A role for pore-forming proteins in the pathogenesis by parasites?

Over the past decade or so, pore-forming proteins (PFPs) have been isolated from various immune cells and nonpathogenic bacteria. It is now becoming apparent that PFPs may also be produced by a number of parasites. Although far from definitive, the evidence currently available for the role of PFPs in the survival and pathogenesis by parasites in briefly presented by David Ojcius and John Ding-E Young.     

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.     

Dexamethasone-induced cardioprotection: A role for the phosphatase MKP-1?

AimsPrevious studies suggested that p38 MAPK activation during sustained myocardial ischaemia and reperfusion was harmful. We hypothesize that attenuation of p38MAPK activity via dephosphorylation by the dual-specificity phosphatase MKP-1 should be protective against ischaemia/reperfusion injury. Since the glucocorticoid, dexamethasone, induces the expression of MKP-1, the aim of this study was to determine whether upregulation of this phosphatase by dexamethasone protects the heart against ischaemia/reperfusion injury.Main methodsMale Wistar rats were treated with dexamethasone (3 mg/kg/day ip) for 10 days, before removal of the hearts for Western blot (ip Dex ? P) or perfusion in the working mode (ip Dex + P). Hearts were subjected to 20 min global or 35 min regional ischaemia (36.5 °C) and 30 or 120 min reperfusion. In a separate series, dexamethasone (1 µM) was added to the perfusate for 10 min (Pre + Dex) before or after (Rep + Dex) ischaemia.Key findingsDexamethasone, administered intraperitoneally or added directly to the perfusate, significantly improved post-ischaemic functional recovery and reduced infarct size compared to untreated controls (p < 0.05). These were associated with enhanced up-regulation of MKP-1 protein expression (arbitrary units (mean ± SD): Untreated: 1; ip Dex ? P: 2.59 ± 0.22; ip Dex + P: 1.51 ± 0.22; Pre + Dex: 4.11 ± 0.73, Rep + 15′Dex: 1.51 ± 0.14; untreated vs. all groups, p < 0.05) and attenuation of p38 MAPK activation (p < 0.05) in all dexamethasone-treated groups, except for Rep + 10′Dex. ERK and PKB/Akt activation were unchanged.SignificanceDexamethasone-induced cardioprotection was associated with upregulation of the phosphatase MKP-1 and inactivation of pro-apoptotic p38 MAPK.     

Infertile seeds ofYucca schottii: A beneficial role for the plant in the yucca-yucca moth mutualism?

Summary The yucca-yucca moth interaction is a classic case of obligate mutualism. Female moths pollinate and oviposit in the gynoecium of the flower; however, maturing larvae eat a fraction of the developing seeds. We studied within-fruit distributions of four seed types (fertile, infertile, eaten and uneaten seeds) in order to evaluate costs and benefits in aYucca schottii population in southeastern Arizona. We focused on how the spatial arrangement of seeds affected larval behaviour and, hence, the costs of the mutualism to the yucca. Infertile seeds were distributed throughout both infested and uninfested locules. Additionally, moth larvae feeding in a single locule preferred fertile seeds and even avoided infertile seeds and left the fruit significantly more often when they encountered infertile seeds. We suggest that, regardless of the cause of infertile seeds, they function as blocking units within seed locules and therefore reduce seed predation by moth larvae. We also suggest that, together with certain other fruit traits, the presence of infertile seeds promotes the evolutionary stability of this pollination mutualism.     

Closing the health equity gap: A role for implementation science?

Beryne Odeny discusses strategies to improve equity in health care and health research.

WHO defines health equity as “the absence of unfair and avoidable or remediable differences in health among population groups defined socially, economically, demographically, or geographically or by other means of stratification” [1]. Yet, contrary to this fundamental aspiration and the international mandate on universal health coverage (UHC), almost 50% of the world’s population does not receive needed health services, and progress toward health equity remains elusive [2].     

Mitochondria and aging: A role for the mitochondrial transition pore?

The cellular mechanisms responsible for aging are poorly understood. Aging is considered as a degenerative process induced by the accumulation of cellular lesions leading progressively to organ dysfunction and death. The free radical theory of aging has long been considered the most relevant to explain the mechanisms of aging. As the mitochondrion is an important source of reactive oxygen species (ROS), this organelle is regarded as a key intracellular player in this process and a large amount of data supports the role of mitochondrial ROS production during aging. Thus, mitochondrial ROS, oxidative damage, aging, and aging‐dependent diseases are strongly connected. However, other features of mitochondrial physiology and dysfunction have been recently implicated in the development of the aging process. Here, we examine the potential role of the mitochondrial permeability transition pore (mPTP) in normal aging and in aging‐associated diseases.     

A role for phytotoxins in thePhragmites die-back syndrome?

Die-back and healthy stands ofPhragmites australis (Cav.) Trin. exSteud., in the U.K. and Hungary, were compared in terms of plant morphology and anatomy, sediment redox potential and sulphide levels and plant resistance to internal Poiseuille gas flow. In laboratory experiments rhizome cuttings were exposed to acetic acid or dissolved sulphide in unstirred solution cultures in order to determine whether the die-back symptoms found in the field could be induced by these phytotoxins. Most of the die-back symptoms, namely stunting of adventitious roots and laterals, bud death, callus blockages of the gas-pathways, and vascular blockages (both xylem and phloem), were produced by each of the phytotoxin treatments. These symptoms were largely absent from healthy field sites and from the experimental controls. In a greenhouse experiment, plants were grown in waterlogged sand or loam, with or without a sub-surface organic layer composed of chopped up rhizomes and roots mixed with the soil base. Especially during the first 70 days, redox levels were considerably lowered, and shoot numbers and shoot growth much reduced by the presence of the organic layers; the effects were most pronounced in the sand plus organic matter treatment. It is suggested that accumulated phytotoxins, e.g. orgnaic acids and/or sulphide, whether produced from the death and decay of the plant, or from excessive organic loading or as an indirect results of eutrophication, will perpetuate the die-back ofPhragmites and prevent the recovery of the plant in the short term.     

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.