Immunity,Transferrin, and Survival in Kwashiorkor

In a study of 40 children with kwashiorkor, serum albumin, transferrin, and immunoglobulin levels were measured. Treatment included chloroquine, pyrimethamine, multivitamins, folic acid, iron compounds, and a high-protein diet. After two weeks the mean serum transferrin values in the children who survived and those who died were 1·30 mg./ml. and 0·33 mg./ml., respectively. Many of the children died immediately after treatment started, and it is suggested that in children with severe kwashiorkor and low serum transferrin levels any increase in free-circulating iron may result in overwhelming infection and death. Thus the appropriate time for instituting iron therapy in such patients should be reconsidered.     

The relationships among sprint performance, voluntary swimming activity, and social dominance in juvenile rainbow trout

The specific objectives of this study were to determine whether sprint performance in juvenile rainbow trout is correlated with either voluntary swimming activity or aggressive behaviors and to determine the reciprocal: the effect of swimming activity and aggression on sprint performance. Sprint performance was assessed by rapidly accelerating trout (5-7-cm fork length) to a fixed velocity (40, 42, or 45 cm s(-1)) and then holding them at that velocity until fatigue. There was considerable interindividual variation in sprint performance not explained by variations in body size, but intraindividual performance was highly repeatable over at least 2 mo. Voluntary swimming was measured as the frequency of transits (voluntary transit activity, VTA) between two identical tanks via a connecting channel with two different flow regimes: zero or minimum velocity (0 or 2.5 cm s(-1)) and high velocity (84 cm s(-1)). There was a strong correlation between sprint performance and VTA in minimal current but no correlation in high current. Furthermore, sprint performance did not predict the outcome of dominance encounters. Experience with rapid acceleration, especially when voluntary, led to a pronounced improvement in sprint performance in proportion to the number of acceleration events. Social dominance encounters had a more complex effect: a significant reduction in sprint performance in previously high-performance sprinters and the reverse for low performers. We propose that there are four independent axes of interindividual variation in juvenile rainbow trout: spontaneous and rheotaxis-stimulated locomotor activity, aggressive activity, and the trainability of sprint performance. The independence of these axes has the potential to produce a much larger diversity in behavioral and ultimately physiological phenotypes than would be produced if the axes were linked.     

Myostatin is a novel tumoral factor that induces cancer cachexia

Humoral and tumoral factors collectively promote cancer-induced skeletal muscle wasting by increasing protein degradation. Although several humoral proteins, namely TNFα (tumour necrosis factor α) and IL (interleukin)-6, have been shown to induce skeletal muscle wasting, there is a lack of information regarding the tumoral factors that contribute to the atrophy of muscle during cancer cachexia. Therefore, in the present study, we have characterized the secretome of C26 colon cancer cells to identify the tumoral factors involved in cancer-induced skeletal muscle wasting. In the present study, we show that myostatin, a procachectic TGFβ (transforming growth factor β) superfamily member, is abundantly secreted by C26 cells. Consistent with myostatin signalling during cachexia, treating differentiated C2C12 myotubes with C26 CM (conditioned medium) resulted in myotubular atrophy due to the up-regulation of muscle-specific E3 ligases, atrogin-1 and MuRF1 (muscle RING-finger protein 1), and enhanced activity of the ubiquitin-proteasome pathway. Furthermore, the C26 CM also activated ActRIIB (activin receptor type?II B)/Smad and NF-κB (nuclear factor κB) signalling, and reduced the activity of the IGF-I (insulin-like growth factor 1)/PI3K (phosphoinositide 3-kinase)/Akt pathway, three salient molecular features of myostatin action in skeletal muscles. Antagonists to myostatin prevented C26 CM-induced wasting in muscle cell cultures, further confirming that tumoral myostatin may be a key contributor in the pathogenesis of cancer cachexia. Finally, we show that treatment with C26 CM induced the autophagy-lysosome pathway and reduced the number of mitochondria in myotubes. These two previously unreported observations were recapitulated in skeletal muscles collected from C26 tumour-bearing mice.     

Linear element-independent meiotic recombination in Schizosaccharomyces pombe

Most organisms form protein-rich, linear, ladder-like structures associated with chromosomes during early meiosis, the synaptonemal complex. In Schizosaccharomyces pombe, linear elements (LinEs) are thread-like, proteinacious chromosome-associated structures that form during early meiosis. LinEs are related to axial elements, the synaptonemal complex precursors of other organisms. Previous studies have led to the suggestion that axial structures are essential to mediate meiotic recombination. Rec10 protein is a major component of S. pombe LinEs and is required for their development. In this report we study recombination in a number of rec10 mutants, one of which (rec10-155) does not form LinEs, but is predicted to encode a truncated Rec10 protein. This mutant has levels of crossing over and gene conversion substantially higher than a rec10 null mutant (rec10-175) and forms cytologically detectable Rad51 foci indicative of meiotic recombination intermediates. These data demonstrate that while Rec10 is required for meiotic recombination, substantial meiotic recombination can occur in rec10 mutants that do not form LinEs, indicating that LinEs per se are not essential for all meiotic recombination.     

Effects of leptin on fetal plasma adrenocorticotropic hormone and cortisol concentrations and the timing of parturition in the sheep

We investigated whether leptin can suppress the prepartum activation of the fetal hypothalamus-pituitary-adrenal (HPA) axis and delay the timing of parturition in the sheep. First, we investigated the effects of a 4-day intravascular infusion of recombinant ovine leptin (n = 7) or saline (n = 6) on fetal plasma adrenocorticotropic hormone (ACTH) and cortisol concentrations, starting from 136 days gestation (i.e., at the onset of the prepartum activation of the fetal HPA axis. The effects of a continuous intrafetal infusion of leptin (n = 7) or saline (n = 5) from 144 days gestation on fetal plasma ACTH and cortisol concentrations and the timing of delivery were also determined in a separate study. There was an increase in fetal plasma ACTH (P < 0.01) and cortisol (P < 0.001) concentrations when saline was infused between 136-137 and 140-141 days gestation. Plasma ACTH and cortisol concentrations did not rise, however, when leptin was infused during this period of gestation. When leptin was infused after 144 days gestation, there was no effect of a 4- to 5-fold increase in circulating leptin on fetal ACTH concentrations. In contrast, leptin infusion from 144 days gestation suppressed (P < 0.05) fetal plasma cortisol concentrations by around 40% between 90 and 42 h before delivery. There was no difference, however, in the length of gestation between the saline- and leptin-infused groups (saline infused, 150.2 +/- 0.5 days; leptin infused, 149.8 +/- 1.0 days). In saline-infused fetuses, there was a significant negative relationship between the plasma concentrations of cortisol (y) and leptin (x) between 138 and 146 days gestation (y = 81.4 - 7.7x, r = 0.38, P < 0.005). This study provides evidence for an endocrine negative feedback loop between leptin and the HPA axis in fetal life.