication. Critically, we made people believe either that they were playing against each other, or that they were gambling like in a casino. Although both framings are similarly deceiving, participants win against the artificial (sophisticated) mentalizing agents in the social framing of the task, and lose in the non-social framing. Moreover, we find that participants'' choice sequences are best explained by sophisticated mentalizing Bayesian learning models only in the social framing. This study is the first demonstration of the added-value of mentalizing on learning in the context of repeated social interactions. Importantly, our results show that we would not be able to decipher intentional behaviour without a priori attributing mental states to others.     

Sexual Behaviour: Do a Few Dead Neurons Make the Difference?

Why do males and females behave so differently? Sexually dimorphic neural circuitry has just been found in parts of the fly's brain thought to control mating behaviour. Might this explain why males and females have such distinct sexual behaviours?