Dog bites man or man bites dog? The enigma of the amino acid conjugations

The proposition posed is that the value of amino acid conjugation to the organism is not, as in the traditional view, to use amino acids for the detoxication of aromatic acids. Rather, the converse is more likely, to use aromatic acids that originate from the diet and gut microbiota to assist in the regulation of body stores of amino acids, such as glycine, glutamate, and, in certain invertebrates, arginine, that are key neurotransmitters in the central nervous system (CNS). As such, the amino acid conjugations are not so much detoxication reactions, rather they are homeostatic and neuroregulatory processes. Experimental data have been culled in support of this hypothesis from a broad range of scientific and clinical literature. Such data include the low detoxication value of amino acid conjugations and the Janus nature of certain amino acids that are both neurotransmitters and apparent conjugating agents. Amino acid scavenging mechanisms in blood deplete brain amino acids. Amino acids glutamate and glycine when trafficked from brain are metabolized to conjugates of aromatic acids in hepatic mitochondria and then irreversibly excreted into urine. This process is used clinically to deplete excess nitrogen in cases of urea cycle enzymopathies through excretion of glycine or glutamine as their aromatic acid conjugates. Untoward effects of high-dose phenylacetic acid surround CNS toxicity. There appears to be a relationship between extent of glycine scavenging by benzoic acid and psychomotor function. Glycine and glutamine scavenging by conjugation with aromatic acids may have important psychosomatic consequences that link diet to health, wellbeing, and disease.

Comparing skew Schur functions: a quasisymmetric perspective

Reiner, Shaw and van Willigenburg showed that if two skew Schur functions sA and sB are equal, then the skew shapes $A$ and $B$ must have the same "row overlap partitions." Here we show that these row overlap equalities are also implied by a much weaker condition than Schur equality: that sA and sB have the same support when expanded in the fundamental quasisymmetric basis F. Surprisingly, there is significant evidence supporting a conjecture that the converse is also true. In fact, we work in terms of inequalities, showing that if the F-support of sA contains that of sB, then the row overlap partitions of A are dominated by those of B, and again conjecture that the converse also holds. Our evidence in favor of these conjectures includes their consistency with a complete determination of all F-support containment relations for F-multiplicity-free skew Schur functions. We conclude with a consideration of how some other quasisymmetric bases fit into our framework.

Parental understanding of wheeze and its impact on asthma prevalence estimates

The epidemiology of wheeze in children, when assessed by questionnaires, is dependent on parents' understanding of the term "wheeze". In a questionnaire survey of a random population sample of 4,236 children aged 6-10 yrs, parents' definition of wheeze was assessed. Predictors of a correct definition were determined and the potential impact of incorrect answers on prevalence estimates from the survey was assessed. Current wheeze was reported by 13.2% of children. Overall, 83.5% of parents correctly identified "whistling or squeaking" as the definition of wheeze; the proportion was higher for parents reporting wheezy children (90.4%). Frequent attacks of reported wheeze (adjusted odds ratio (OR) 3.0), maternal history of asthma (OR 1.5) and maternal education (OR 1.5) were significantly associated with a correct answer, while the converse was found for South Asian ethnicity (OR 0.6), first language not English (OR 0.6) and living in a deprived neighbourhood (OR 0.6). In summary, the present study showed that misunderstanding could lead to an important bias in assessing the prevalence of wheeze, resulting in an underestimation in children from South Asian and deprived family backgrounds. Prevalence estimates for the most severe categories of wheeze might be less affected by this bias and questionnaire surveys on wheeze should incorporate measures of parents' understanding of the term wheeze.

Continuum percolation for Gibbs point processes

We consider percolation properties of the Boolean model generated by a Gibbs point process and balls with deterministic radius. We show that for a large class of Gibbs point processes there exists a critical activity, such that percolation occurs a.s. above criticality. For locally stable Gibbs point processes we show a converse result, i.e. they do not percolate a.s. at low activity.

Sp1 up-regulates cAMP-response-element-binding protein expression during retinoic acid-induced mucous differentiation of normal human bronchial epithelial cells.

CREB [CRE (cAMP-response element)-binding protein] is an important transcription factor that is differentially regulated in cells of various types. We recently reported that RA (retinoic acid) rapidly activates CREB without using RARs (RA receptors) or RXRs (retinoid X receptors) in NHTBE cells (normal human tracheobronchial epithelial cells). However, little is known about the role of RA in the physiological regulation of CREB expression in the early mucous differentiation of NHTBE cells. In the present study, we report that RA up-regulates CREB gene expression and that, using 5'-serial deletion promoter analysis and mutagenesis analyses, two Sp1 (specificity protein 1)-binding sites located at nt -217 and -150, which flank the transcription initiation site, are essential for RA induction of CREB gene transcription. Furthermore, we found that CREs located at nt -119 and -98 contributed to basal promoter activity. Interestingly, RA also up-regulated Sp1 in a time- and dose-dependent manner. Knockdown of endogenous Sp1 using siRNA (small interfering RNA) decreased RA-induced CREB gene expression. However, the converse was not true: knockdown of CREB using CREB siRNA did not affect RA-induced Sp1 gene expression. We conclude that RA up-regulates CREB gene expression during the early stage of NHTBE cell differentiation and that RA-inducible Sp1 plays a major role in up-regulating human CREB gene expression. This result implies that co-operation of these two transcription factors plays a crucial role in mediating early events of normal mucous cell differentiation of bronchial epithelial cells.

Evaluation of androgenicity, abdominal adiposity, blood pressure and types of ovulatory patterns in a sample of women with menstrual irregularities

Objective: To determine the prevalence of and the relationships between the degree and source of hyperandrogenemia, ovulatory patterns and cardiovascular disease risk indicators (blood pressure, indices or amount of obesity and fat distribution) in women with menstrual irregularities seen at endocrinologists' clinic. Design: A cross-sectional study design. Participants: A sample of 159 women with menstrual irregularities, aged 15-44, seen at endocrinologists' clinic. Main Outcome Measures: androgen levels, body mass index (BMI), waist-hip ratio (WHR), systolic and diastolic blood pressure (SBP & DBP), source of androgens, ovulatory activity. Results: The prevalence of hyperandrogenemia was 54.7% in this study sample. As expected, women with acne or hirsutism had an odds ratio 12.5 (95%CI = 5.2-25.5) times and 36 (95%CI = 12.9-99.5) times more likely to have hyperandrogenemia than those without acne or hirsutism. The main findings of this study were the following: Hyperandrogenemic women were more likely to have oligomenorrheic cycles (OR = 3.8, 95%CI = 1.5-9.9), anovulatory cycles (OR = 6.6, 95%CI = 2.8-15.4), general obesity (BMI $\ge$ 27) (OR = 6.8, 95%CI = 2.2-27.2) and central obesity (WHR $\ge$ 127) (OR = 14.5, 95%CI = 6.1-38.7) than euandrogenemic women. Hyperandrogenemic women with non-suppressible androgens had a higher mean BMI (29.3 $\pm$ 8.9) than those with suppressible androgens (27.9 $\pm$ 7.9); the converse was true for abdominal adiposity (WHR). Hyperandrogenemic women had a 2.4 odds ratio (95%CI = 1.0-6.2) for an elevated SBP and a 2.7 odds ratio (95%CI = 0.8-8.8) for elevated DBP. When age differences were accounted for, this relationship was strengthened and further strengthened when sources of androgens were controlled. When the differences in BMI were controlled, the odds ratio for elevated SBP in hyperandrogenemic women increased to 8.8 (95%CI = 1.1-69.9). When the age, the source of androgens, the amount of obesity and the type of obesity were controlled, hyperandrogenemic women had 13.5 (95%CI = 1.1-158.9) odds ratio for elevated SBP. Conclusions: In this study population, the presence of menstrual irregularities are highly predictive for the presence of elevated androgens. Women with elevated androgens have a high risk for obesity, more specifically for central obesity. The androgenemic status is an independent predictor of blood pressure elevation. It is probable that in the general population, the presence of menstrual irregularities are predictive of hyperandrogenemia. There is a great need for a population study of the prevalence of hyperandrogenemia and for longitudinal studies in hyperandrogenemic women (adrenarche to menopause) to investigate the evolution of these relationships. ^

The role of tree size in the leafing phenology of a seasonally dry tropical forest in Belize, Central America

Leafing phenology of two dry-forest sites on soils of different depth (S = shallow, D = deep) at Shipstern Reserve, Belize, were compared at the start of the rainy season (April-June 2000). Trees greater than or equal to 2.5 cm dbh were recorded weekly for 8 wk in three 0.04-ha plots per site. Ten species were analysed individually for their phenological patterns, of which the three most common were Bursera simaruba, Metopium brownei and Jatropha gaumeri. Trees were divided into those in the canopy (> 10 cm dbh) and the subcanopy (less than or equal to 10 cm dbh). Site S had larger trees on average than site D. The proportion of trees flushing leaves at any one time was generally higher in site S than in site D, for both canopy and subcanopy trees. Leaf flush started 2 wk earlier in site S than site D for subcanopy trees, but only 0.5 wk earlier for the canopy trees. Leaf flush duration was 1.5 wk longer in site S than site D. Large trees in the subcanopy flushed leaves earlier than small ones at both sites but in the canopy just at site D. Large trees flushed leaves earlier than small ones in three species and small trees flushed leaves more rapidly in two species. Bursera and Jatropha followed the general trends but Metopium, with larger trees in site D than site S, showed the converse with onset of flushing I wk earlier in site D than site S. Differences in response of the canopy and subcanopy trees on each site can be accounted for by the predominance of spring-flushing or stem-succulent species in site S and a tendency for evergreen species to occur in site D. Early flushing of relatively larger trees in site D most likely requires access to deeper soil water reserves but small and large trees utilize stored tree water in site S.

The impact of environmental enrichment on the outcome variability and scientific validity of laboratory animal studies.

It has been widely accepted for some time that species-appropriate environmental enrichment is important for the welfare of research animals, but its impact on research data initially received little attention. This has now changed, as the use of enrichment as one element of routine husbandry has expanded. In addition to its use in the care of larger research animals, such as nonhuman primates, it is now being used to improve the environments of small research animals, such as rodents, which are used in significantly greater numbers and in a wide variety of studies. Concern has been expressed that enrichment negatively affects both experimental validity and reproducibility. However, when a concise definition of enrichment is used, with a sound understanding of the biology and behaviour of the animal as well as the research constraints, it becomes clear that the welfare of research animals can be enhanced through environmental enrichment without compromising their purpose. Indeed, it is shown that the converse is true: the provision of suitable enrichment enhances the well-being of the animal, thereby refining the animal model and improving the research data. Thus, the argument is made that both the validity and reproducibility of the research are enhanced when proper consideration is given to the research animal's living environment and the animal's opportunities to express species-typical behaviours.

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Birth date predicts alternative life-history pathways in a fish with sequential reproductive tactics

1.In species with plastic expression of alternative reproductive tactics (ARTs), individuals of the same sex, usually males, can adopt different reproductive tactics depending on factors such as body size. 2.The ‘birth date hypothesis’ proposes that condition-dependent expression of ARTs may ultimately depend on birth date, because individuals born at different times of the year may achieve different sizes and express different reproductive tactics accordingly. However, this has rarely been tested. 3.Here, we tested this hypothesis in a fish with ARTs, the peacock blenny (Salaria pavo). A long-term (6 years) mark–recapture study demonstrated that ARTs in the peacock blenny were sequential and that males may follow at least two alternative life-history pathways: a nest-holder pathway, in which males express the nest-holder tactic from their first breeding season onwards, and a parasitic pathway, where males reproduce on their first breeding season as sneaker males and subsequently as nest-holders. 4.We have found evidence of a birth date effect on the expression of ARTs in the peacock blenny. Males following the nest-holder pathway are born earlier and are larger at the first breeding season than males following the parasitic pathway, but they have similar growth curves. 5.The mechanisms underlying a birth date effect are far from clear and might be diverse. We have not found support for a mechanism of body size threshold triggering sexual maturation and subsequent ARTs. A mechanism of tactic determination that is strictly based on timing of first maturation is also unlikely. 6.A proxy of lifetime reproductive success shows crossing (body size associated) fitness curves for the two main life-history pathways.

Case-control study of association of maternal recall of diarrhea or use of antimicrobials in the periconceptional period and neural tube defects

In June 1995 a case-control study was initiated by the Texas Department of Health among Mexican American women residing in the fourteen counties of the Texas-Mexico border. Case-women had carried infants with neural tube defect. Control-women had given birth to infants without neural tube defects. The case-control protocol included a general questionnaire which elicited information regarding illnesses experienced and antibiotics taken from three months prior to conception to three months after conception. An assessment of the associations between periconceptional diarrhea and the risk of neural tube defects indicated that the unadjusted association of diarrhea and risk of neural tube defect was significant (OR = 3.3, CI = 1.4–7.6). The unadjusted association of use of oral antimicrobials and risk of neural tube defect was also significant (OR = 3.4, CI = 1.6–7.3). These associations persisted among women who had no fever during the periconceptional period and were present irrespective of folate intake. Diarrhea was associated with an increased risk of NTD independent of use of antimicrobials. The converse was also true; antimicrobials were associated with an increased risk of NTD independent of diarrhea. Further research regarding these potentially modifiable risk factors is warranted. Replication of these findings could result in interventions in addition to folate supplementation. ^

Théorie des jeux expérimentale & action motrice

How do sportspeople succeed in a non-collaborative game? An illustration of a perverse side effect of altruism Are team sports specialists predisposed to collaboration? The scientific literature on this topic is divided. The present article attempts to end this debate by applying experimental game theory. We constituted three groups of volunteers (all students aged around 20): 25 team sports specialists; 23 individual sports specialists (gymnasts, track & field athletes and swimmers) and a control group of 24 non-sportspeople. Each subgroup was divided into 3 teams that played against each other in turn (and not against teams from other subgroups). The teams played a game based on the well-known Prisoner's Dilemma (Tucker, 1950) - the paradoxical "Bluegill Sunbass Game" (Binmore, 1999) with three Nash equilibria (two suboptimal equilibria with a pure strategy and an optimal equilibrium with a mixed, egotistical strategy (p= 1/2)). This game also features a Harsanyi equilibrium (based on constant compliance with a moral code and altruism by empathy: "do not unto others that which you would not have them do unto you"). How, then, was the game played? Two teams of 8 competed on a handball court. Each team wore a distinctive jersey. The game lasted 15 minutes and the players were allowed to touch the handball ball with their feet or hands. After each goal, each team had to return to its own half of the court. Players were allowed to score in either goal and thus cooperate with their teammates or not, as they saw fit. A goal against the nominally opposing team (a "guardian" strategy, by analogy with the Bluegill Sunbass Game) earned a point for everyone in the team. For an own goal (a "sneaker" strategy), only the scorer earned a point - hence the paradox. If all the members of a team work together to score a goal, everyone is happy (the Harsanyi solution). However, the situation was not balanced in the Nashian sense: each player had a reason to be disloyal to his/her team at the merest opportunity. But if everyone adopts a "sneaker" strategy, the game becomes a free-for-all and the chances of scoring become much slimmer. In a context in which doubt reigns as to the honesty of team members and "legal betrayals", what type of sportsperson will score the most goals? By analogy with the Bluegill Sunbass Game, we recorded direct motor interactions (passes and shots) based on either a "guardian" tactic (i.e. collaboration within the team) or a "sneaker" tactic (shots and passes against the player's designated team). So, was the group of team sports specialist more collaborative than the other two groups? The answer was no. A statistical analysis (difference from chance in a logistic regression) enabled us to draw three conclusions: ?For the team sports specialists, the Nash equilibrium (1950) was stronger than the Harsanyi equilibrium (1977). ?The sporting principles of equilibrium and exclusivity are not appropriate in the Bluegill Sunbass Game and are quickly abandoned by the team sports specialists. The latter are opportunists who focus solely on winning and do well out of it. ?The most altruistic players are the main losers in the Bluegill Sunbass Game: they keep the game alive but contribute to their own defeat. In our experiment, the most altruistic players tended to be the females and the individual sports specialists

Théorie des jeux expérimentale & action motrice

How do sportspeople succeed in a non-collaborative game? An illustration of a perverse side effect of altruism Are team sports specialists predisposed to collaboration? The scientific literature on this topic is divided. The present article attempts to end this debate by applying experimental game theory. We constituted three groups of volunteers (all students aged around 20): 25 team sports specialists; 23 individual sports specialists (gymnasts, track & field athletes and swimmers) and a control group of 24 non-sportspeople. Each subgroup was divided into 3 teams that played against each other in turn (and not against teams from other subgroups). The teams played a game based on the well-known Prisoner's Dilemma (Tucker, 1950) - the paradoxical "Bluegill Sunbass Game" (Binmore, 1999) with three Nash equilibria (two suboptimal equilibria with a pure strategy and an optimal equilibrium with a mixed, egotistical strategy (p= 1/2)). This game also features a Harsanyi equilibrium (based on constant compliance with a moral code and altruism by empathy: "do not unto others that which you would not have them do unto you"). How, then, was the game played? Two teams of 8 competed on a handball court. Each team wore a distinctive jersey. The game lasted 15 minutes and the players were allowed to touch the handball ball with their feet or hands. After each goal, each team had to return to its own half of the court. Players were allowed to score in either goal and thus cooperate with their teammates or not, as they saw fit. A goal against the nominally opposing team (a "guardian" strategy, by analogy with the Bluegill Sunbass Game) earned a point for everyone in the team. For an own goal (a "sneaker" strategy), only the scorer earned a point - hence the paradox. If all the members of a team work together to score a goal, everyone is happy (the Harsanyi solution). However, the situation was not balanced in the Nashian sense: each player had a reason to be disloyal to his/her team at the merest opportunity. But if everyone adopts a "sneaker" strategy, the game becomes a free-for-all and the chances of scoring become much slimmer. In a context in which doubt reigns as to the honesty of team members and "legal betrayals", what type of sportsperson will score the most goals? By analogy with the Bluegill Sunbass Game, we recorded direct motor interactions (passes and shots) based on either a "guardian" tactic (i.e. collaboration within the team) or a "sneaker" tactic (shots and passes against the player's designated team). So, was the group of team sports specialist more collaborative than the other two groups? The answer was no. A statistical analysis (difference from chance in a logistic regression) enabled us to draw three conclusions: ?For the team sports specialists, the Nash equilibrium (1950) was stronger than the Harsanyi equilibrium (1977). ?The sporting principles of equilibrium and exclusivity are not appropriate in the Bluegill Sunbass Game and are quickly abandoned by the team sports specialists. The latter are opportunists who focus solely on winning and do well out of it. ?The most altruistic players are the main losers in the Bluegill Sunbass Game: they keep the game alive but contribute to their own defeat. In our experiment, the most altruistic players tended to be the females and the individual sports specialists

Théorie des jeux expérimentale & action motrice

How do sportspeople succeed in a non-collaborative game? An illustration of a perverse side effect of altruism Are team sports specialists predisposed to collaboration? The scientific literature on this topic is divided. The present article attempts to end this debate by applying experimental game theory. We constituted three groups of volunteers (all students aged around 20): 25 team sports specialists; 23 individual sports specialists (gymnasts, track & field athletes and swimmers) and a control group of 24 non-sportspeople. Each subgroup was divided into 3 teams that played against each other in turn (and not against teams from other subgroups). The teams played a game based on the well-known Prisoner's Dilemma (Tucker, 1950) - the paradoxical "Bluegill Sunbass Game" (Binmore, 1999) with three Nash equilibria (two suboptimal equilibria with a pure strategy and an optimal equilibrium with a mixed, egotistical strategy (p= 1/2)). This game also features a Harsanyi equilibrium (based on constant compliance with a moral code and altruism by empathy: "do not unto others that which you would not have them do unto you"). How, then, was the game played? Two teams of 8 competed on a handball court. Each team wore a distinctive jersey. The game lasted 15 minutes and the players were allowed to touch the handball ball with their feet or hands. After each goal, each team had to return to its own half of the court. Players were allowed to score in either goal and thus cooperate with their teammates or not, as they saw fit. A goal against the nominally opposing team (a "guardian" strategy, by analogy with the Bluegill Sunbass Game) earned a point for everyone in the team. For an own goal (a "sneaker" strategy), only the scorer earned a point - hence the paradox. If all the members of a team work together to score a goal, everyone is happy (the Harsanyi solution). However, the situation was not balanced in the Nashian sense: each player had a reason to be disloyal to his/her team at the merest opportunity. But if everyone adopts a "sneaker" strategy, the game becomes a free-for-all and the chances of scoring become much slimmer. In a context in which doubt reigns as to the honesty of team members and "legal betrayals", what type of sportsperson will score the most goals? By analogy with the Bluegill Sunbass Game, we recorded direct motor interactions (passes and shots) based on either a "guardian" tactic (i.e. collaboration within the team) or a "sneaker" tactic (shots and passes against the player's designated team). So, was the group of team sports specialist more collaborative than the other two groups? The answer was no. A statistical analysis (difference from chance in a logistic regression) enabled us to draw three conclusions: ?For the team sports specialists, the Nash equilibrium (1950) was stronger than the Harsanyi equilibrium (1977). ?The sporting principles of equilibrium and exclusivity are not appropriate in the Bluegill Sunbass Game and are quickly abandoned by the team sports specialists. The latter are opportunists who focus solely on winning and do well out of it. ?The most altruistic players are the main losers in the Bluegill Sunbass Game: they keep the game alive but contribute to their own defeat. In our experiment, the most altruistic players tended to be the females and the individual sports specialists

Seawater carbonate chemistry and biological parameters during experiments with white sea bass Atractoscion nobilis, 2009

A large fraction of the carbon dioxide added to the atmosphere by human activity enters the sea, causing ocean acidification. We show that otoliths (aragonite ear bones) of young fish grown under high CO2 (low pH) conditions are larger than normal, contrary to expectation. We hypothesize that CO2 moves freely through the epithelium around the otoliths in young fish, accelerating otolith growth while the local pH is controlled. This is the converse of the effect commonly reported for structural biominerals.