A role for genetic accommodation in evolution?

Whether evolutionary change can occur by genetic assimilation, or more generally by genetic accommodation, remains controversial. Here we examine some of the experimental evidence for both phenomena. Several experiments in Drosophila suggest that assimilation is possible, and a new paper shows that a color polyphenism in the tobacco hornworm, Manduca sexta, can evolve by genetic accommodation. We argue that genetic accommodation, including assimilation, is a plausible mechanism in evolution; however, more work is required to test how this mechanism acts and how often it is involved in evolutionary change.     

A role for reduced coenzyme Q in atherosclerosis?

Substantial evidence implicates oxidative modification of low density lipoprotein (LDL) as an important event contributing to atherogenesis. As a result, the elucidation of the molecular mechanisms by which LDL is oxidized and how such oxidation is prevented by antioxidants has been a significant research focus. Studies on the antioxidation of LDL lipids have focused primarily on alpha-tocopherol (alpha-TOH), biologically and chemically the most active form of vitamin E and quantitatively the major lipid-soluble antioxidant in extracts prepared from human LDL. In addition to alpha-TOH, plasma LDL also contains low levels of ubiquinol-10 (CoQ10H2; the reduced form of coenzyme Q10). Recent studies have shown that in oxidizing plasma lipoproteins alpha-TOH can exhibit anti- or pro-oxidant activities for the lipoprotein's lipids exposed to a vast array of oxidants. This article reviews the molecular action of alpha-TOH in LDL undergoing "mild" radical-initiated lipid peroxidation, and discusses how small levels of CoQ10H2 can represent an efficient antioxidant defence for lipoprotein lipids. We also comment on the levels alpha-TOH, CoQ10H2 and lipid oxidation products in the intima of patients with coronary artery disease and report on preliminary studies examining the effect of coenzyme Q10 supplementation on atherogenesis in apolipoprotein E knockout mice.     

A role for haemoglobin in all plant roots?

Abstract. We have found haemoglobin in plant roots whereas previously it has been recorded only in nitrogen fixing nodules of plants. Haemoglobin occurs not only in the roots of those plants that are capable of nodulation but also in the roots of species that are not known to nodulate. We suggest that a haemoglobin gene may be a component of the genome of all plants. The gene structure and sequence in two unrelated families of plants suggests that the plant haemoglobins have had a single origin and that this origin relates to the haemoglobin gene of the animal kingdom. At present we cannot completely rule out the possibility of a horizontal transfer of the gene from the animal kingdom to a progenitor of the dicotyledonous angiosperms but we favour a single origin of the gene from a progenitor organism to both the plant and animal kingdoms. We speculate about the possible functions of haemoglobin in plant roots and put the case that it is unlikely to have a function in facilitating oxygen diffusion. We suggest that haemoglobin may act as a signal molecule indicating oxygen deficit and the consequent need to shift plant metabolism from an oxidative to a fermentative pathway of energy generation.     

A role for calcium in Bcl-2 action?

Changes in the cytosolic Ca(2+) concentration ([Ca(2+)](c)) translate a variety of extracellular signals into widely diverse intracellular effects, ranging from secretion to movement, proliferation and also cell death. As regards the last one, it has long been known that large [Ca(2+)](c) increases lead cells to death. More recently, experimental evidence has been obtained that the oncogene Bcl-2 reduces the state of filling of intracellular Ca(2+) stores and thus affects the Ca(2+) responses induced by physiological and pathological stimuli. In this contribution, we will discuss this effect and its significance for the mechanism of action of Bcl-2, an important checkpoint of the apoptotic process.     

A1 toxicity in yeast. A role for Mg?

We have established conditions in which soluble Al is toxic to the yeast Saccharomyces cerevisiae. The major modifications to a standard synthetic medium were lowering the pH and the concentration of Mg ions. Alterations to the PO4, Ca, or K concentration had little effect on toxicity. Organic acids known to chelate Al reduced its toxicity, suggesting that Al3+ is the toxic Al species. The unique ability of Mg ions to ameliorate Al toxicity led us to investigate the hypothesis that Al inhibits Mg uptake by yeast. Yeast cells accumulate Mg, Co, Zn, Ni, and Mn ions via the same transport system (G.F. Fuhrmann, A. Rothstein [1968] Biochim Biophys Acta 163: 325-330). Al3+ inhibited the accumulation of 57Co2+ by yeast cells more effectively than Ga, La, or Mg. In addition, a mutant yeast strain with a defect in divalent cation uptake proved to be more sensitive to Al than a wild-type strain. Taken together, these results suggest that Al may cause Mg deficiency in yeast by blocking Mg transport. We discuss the relevance of yeast as a model for the study of Al toxicity in plant systems.     

A role for cyclic hydroxamates in aluminium resistance in maize?

Hydroxamate siderophores have been found to alleviate Al toxicity in bacteria. In Poaceae plants cyclic hydroxamates, like DIMBOA (2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one) and its derivatives have mostly been studied in relation to either defence against insects or allelopathy. In this study the influence of Al on concentrations of these benzoxazinoids (Bx) in root tips, whole roots and root xylem exudates of Zea mays L. varieties differing in Al resistance was analyzed by HPLC-MS. Aluminium resistant maize variety Sikuani maintained considerably higher Bx levels in root tips than the Al sensitive variety Bakero. In vitro binding of Al to DIMBOA was shown by fluorescence quenching. Addition of DIMBOA to Al-containing nutrient solution protected the sensitive maize against Al toxicity as shown by bioassays using callose and haematoxylin staining of root tips as stress indicators. This is the first study showing that Bx can detoxify Al in solution. Tissue analysis data provide first, circumstantial, support for a role of Bx in defence against Al toxicity also in planta.     

A role for G proteins in plant hormone signalling?

The G protein signalling pathway is one of the most highly conserved mechanisms that enables cells to sense and respond to changes in their environment. Essential components of this are cell surface G protein-coupled receptors (GPCRs) that perceive extracellular ligands, and heterotrimeric G proteins (G proteins) that transduce information from activated GPCRs to down-stream effectors such as enzymes or ion channels. It is now clear from a range of biochemical and molecular studies that some potential G protein signalling components exist in plants. The best examples of these are the seven transmembrane receptor homologue GCR1 and the G_α (GPA1) and G_β (Gβ1) subunit homologues of heterotrimeric G proteins. G protein agonists and antagonists are known to influence a variety of signalling events in plants and have been used to implicate G proteins in a range of signalling pathways that include the plant hormones gibberellin and auxin. Furthermore, antisense suppression of GCR1 expression in Arabidopsis leads to a phenotype that supports a role for this receptor in cytokinin signalling. This review considers the current evidence for and against functional G protein signalling pathways in higher plants and questions whether or not these might be involved in the action of certain plant hormones.     

A therapeutic role for sirtuins in diseases of aging?

The sirtuins are a group of proteins linked to aging, metabolism and stress tolerance in several organisms. Among the many genes that have been shown to affect aging in model organisms, sirtuin genes are unique in that their activity level is positively correlated with lifespan (i.e. they are anti-aging genes). Sirtuins are a druggable class of enzymes (i.e. amenable to intervention by small molecules) that could have beneficial effects on a variety of human diseases. In view of the many functions of Sirtuin 1 (SIRT1) in cells, this review focuses on its role in regulating important aspects of mitochondrial biology. Mitochondria have been linked to aging, and also to diseases of aging. Thus, sirtuins might provide a key link between mitochondrial dysfunction, aging and metabolic disease.     

A role for leptin in sexual maturation and puberty?

Leptin, the ob gene product, is involved in the regulation of body weight in rodents, primates and humans. It provides a molecular basis for the lipostatic theory of the regulation of energy balance. White adipose tissue and placenta are the main sites of leptin synthesis. There is also evidence of ob gene expression in brown fat. Leptin seems to play a key role in the control of body fat stores by coordinated regulation of feeding behaviour, metabolic rate, autonomic nervous system regulation and body energy balance. Apart from the function of leptin in the central nervous system on the regulation of energy balance, it may well be one of the hormonal factors that signal to the brain the body's readiness for sexual maturation and reproduction. During late pregnancy and at birth when maternal fat stores have been developed, leptin levels are high. During these developmental stages leptin could be a messenger molecule signalling the adequacy of the fat stores for reproduction and maintenance of pregnancy. At later stages of gestation leptin could signal the expansion of fat stores in order to prepare the expectant mother for the energy requirements of full-term gestation, labour and lactation. Leptin serum concentrations change during pubertal development in rodents, primates and humans. In girls, leptin serum concentrations increase dramatically as pubertal development proceeds. The pubertal rise in leptin levels parallels the increase in body fat mass. In contrast, leptin levels increase shortly before and during the early stages of puberty in boys and decline thereafter. Testosterone has been found to suppress leptin synthesis by adipocytes both in vivo and in vitro. The decline of leptin levels in late puberty in boys accompanies increased androgen production during that time and most likely reflects suppression of leptin by testosterone and a decrease in fat mass and relative increase in muscle mass during late puberty in males. This overview focuses on those topics of leptin research which are of particular interest in reproductive and adolescent medicine.     

A role for vector-independent transmission in rodent trypanosome infection?

Within host-pathogen systems where vector-borne transmission is the primary route of infection, little or no attention has been paid to the relative importance of secondary or alternative routes of transmission. Here, by contrast, we report the results from a controlled longitudinal field-scale experiment in which the prevalence of fleas (Siphonaptera) was manipulated and the occurrence and distribution of a flea-borne protozoan (Trypanosoma (Herpetosoma) microti) in a natural field vole (Microtus agrestis) population was monitored over a 2-year period. A non-systemic insecticide was applied to individual voles within two treatment grids and the prevalences of fleas and of T. microti were monitored on these and on two control grids. Blood samples were taken from all voles and PCR-based methods used to determine infection status. Insecticidal treatment was highly effective at reducing overall flea prevalence and recaptured animals (treated ca. 4 weeks previously) were very rarely infested (ca. 3%, compared with 50-70+% normally). On the other hand, the probability of trypanosome infection was reduced in treated animals on experimental grids to only around one-third of that normally observed. This suggests that direct, as opposed to flea-borne, transmission may not only occur, it may also be of epidemiological importance. The possibility that the importance of such transmission routes may have been underestimated in ‘vector-borne’ infections more generally is discussed.     

A role for mitochondrial aquaporins in cellular life-and-death decisions?

Mitochondria dominate the process of life-and-death decisions of the cell. Continuous generation of ATP is essential for cell sustenance, but, on the other hand, mitochondria play a central role in the orchestra of events that lead to apoptotic cell death. Changes of mitochondrial volume contribute to the modulation of physiological mitochondrial function, and several ion permeability pathways located in the inner mitochondrial membrane have been implicated in the mediation of physiological swelling-contraction reactions, such as the K+ cycle. However, the channels and transporters involved in these processes have not yet been identified. Osmotic swelling is also one of the fundamental characteristics exhibited by mitochondria in pathological situations, which activates downstream cascades, culminating in apoptosis. The permeability transition pore has long been postulated to be the primary mediator for water movement in mitochondrial swelling during cell death, but its molecular identity remains obscure. Inevitably, accumulating evidence shows that mitochondrial swelling induced by apoptotic stimuli can also occur independently of permeability transition pore activation. Recently, a novel mechanism for osmotic swelling of mitochondria has been described. Aquaporin-8 and -9 channels have been identified in the inner mitochondrial membrane of various tissues, including the kidney, liver, and brain, where they may mediate water transport associated with physiological volume changes, contribute to the transport of metabolic substrates, and/or participate in osmotic swelling induced by apoptotic stimuli. Hence, the recent discovery that aquaporins are expressed in mitochondria opens up new areas of investigation in health and disease.     

A role for skin in Ca metabolism of frogs?

• 1.1. In the leopard frog, Rana pipiens, in vivo Ca loss occurs in similar amounts across the skin and the urine. No change was detected in Ca loss when frogs were injected with either calcitonin or parathyroid hormone. Large doses of 1,25-(OH)₂vitamin D₃ increased urinary Ca loss.
• 2.2. ⁴⁵Ca accumulation across the skin in vivo each day is equivalent to 0.04% of total body Ca or 14% of the total Ca in the extracellular fluids. This accumulation was enhanced by prior adaptation of the frogs to a low Ca pond water.
• 3.3. Unidirectional influx (from 0.2 mM Ca on pond side) was remarkably similar in vitro: 0.56 and in vivo: 0.65 nmol cm⁻² h⁻¹. Based on in vitro measurements, an active transport process does not appear to be involved in this transcutaneous Ca movement.
• 4.4. Substantial deposits of Ca equivalent to five times the total in other “soft” tissues and eleven times that in the total extracellular fluids are found in R. pipiens skin.
• 5.5. Although cutaneous Ca does “turnover” slowly as shown by exchange with external ⁴⁵Ca. the skin Ca concentration does not change with the environmental Ca concentration.
• 6.6. Possible role(s) of cutaneous Ca in frogs' overall Ca metabolism are discussed.