Clonal characterization of the human IgG antibody repertoire to Haemophilus influenzae type b polysaccharide. III. A single VKII gene and one of several JK genes are joined by an invariant arginine to form the most common L chain V region

To characterize the L chain V region repertoire of IgG anti-Haemophilus influenzae type b capsular polysaccharide (Hib-PS) antibodies, clonal antibodies were purified from immune serum and internal amino acid sequences of VKII anti-Hib-PS L chains obtained. We examined VKII L chains because it is the most common VL family expressed in the anti-Hib-PS response. Comparison of VKII amino acid sequences, including the entire CDR2 and CDR3 regions, of five anti-Hib-PS clonal antibodies from four unrelated individuals revealed complete identity with the exception of a single CDR3 residue from one antibody. When the sequence of these antibodies was compared with known VKII genes and myeloma proteins, it was found to be identical to the human VKII gene, A2, whose genomic sequence is presented here. In addition, all five of the VKII anti-Hib-PS antibodies examined contain an arginine inserted at the V-J junction. Finally, in contrast to the extraordinary homology of the VKII-encoded residues, there is variability in the JK gene utilization by these antibodies. These results demonstrate that the most common L chain V region in IgG anti-Hib-PS antibodies is the product of a single germ-line gene. The invariant arginine insertion suggests that this residue has an important role in Ag binding.     

Does observed fertility maximize fitness among New Mexican men?

Our objective is to test an optimality model of human fertility that specifies the behavioral requirements for fitness maximization in order (a) to determine whether current behavior does maximize fitness and, if not, (b) to use the specific nature of the behavioral deviations from fitness maximization towards the development of models of evolved proximate mechanisms that may have maximized fitness in the past but lead to deviations under present conditions. To test the model we use data from a representative sample of 7,107 men living in Albuquerque, New Mexico, between 1990 and 1993. The model we test proposes that low fertility in modern settings maximizes number of grandchildren as a result of a trade-off between parental fertility and next generation fertility. Results do not show the optimization, although the data do reveal a trade-off between parental fertility and offspring education and income. We propose that two characteristics of modern economies have led to a period of sustained fertility reduction and to a corresponding lack of association between income and fertility. The first is the direct link between costs of investment and wage rates due to the forces of supply and demand for labor in competitive economies. The second is the increasing emphasis on cumulative knowledge, skills, and technologies in the production of resources. Together they produce historically novel conditions. These two features of modern economies may interact with evolved psychological and physiological mechanisms governing fertility and parental investment to produce behavior that maximizes the economic productivity of lineages at the expense of fitness. If cognitive processes evolved to track diminishing returns to parental investment and if physiological processes evolved to regulate fertility in response to nutritional state and patterns of breast feeding, we might expect non-adaptive responses when returns from parental investment do not diminish until extremely high levels are reached. With high economic payoffs from parental investment, people have begun to exercise cognitive regulation of fertility through contraception and family planning practices. Those cognitive processes maynot have evolved to handle fitness trade-offs between fertility and parental investment. A preliminary presentation of this data was published in R. I. M. Dunbar, ed.,Human Reproduction Decisions: Biological and Social Perspectives. New York: St. Martin’s Press, 1995. Support for the research project, “Male Fertility and Parenting in New Mexico,” began with two seed grants from the University of New Mexico’s Biomedical Research Grants Program, 1988 and 1989, and one from the University of New Mexico Research Allocations Committee, 1988. Further seed money as well as interim funding came from the William T. Grant Foundation (#89130589 and #91130501). The major support for the project came from the National Science Foundation from 1990 to 1993 (#BNS-9011723 and #DBS-911552). Both National Science Foundation grants included Research Experience for Undergraduates supplements. Hillard S. Kaplan is an Associate Professor of Anthropology at the University of New Mexico. His earlier research and publications focused on food sharing, time allocation, parental investment, and reproductive strategies among Ache hunter-gatherers in Paraguay, Machiguenga and Piro forager-horticulturalists in Peru, and villagers of several ethnicities in Botswana. New research and theory concern fertility, parental investment, and mating strategies in developed and developing nations. This research formulates a new theory of reproductive decision-making and the demographic transition, integrating human capital and parental investment theory in a synthesis of economic and evolutionary approaches. Jane B. Lancaster is a Professor of Anthropology at the University of New Mexico. Her research and publications are on human reproductive biology and behavior, especially human parental investment; women’s reproductive biology of pregnancy, lactation, and child-spacing; and male fertility and investment in children. Current research with Hillard S. Kaplan is on male life history strategies among a large sample of men in New Mexico. She has coedited three books on human parental investment:School-Age Pregnancy and Parenthood (with B. Hamburg),Parenting across the Life Span (with J. Altmann, A. Rossi, and L. Sherrod), andOffspring Abuse and Neglect (with R. Gelles). She is scientific editor of a quarterly journal,Human Nature: An Interdisciplinary, Biosocial Perspective published by Aldine de Gruyter. She is also a council member of the newly formed Human Behavior and Evolution Society. John A. Bock is Andrew W. Mellon Post-Doctoral Fellow in Epidemiology and Population Health at the National Centre for Epidemiology and Population Health, The Australian National University. His research focuses on the allocation of parental investment and the determinants of children’s activities, integrating aspects of economic and evolutionary theory. He has ongoing field research with Bantu and Bushmen agro-pastoralists and forager-horticulturalists in the Okavango Delta, Botswana. He is also collaborating with Lancaster and Kaplan on the determinants of progeny distribution and homosexuality among New Mexican men. Sara E. Johnson is a Ph.D. candidate at the University of New Mexico. Her major research trajectory focuses on trade-offs in life history characters. Her research experience includes participation in a study of variation in growth and development among children in a multi-ethnic community in the Okavango Delta, Botswana, in addition to her dissertation work on individual variation in growth and mortality among juvenile baboons. She is collaborating with Lancaster and Kaplan on the association between survival and fertility among Albuquerque men.     

Phytochrome-mediated effects on extracellular peroxidase activity, lignin content and bending resistance in etiolated Vicia faba epicotyls

Etiolated Vicia faba seedlings were exposed to continuous red light to investigate whether changes in extracellular peroxidase activity were correlated in time and localization with changes in extension growth and/or lignin content in the subapical region of the epicotyl. Continuous red light: (a) increased extracellular peroxidase activity after a lag of ca 0.5 h, followed by a maximum peak after 2.5 h due to slightly acidic isoforms (pI = 6–6.5, according to isoelectrofocusing gels), a minimum after 4 h and a second maximum after 8 h due to acidic isoforms (pI=4–5), (b) increased lignin content and epicotyl resistance to bending after a lag of ca 4 h, i.e. simultaneously with changes in acidic extracellular peroxidase activity, and (c) reduced extension growth to a stable rate after a lag of ca 1 h, not coinciding with the kinetics of any of the extracellular peroxidase isoforms. These effects of continuous red light were at least partially mediated by phytochrome. Tissue printing and anatomical studies revealed red light effects on extracellular peroxidase activity and lignin content mainly in the outer cortical parenchyma. The results are consistent with the involvement of phyto-chrome-mediated effects on extracellular peroxidases (acidic isoforms) in the transduction chain leading to lignin responses to red light.     

The making of the minibody: An engineered β-protein for the display of conformationally constrained peptides

Conformationally constraining selectable peptides onto a suitable scaffold that enables their conformation to be predicted or readily determined by experimental techniques would considerably boost drug discovery process by reducing the gap between the discovery of a peptide lead and the design of a peptidomimetic with a more desirable pharmacological profile. With this in mind, we designed the minibody, a 61-residue β-protein aimed at retaining some desirable features of immunogloblin variable domains, such as tolerance to sequence variability in selected regions of the protein and predictability of main chain conformation of the same regions, based on the ‘canonical structures’ model. To test the ability of the minibody scaffold to support functional sites we also designed a metal binding version of the protein by suitably choosing the sequences of its loops. The minibody was produced both by chemical syntyhesis and expression in E. coli and charactgerized by size exclusion chromatography, UV CD (circular dichroism) spectroscopy and metal binding activity. All our data supported the model, but a more detailed structural characterization of the molecule was impaired by its low soubility. We were able to overcome this problem both by further; mutagenesis of the framework and by addition of a solublizing motif. The minibody is being used to select constrained human IL-6 peptidic ligands from a library displayed on the surface of the f1 bacteriophage.     

Replication of the promiscuous plasmid pLSI: a region encompassing the minus origin of replication is associated with stable plasmid inheritance

Deletion of a region of the promiscuous plasmid pLS1 encompassing the initiation signals for the synthesis of the plasmid lagging strand led to plasmid instability in Streptococcus pneumoniae and Bacillus subtilis. This defect could not be alleviated by increasing the number of copies (measured as double-stranded plasmid DNA) to levels similar to those of the wild-type plasmid pLS1. Our results indicate that in the vicinity of, or associated with the single-stranded origin region of pLS1 there is a plasmid component involved in its stable inheritance. Homology was found between the DNA gyrase binding site within the par region of plasmid pSC101 and the pLS1 specific recombination site RS_R.     

Change in climatically suitable breeding distributions reduces hybridization potential between Vermivora warblers

Aim

Climate change is affecting the distribution of species and subsequent biotic interactions, including hybridization potential. The imperiled Golden-winged Warbler (GWWA) competes and hybridizes with the Blue-winged Warbler (BWWA), which may threaten the persistence of GWWA due to introgression. We examined how climate change is likely to alter the breeding distributions and potential for hybridization between GWWA and BWWA.

Location

North America.

Methods

We used GWWA and BWWA occurrence data to model climatically suitable conditions under historical and future climate scenarios. Models were parameterized with 13 bioclimatic variables and 3 topographic variables. Using ensemble modeling, we estimated historical and modern distributions, as well as a projected distribution under six future climate scenarios. We quantified breeding distribution area, the position of and amount of overlap between GWWA and BWWA distributions under each climate scenario. We summarized the top explanatory variables in our model to predict environmental parameters of the distributions under future climate scenarios relative to historical climate.

Results

GWWA and BWWA distributions are projected to substantially change under future climate scenarios. GWWA are projected to undergo the greatest change; the area of climatically suitable breeding season conditions is expected to shift north to northwest; and range contraction is predicted in five out of six future climate scenarios. Climatically suitable conditions for BWWA decreased in four of the six future climate scenarios, while the distribution is projected to shift east. A reduction in overlapping distributions for GWWA and BWWA is projected under all six future climate scenarios.

Main Conclusions

Climate change is expected to substantially alter the area of climatically suitable conditions for GWWA and BWWA, with the southern portion of the current breeding ranges likely to become climatically unsuitable. However, interactions between BWWA and GWWA are expected to decline with the decrease in overlapping habitat, which may reduce the risk of genetic introgression.     

Eco-evolution from deep time to contemporary dynamics: The role of timescales and rate modulators

Eco-evolutionary dynamics, or eco-evolution for short, are often thought to involve rapid demography (ecology) and equally rapid heritable phenotypic changes (evolution) leading to novel, emergent system behaviours. We argue that this focus on contemporary dynamics is too narrow: Eco-evolution should be extended, first, beyond pure demography to include all environmental dimensions and, second, to include slow eco-evolution which unfolds over thousands or millions of years. This extension allows us to conceptualise biological systems as occupying a two-dimensional time space along axes that capture the speed of ecology and evolution. Using Hutchinson's analogy: Time is the ‘theatre’ in which ecology and evolution are two interacting ‘players’. Eco-evolutionary systems are therefore dynamic: We identify modulators of ecological and evolutionary rates, like temperature or sensitivity to mutation, which can change the speed of ecology and evolution, and hence impact eco-evolution. Environmental change may synchronise the speed of ecology and evolution via these rate modulators, increasing the occurrence of eco-evolution and emergent system behaviours. This represents substantial challenges for prediction, especially in the context of global change. Our perspective attempts to integrate ecology and evolution across disciplines, from gene-regulatory networks to geomorphology and across timescales, from today to deep time.     

Loss of DNA repair mechanisms in cardiac myocytes induce dilated cardiomyopathy

Cardiomyopathy is a progressive disease of the myocardium leading to impaired contractility. Genotoxic cancer therapies are known to be potent drivers of cardiomyopathy, whereas causes of spontaneous disease remain unclear. To test the hypothesis that endogenous genotoxic stress contributes to cardiomyopathy, we deleted the DNA repair gene Ercc1 specifically in striated muscle using a floxed allele of Ercc1 and mice expressing Cre under control of the muscle-specific creatinine kinase (Ckmm) promoter or depleted systemically (Ercc1^−/D mice). Ckmm-Cre^+/−;Ercc1^−/fl mice expired suddenly of heart disease by 7 months of age. As young adults, the hearts of Ckmm-Cre^+/−;Ercc1^−/fl mice were structurally and functionally normal, but by 6-months-of-age, there was significant ventricular dilation, wall thinning, interstitial fibrosis, and systolic dysfunction indicative of dilated cardiomyopathy. Cardiac tissue from the tissue-specific or systemic model showed increased apoptosis and cardiac myocytes from Ckmm-Cre^+/-;Ercc1^−/fl mice were hypersensitive to genotoxins, resulting in apoptosis. p53 levels and target gene expression, including several antioxidants, were increased in cardiac tissue from Ckmm-Cre^+/−;Ercc1^−/fl and Ercc1^−/D mice. Despite this, cardiac tissue from older mutant mice showed evidence of increased oxidative stress. Genetic or pharmacologic inhibition of p53 attenuated apoptosis and improved disease markers. Similarly, overexpression of mitochondrial-targeted catalase improved disease markers. Together, these data support the conclusion that DNA damage produced endogenously can drive cardiac disease and does so mechanistically via chronic activation of p53 and increased oxidative stress, driving cardiac myocyte apoptosis, dilated cardiomyopathy, and sudden death.     

Effects of the egg incubation environment on turtle carapace development

Developing organisms are often exposed to fluctuating environments that destabilize tissue-scale processes and induce abnormal phenotypes. This might be common in species that lay eggs in the external environment and with little parental care, such as many reptiles. In turtles, morphological development has provided striking examples of abnormal phenotypic patterns, though the influence of the environment remains unclear. To this end, we compared fluctuating asymmetry, as a proxy for developmental instability, in turtle hatchlings incubated in controlled laboratory and unstable natural conditions. Wild and laboratory hatchlings featured similar proportions of supernumerary scales (scutes) on the dorsal shell (carapace). Such abnormal scutes likely elevated shape asymmetry, which was highest in natural nests. Moreover, we tested the hypothesis that hot and dry environments cause abnormal scute formation by subjecting eggs to a range of hydric and thermal laboratory incubation regimes. Shape asymmetry was similar in hatchlings incubated at five constant temperatures (26–30°C). A hot (30°C) and severely Dry substrate yielded smaller hatchlings but scutes were not overtly affected. Our study suggests that changing nest environments contribute to fluctuating asymmetry in egg-laying reptiles, while clarifying the conditions at which turtle shell development remains buffered from the external environment.     

Exercise enhancement by RGS14 disruption is mediated by brown adipose tissue

Enhanced exercise capacity is not only a feature of healthful aging, but also a therapy for aging patients and patients with cardiovascular disease. Disruption of the Regulator of G Protein Signaling 14 (RGS14) in mice extends healthful lifespan, mediated by increased brown adipose tissue (BAT). Accordingly, we determined whether RGS14 knockout (KO) mice exhibit enhanced exercise capacity and the role of BAT in mediating exercise capacity. Exercise was performed on a treadmill and exercise capacity was assessed by maximal running distance and work to exhaustion. Exercise capacity was measured in RGS14 KO mice and their wild types (WT), and also in WT mice with BAT transplantation from RGS14 KO mice or from other WT mice. RGS14 KO mice demonstrated 160 ± 9% increased maximal running distance and 154 ± 6% increased work to exhaustion, compared to WT mice. RGS14 KO BAT transplantation to WT mice, resulted in a reversal of phenotype, with the WT mice receiving the BAT transplant from RGS14 KO mice demonstrating 151 ± 5% increased maximal running distance and 158 ± 7% increased work to exhaustion, at three days after BAT transplantation, compared to RGS14 KO donors. BAT transplantation from WT to WT mice also resulted in increased exercise performance, but not at 3 days, but only at 8 weeks after transplantation. The BAT induced enhanced exercise capacity was mediated by (1) mitochondrial biogenesis and SIRT3; (2) antioxidant defense and the MEK/ERK pathway, and increased hindlimb perfusion. Thus, BAT mediates enhanced exercise capacity, a mechanism more powerful with RGS14 disruption.