Phylogenetic analysis of the tribe Bovini using microsatellites

The objective of the present study was to determine if the generally accepted phylogenetic relationships in the tribe Bovini correspond to a phylogenetic scheme derived from polymorphisms at 20 bovine microsatellite loci. This study comprises 17 representative populations: eight Bos taurus, two Bos indicus, one Poëphagus, one Bibos, one Bison, three Bubalus and one Syncerus. Phylogenetic analyses using (δμ)² and chord (D_C) distances revealed substantial divergence among species. Neighbor‐joining trees with both distance measures showed only minor differences. Bos taurus and Bos indicus grouped first, followed by Bos frontalis (Mithan) and Bos grunniens (Yak), Bison bison branched off next and Bubalus bubalis and Syncerus caffer emerged as the two most divergent species from the Bos clade. These findings would suggest that Bos, Poëphagus, and Bibos should be integrated into the Bos genus with each group classified as a subgenus. On the other hand, Bison, Bubalus and Syncerus should each be considered a separate genus. Direct estimates of the divergence times were calculated using the (δμ)² genetic distance. Bos taurus and Bos indicus were estimated to have diverged 0·31–0·82 MYA, Bos and Poëphagus: 0·57–1·53 MYA, Bos and Bibos: 0·57–1·52 MYA, Bos and Bison: 0·46–1·23 MYA, Bos and Bubalus: 1·85–4·93 MYA and Bos and Syncerus: 0·98–2·61 MYA.     

Zinedin, SG2NA, and striatin are calmodulin-binding, WD repeat proteins principally expressed in the brain

Striatin is an intracellular protein characterized by four protein-protein interaction domains, a caveolin-binding motif, a coiled-coil structure, a calmodulin-binding domain, and a WD repeat domain, suggesting that it is a signaling or a scaffold protein. Down-regulation of striatin, which is expressed in a few subsets of neurons, impairs the growth of dendrites as well as rat locomotor activity (Bartoli, M., Ternaux, J. P., Forni, C., Portalier, P., Salin, P., Amalric, M., and Monneron, A. (1999) J. Neurobiol. 40, 234-243). Zinedin, a "novel" protein described here, and SG2NA share with striatin identical protein-protein interaction domains and the same overall domain structure. A phylogenetic analysis supports the hypothesis that they constitute a multigenic family deriving from an ancestral gene. DNA probes and antibodies raised against specific domains of each protein showed that zinedin is mainly expressed in the central nervous system, whereas SG2NA, of more widespread occurrence, is mainly expressed in the brain and muscle. All three proteins are both cytosolic and membrane-bound. All three bind calmodulin in the presence of Ca(2+). In rat brain, SG2NA and striatin are generally not found in the same neurons. Both localize to the soma and dendrites, suggesting that they share a similar type of addressing and closely related functions.     

Body mass and individual fitness in female ungulates: bigger is not always better

In female vertebrates, differences in fitness often correspond to differences in phenotypic quality, suggesting that larger females have greater fitness. Variation in individual fitness can result from variation in life span and/or variation in yearly reproductive success, but no study has yet assessed the relationships between the components of fitness and phenotypic quality while controlling for life span. We tried to fill this gap using data from long-term monitoring (23 years) of marked roe deer and bighorn sheep, two ungulates with very different life histories. In both species, we found a strong positive relationship between an adult female's mass and her probability of reaching old age: over the long term, bigger is indeed better for ungulate females. On the other hand, we found no evidence in either species that heavier females had higher fitness when differences in life span were accounted for: over the short term, bigger is not necessarily better. Our results indicate that, while broad differences in phenotypic quality affect individual fitness, when differences in life span are accounted for phenotypic quality has no residual effect on fitness. Therefore, within a given range of phenotypic quality, bigger is not always better, for reasons which may differ between species.     

Early expression of beta- and gamma-subunits of epithelial sodium channel during human airway development

The amiloride-sensitive epithelial Na(+) channel (ENaC) is an apical membrane protein complex involved in active Na(+) absorption and in control of fluid composition in airways. There are no data reporting the distribution of its pore-forming alpha-, beta-, and gamma-subunits in the developing human lung. With use of two different rabbit polyclonal antisera raised against beta- and gamma-ENaC, immunohistochemical localization of the channel was performed in fetal (10-35 wk) and in adult human airways. Both subunits were detected after 17 wk of gestation on the apical domain of bronchial ciliated cells, in glandular ducts, and in bronchiolar ciliated and Clara cells. After 30 wk, the distribution of beta- and gamma-subunits was similar in fetal and adult airways. In large airways, the two subunits were detected in ciliated cells, in cells lining glandular ducts, and in the serous gland cells. In the distal bronchioles, beta- and gamma-subunits were identified in ciliated and Clara cells. Ultrastructural immunogold labeling confirmed the identification of beta- and gamma-ENaC proteins in submucosal serous cells and bronchiolar Clara cells. Early expression of ENaC proteins in human fetal airways suggests that Na(+) absorption might begin significantly before birth, even if secretion is still dominant.     

Mass- and density-dependent reproductive success and reproductive costs in a capital breeder

For capital breeders, mass may affect reproductive potential. Reproductive expenditure may reduce future reproductive potential, particularly when resources are scarce. To test the hypothesis that reproductive success and the costs of reproduction vary according to mass and population density, we analyzed 25 yr of data on bighorn ewes (Ovis canadensis). The number of adult females was first limited by yearly removals, then allowed to triple. We found no survival costs of reproduction for ewes aged 4-7 yr. For ewes aged 8-14 yr, survival was density dependent for barren ewes but not for ewes that weaned lambs. Failure to lamb was rare and negatively correlated with fertility the following year. At low population density, lactation had a negative effect on mass gain but had a limited reproductive cost. At high density, heavy ewes had higher reproductive success than light ewes, and the reproductive cost and somatic costs of reproduction increased. The cost of reproduction was greater for light than for heavy ewes. Survival of weaned lambs to 1 yr was affected by population density but not by maternal mass or previous reproductive success. In large mammals, manipulations of reproductive effort are problematic, but long-term monitoring of individual mass and reproductive success under varying conditions of resource availability can provide insights into the evolution of life histories.     

Relation between Red Cell Distribution Width and Fibroblast Growth Factor 23 Cleaving in Patients with Chronic Kidney Disease and Heart Failure

Objective

In chronic kidney disease (CKD), both anemia and deregulated phosphate metabolism are common and predictive of adverse outcome. Previous studies suggest that iron status influences phosphate metabolism by modulating proteolytic cleavage of FGF23 into C-terminal fragments. Red cell distribution width (RDW) was recently identified as a strong prognostic determinant for cardiovascular morbidity and mortality, independently of iron status. We assessed whether RDW is associated with FGF23 cleaving in CKD patients with heart failure.

Materials and Methods

The associations between RDW and either intact FGF23 (iFGF23), C-terminal FGF23 (cFGF23, reflecting iFGF23 and C-terminal fragments together) and the iFGF23/cFGF23 ratio were analyzed in 52 patients with CKD (eGFR 34,9 ± 13.9 ml/min/1.73m²) and chronic heart failure (CHF). Associations between RDW and FGF23 forms were studied by linear regression analysis adjusted for parameters of renal function, iron metabolism, phosphate metabolism and inflammation.

Results

Median cFGF23 levels were 197.5 [110–408.5] RU/ml, median iFGF23 levels were 107.3 [65.1–162.2] pg/ml and median FGF23 ratio was 0.80 [0.37–0.86]. Mean RDW was 14.1 ± 1.2%. cFGF23 and RDW were associated (β = 1.63x10^-3, P <0.001), whereas iFGF23 and RDW were not (β = -1.38x10^-3, P = 0.336). The iFGF23/cFGF23 ratio was inversely associated with RDW. The difference between cFGF23 and iFGF23 (cFGF23- iFGF23) was positively associated with RDW (β = 1.74x10^-3, P< 0.001). The association between cFGF23 and RDW persisted upon multivariable linear regression analysis, adjusted for parameters of renal function, phosphate metabolism, iron metabolism and inflammation (β = 0.97x10^-3, P = 0.047).

Conclusion

RDW is associated with cFGF23 but not with iFGF23 levels in patients with CKD and CHF. This suggests a connection between RDW and FGF23 catabolism, independent of iron status and inflammation. Future studies are needed to unravel underlying mechanisms and whether these pertain to the link between RDW and outcome.     

FEMALE PROMISCUITY AND MATERNALLY DEPENDENT OFFSPRING GROWTH RATES IN MAMMALS

Conflicts between family members are expected to influence the duration and intensity of parental care. In mammals, the majority of this care occurs as resource transfer from mothers to offspring during gestation and lactation. Mating systems can have a strong influence on the severity of familial conflict—where female promiscuity is prevalent, conflict is expected to be higher between family members, causing offspring to demand more resources. If offspring are capable of manipulating their mothers and receive resources in proportion to their demands, resource transfer should increase with elevated promiscuity. We tested this prediction, unexplored across mammals, using a comparative approach. The total durations of gestation and lactation were not related to testes mass, a reliable proxy of female promiscuity across taxa. Offspring growth during gestation, however, and weaning mass, were positively correlated with testes mass, suggesting that offspring gain resources from their mothers at faster rates when familial conflict is greater. During gestation, the relationship between offspring growth and testes mass was also related to placenta morphology, with a stronger relationship between testes mass and growth observed in species with a less invasive placenta. Familial conflict could have a pervasive influence on patterns of parental care in mammals.     

Arabidopsis kinetochore fiber-associated MAP65-4 cross-links microtubules and promotes microtubule bundle elongation

The acentrosomal plant mitotic spindle is uniquely structured in that it lacks opposing centrosomes at its poles and is equipped with a connective preprophase band that regulates the spatial framework for spindle orientation and mobility. These features are supported by specialized microtubule-associated proteins and motors. Here, we show that Arabidopsis thaliana MAP65-4, a non-motor microtubule associated protein (MAP) that belongs to the evolutionarily conserved MAP65 family, specifically associates with the forming mitotic spindle during prophase and with the kinetochore fibers from prometaphase to the end of anaphase. In vitro, MAP65-4 induces microtubule (MT) bundling through the formation of cross-bridges between adjacent MTs both in polar and antipolar orientations. The association of MAP65-4 with an MT bundle is concomitant with its elongation. Furthermore, MAP65-4 modulates the MT dynamic instability parameters of individual MTs within a bundle, mainly by decreasing the frequency of catastrophes and increasing the frequency of rescue events, and thereby supports the progressive lengthening of MT bundles over time. These properties are in line with its role of initiating kinetochore fibers during prospindle formation.     

Chemoattraction of macrophages, T lymphocytes, and mast cells is evolutionarily conserved within the human alpha-defensin family

Human defensins are natural peptide antibiotics. On the basis of the position and bonding of six conserved cysteine residues, they are divided into two families, designated alpha- and beta-defensins. Human alpha-defensins are expressed predominantly in neutrophils (human neutrophil peptides (HNP) 1-4) or intestinal Paneth cells (human defensins (HD) 5 and 6). Although alpha-defensins have been implicated in the pathogenesis of inflammatory bowel disease, their immunomodulatory functions are poorly understood. In the present study, HNP-1, HNP-3, and HD5 were found to be potent chemotaxins for macrophages but not dendritic cells using Galphai proteins and MAPK as signal transducers. Alpha-defensins were also chemoattractive for the human mast cell line HMC-1 but lacked, in contrast to beta-defensins, the ability to induce intracellular calcium fluxes. Furthermore, HNP-1, HNP-3, and HD5 comparably mobilized naive as well as memory T lymphocytes. Using the protein kinase C (PKC) inhibitors GF109 and G?6976, we observed a PKC-independent functional desensitization to occur between human alpha-defensins, which suggests a common receptor for HNP-1, HNP-3, and HD5 on immune cells. This alpha-defensin receptor was subject to heterologous desensitization by the PKC activator PMA and to PKC-dependent cross-desensitization by human beta-defensins. Conversely, alpha-defensins desensitized beta-defensin-mediated migration of immune cells in a PKC-dependent manner, suggesting unique receptors for both defensin families. Taken together, our observations indicate that chemoattraction of macrophages, T lymphocytes, and mast cells represents an immunomodulatory function which is evolutionarily conserved within the human alpha-defensin family and tightly regulated by beta-defensins.