Experimental manipulation of food availability leads to short‐term intra‐clutch adjustment in egg mass but not in yolk androgen or thyroid hormones

In birds, mothers can affect their offspring's phenotype and thereby survival via egg composition. It is not well known to what extent and time‐scales environmental variation in resource availability, either via resource constrains or adaptive adjustment to predicted rearing conditions, influences maternal effects. We experimentally studied whether egg and yolk mass and yolk hormone levels respond to short‐term changes in food availability during laying in wild great tits Parus major. Our treatment groups were: 1) food supplementation (mealworms) from the 1st until the last egg; 2) food supplementation from the 1st until the 5th egg, where the effect of cessation of the supplementary food treatment could also be studied; 3) no food supplementation (controls). We analysed both nutritional resources (egg, yolk and albumen mass), and the important developmental signals, yolk androgens (testosterone and androstenedione), and for the first time in a wild population, yolk thyroid hormones (thyroxine and 3,5,3′‐triiodothyronine). Egg mass is a costly resource for females, androgens most likely non‐costly signals, whereas thyroid hormones may be costly signals, requiring environmental iodine. In the food supplemented group egg, yolk and albumen mass increased rapidly relative to controls and when food supplementation was halted, egg and albumen mass decreased, indicating rapid responses to resource availability. Yolk androgen and thyroid hormone levels were not affected by food supplementation during laying. Thyroxine showed an increase over the laying sequence and its biological meaning needs further study. The rapid changes in egg mass to variation in within‐clutch food availability suggest energetic/protein/nutrient constrains on egg formation. The lack of a response in yolk hormones suggest that perhaps in this species the short‐term changes in resource availability during egg laying do not predict offspring rearing conditions, or (for thyroid hormones) do not cause systemic changes in circulating hormones, and hence do not affect maternal signaling.     

The Effect of Antifibrotic Drugs in Rat Precision-Cut Fibrotic Liver Slices

Two important signaling pathways in liver fibrosis are the PDGF- and TGFβ pathway and compounds inhibiting these pathways are currently developed as antifibrotic drugs. Testing antifibrotic drugs requires large numbers of animal experiments with high discomfort. Therefore, a method to study these drugs ex vivo was developed using precision-cut liver slices from fibrotic rat livers (fPCLS), representing an ex vivo model with a multicellular fibrotic environment. We characterized the fibrotic process in fPCLS from rat livers after 3 weeks of bile duct ligation (BDL) during incubation and tested compounds predominantly inhibiting the TGFβ pathway (perindopril, valproic acid, rosmarinic acid, tetrandrine and pirfenidone) and PDGF pathway (imatinib, sorafenib and sunitinib). Gene expression of heat shock protein 47 (Hsp47), α smooth muscle actin (αSma) and pro-collagen 1A1 (Pcol1A1) and protein expression of collagens were determined. During 48 hours of incubation, the fibrosis process continued in control fPCLS as judged by the increased gene expression of the three fibrosis markers, and the protein expression of collagen 1, mature fibrillar collagen and total collagen. Most PDGF-inhibitors and TGFβ-inhibitors significantly inhibited the increase in gene expression of Hsp47, αSma and Pcol1A1. Protein expression of collagen 1 was significantly reduced by all PDGF-inhibitors and TGFβ-inhibitors, while total collagen was decreased by rosmarinic acid and tetrandrine only. However, fibrillar collagen expression was not changed by any of the drugs. In conclusion, rat fPCLS can be used as a functional ex vivo model of established liver fibrosis to test antifibrotic compounds inhibiting the PDGF- and TGFβ signalling pathway.     

DELAYED URIC ACID ACCUMULATION IN PLASMA PROVIDES ADDITIONAL ANTI-OXIDANT PROTECTION AGAINST IRON-TRIGGERED OXIDATIVE STRESS AFTER A WINGATE TEST

Reactive oxygen species are produced during anaerobic exercise mostly by Fe ions released into plasma and endothelial/muscle xanthine oxidase activation that generates uric acid (UA) as the endpoint metabolite. Paradoxically, UA is considered a major antioxidant by virtue of being able to chelate pro-oxidative iron ions. This work aimed to evaluate the relationship between UA and plasma markers of oxidative stress following the exhaustive Wingate test. Plasma samples of 17 male undergraduate students were collected before, 5 and 60 min after maximal anaerobic effort for the measurement of total iron, haem iron, UA, ferric-reducing antioxidant activity in plasma (FRAP), and malondialdehyde (MDA, biomarker of lipoperoxidation). Iron and FRAP showed similar kinetics in plasma, demonstrating an adequate pro-/antioxidant balance immediately after exercise and during the recovery period (5–60 min). Slight variations of haem iron concentrations did not support a relevant contribution of rhabdomyolysis or haemolysis for iron overload following exercise. UA concentration did not vary immediately after exercise but rather increased 29% during the recovery period. Unaltered MDA levels were concomitantly measured. We propose that delayed UA accumulation in plasma is an auxiliary antioxidant response to post-exercise (iron-mediated) oxidative stress, and the high correlation between total UA and FRAP in plasma (R-Square = 0.636; p = 0.00582) supports this hypothesis.     

Handedness in a nonindustrial society challenges the fighting hypothesis as an evolutionary explanation for left-handedness

Handedness is a heritable trait, and left-handedness is related with increased fitness costs. Left-handedness persists, however, as a minority in every human population investigated. One explanation for this persistence has been put forward in the fighting hypothesis, which postulates that left-handers have a frequency-dependent benefit in fights. Support for this has been found in the finding that left-handedness is relatively frequent in populations with high homicide rates, according to estimates of left-handedness partly based on pictures and films made for a different purpose. We measured handedness based on hand preference in 10 ecologically relevant tasks in 621 subjects in the nonindustrial society of the Eipo (Papua, Indonesia) in which homicide rate was very high. This set of tests was validated in 198 Western students. Contrary to the prediction based on the fighting hypothesis, we did not find a high frequency of left-handedness or a difference between men (who participate in warfare) and women (who do not). These findings challenge the idea that fighting is the driving evolutionary force for the persistence of left-handedness in human populations. Furthermore, we found lower percentages of left- and mixed-handers compared to a Western population who executed the same tasks. Since left-handedness is associated with health problems, we suggest that in a society lacking Western health care, selection pressures against left-handedness may be more intense and therefore its frequency may be reduced.     

Towards a noninvasive anatomical and functional diagnostic work-up of patients with suspected coronary artery disease

Combining multidetector computed tomography and cardiovascular magnetic resonance imaging provides the clinician a strategy to comprehensively evaluate coronary morphology and function noninvasively. In the MARCC trial (Magnetic Resonance and CT in suspected CAD) a new noninvasive diagnostic work-up for patients with suspected coronary artery disease will be developed, involving the sequential use of both imaging techniques. (Neth Heart J 2010;18:270-3.)     

A dynamic ubiquitin equilibrium couples proteasomal activity to chromatin remodeling

Protein degradation, chromatin remodeling, and membrane trafficking are critically regulated by ubiquitylation. The presence of several coexisting ubiquitin-dependent processes, each of crucial importance to the cell, is remarkable. This brings up questions on how the usage of this versatile regulator is negotiated between the different cellular processes. During proteotoxic stress, the accumulation of ubiquitylated substrates coincides with the depletion of ubiquitylated histone H2A and chromatin remodeling. We show that this redistribution of ubiquitin during proteotoxic stress is a direct consequence of competition for the limited pool of free ubiquitin. Thus, the ubiquitin cycle couples various ubiquitin-dependent processes because of a rate-limiting pool of free ubiquitin. We propose that this ubiquitin equilibrium may allow cells to sense proteotoxic stress in a genome-wide fashion.     

Fecal corticosteroids in a territorial bird selected for different personalities: daily rhythm and the response to social stress

In this study we tested the hypothesis that in a passerine bird (great tit, Parus major) individuals differing for coping strategies differ in the magnitude of the adrenocortical response to social stress as well. Furthermore, we aimed at characterizing daily rhythms in corticosteroid release before and after social stress. We used 16 males from either of two lines bidirectionally selected for different coping strategies (fast and slow explorers). Social stress was induced by confrontation with an aggressive resident male. Corticosteroid metabolites were analyzed in feces collected at 90-min intervals from 900 to 1630 h on a baseline day, on the day of the social conflict, and on the following day. In both days and in both lines levels varied with time of day in a robust rhythm with a peak in the first sample of the morning and a trough at the end of the light phase. This rhythm correlates with activity (perch hopping). An overall increase in levels relative to baseline day was observed between 30 and 140 min after the challenge. Birds of the less aggressive and more cautious line (slow explorers) showed a trend for a higher response compared to birds of the more aggressive and bolder line (fast explorers), which showed almost no response. On the day after the challenge the birds of the slow line exhibited significantly reduced corticosteroid secretion, probably due to an increased negative feedback. The results provide evidence for a physiological basis of different coping strategies in birds, emerging in response to social stress and with a pattern similar to that in other vertebrates.     

Internal eliminated sequences interrupting the Oxytricha 81 locus: allelic divergence, conservation, conversions, and possible transposon origins

Internal eliminated sequences (IESs) often interrupt ciliate genes in the silent germline nucleus but are exactly excised and eliminated from the developing somatic nucleus from which genes are then expressed. Some long IESs are transposons, supporting the hypothesis that short IESs are ancient transposon relics. In light of that hypothesis and to explore the evolutionary history of a collection of IESs, we have compared various alleles of a particular locus (the 81 locus) of the ciliated protozoa Oxytricha trifallax and O. fallax. Three short IESs that interrupt two genes of the locus are found in alleles from both species, and thus must be relatively ancient, consistent with the hypothesis that short IESs are transposon relics. In contrast, TBE1 transposon interruptions of the locus are allele-specific and probably the results of recent transpositions. These IESs (and the TBE1s) are precisely excised from the DNA of the developing somatic macronucleus. Each IES interrupts a highly conserved sequence. A few nucleotides at the ends of each IES are also conserved, suggesting that they interact critically with IES excision machinery. However, most IES nucleotide positions have evolved at high rates, showing little or no selective constraint for function. Nonetheless, the length of each IES has been maintained (+/- 3 bp). While one IES is approximately 33 bp long, three other IESs have very similar sizes, approximately 70 bp long. Two IESs are surrounded by direct repeats of the sequence TTCTT. No other sequence similarities were found between any of the four IESs. However, the ends of one IES do match the inverted terminal repeat consensus sequence of the "TA" IESs of Paramecium. Three O. trifallax alleles appear to have been recipients in recent conversion events that could have been provoked by double-strand breaks associated with IES ends subsequent to IES transposition. Our findings support the hypothesis that short IESs evolved from ancient transposons that have lost most of their sequences, except those necessary for precise excision during macronuclear development.