Calcium in bacteria: a solution to which problem?

Calcium and calcium-binding proteins including those resembling calmodulin are implicated in numerous diverse processes in bacteria. These processes include chemotaxis, sporulation, virulence, the transport of sugars and proteins, phosphorylation, heat shock, the initiation of DNAS replication, septation, nucleoid structure, nuclease activity and recombination, the stability of the envelope, and phospholipids synthesis and configuration. That such varied processes should have a common factor, calcium, suggests major underlying principles of calcium metabolism metabolism which have yet to be discovered.     

Cardiac effects of oxytocin: is there a role for this peptide in cardiovascular homeostasis?

Oxytocin is well known for its role in reproduction. However, evidence has emerged suggesting a role in cardiovascular and hydroelectrolytic homeostasis. Although its renal effects have been characterized, the cardiac ones have not been much studied. Therefore, we aimed to investigate the cardiac effects of oxytocin both in vivo and in vitro. In unanesthetized rats (n=6) intravenous oxytocin (1 mug) decreased dP/dt(max) by 15% (P<0.05) and heart rate by 20% (P<0.001), at the first minute after injection. dP/dt(max) was still lower in OT-treated rats than in controls (n=8) after 15 min (P<0.05), while heart rate returned to control values after 5 min. In isolated hearts, oxytocin was able to promote negative inotropic and chronotropic effects. Perfusion with 10(-5), 10(-6) and 10(-7)M oxytocin resulted in approximately 60% (P<0.01), 25% (P<0.01) and 10% (P<0.05) reduction of left ventricle developed pressure, without effect in lower concentrations (10(-10) to 10(-8) M). Also, dP/dt(max) was reduced by 45 and 20% (10(-5) e 10(-6) M; P<0.01), while diastolic pressure raised and heart rate fell only with 10(-5)M oxytocin (P<0.05). Intravenous oxytocin (1 mug; n=6) increased arterial pressure by 22% at the first minute (+23+/-3 mm Hg; P<0.001), returning to control value thereafter. Thus, oxytocin is able to promote directly negative inotropic and chronotropic effects, but its in vivo effect also involves a reflex mechanism, originated from its pressor effect.     

How silent is the brain: is there a “dark matter” problem in neuroscience?

Evidence from a variety of recording methods suggests that many areas of the brain are far more sparsely active than commonly thought. Here, we review experimental findings pointing to the existence of neurons which fire action potentials rarely or only to very specific stimuli. Because such neurons would be difficult to detect with the most common method of monitoring neural activity in vivo—extracellular electrode recording—they could be referred to as “dark neurons,” in analogy to the astrophysical observation that much of the matter in the universe is undetectable, or dark. In addition to discussing the evidence for largely silent neurons, we review technical advances that will ultimately answer the question: how silent is the brain?     

Minimum viable populations: is there a 'magic number' for conservation practitioners?

Establishing species conservation priorities and recovery goals is often enhanced by extinction risk estimates. The need to set goals, even in data-deficient situations, has prompted researchers to ask whether general guidelines could replace individual estimates of extinction risk. To inform conservation policy, recent studies have revived the concept of the minimum viable population (MVP), the population size required to provide some specified probability of persistence for a given period of time. These studies conclude that long-term persistence requires ≥5000 adult individuals, an MVP threshold that is unaffected by taxonomy, life history or environmental conditions. Here, we re-evaluate this suggestion. We find that neither data nor theory supports its general applicability, raising questions about the utility of MVPs for conservation planning.     

Reappraising the theme of breeding systems in Echinococcus: is outcrossing a rare phenomenon?

Selfing has been considered the most common mode of reproduction in Echinococcus flatworms. However, population genetic studies on the asexual larval stage involving nuclear co-dominant markers have not always revealed significant heterozygote deficiencies--the expected outcome of a regularly and highly inbred population. In this study, we analysed the genetic structure of Echinococcus granulosus sensu lato populations from Southern Brazil during their adult (sexual) stage using 1 mitochondrial and 1 nuclear marker (cox 1 and mdh, respectively). We show that parasite genetic differentiation is largest among definitive hosts (domestic dogs) from different farms, suggesting that transmission is mostly maintained within a farm. Moreover, we show that heterozygote deficiencies are not significant, and we suggest that outbreeding is the most common mode of reproduction of the parasite in that region.     

Resistance to myocardial ischemia in five rat strains: is there a genetic component of cardioprotection?

There is a need to develop new and more consistent animal models of cardioprotection. Traditionally, outbred dogs, rabbits, and rats have been studied. We determined resistance to ischemia in isolated hearts from inbred strains of rats. Hearts from inbred rats: SS/Mcw (Dahl S, Dahl salt-sensitive), DA/Hsd (Dark Agouti), LEW/Hsd (Lewis), and BN/SsN/Mcw (Brown Norway); and from an outbred rat: Hsd:WIST (Wistar) were subjected to 27 min of global, no-flow ischemia, followed by 3 h of reperfusion. Infarct size in the Brown Norway rat was 2.5 times less than that observed in the Dahl S rat, with the Dark Agouti, Lewis, and Wistar rats intermediate in response. Hearts from Brown Norway rats were also most resistant to ischemia in terms of postischemic enzyme leakage and contractile and vascular function compared with other strains. The average polymorphism rate between strains revealed that such strains were genetically diverse. This study demonstrates strain differences in resistance to myocardial ischemia, suggesting these rats could be used to study a genetic and/or environmental basis for these differences and to provide new animal models for the physiological study of cardioprotection.     

Stem cells: is there a future in plastics?

The concept that ostensibly tissue-specific stem cells can give rise to cells of heterologous lineages has gained support from studies using purified hematopoietic stem cells and sensitive donor-cell tracking methods. The ability to exploit these findings in clinical settings will probably depend on new insights into the mechanisms by which such stem cells or their progeny migrate to sites of organ damage and differentiate to cell types competent to participate in tissue regeneration.     

Characterization of the endolysosomal system in human chordoma cell lines: is there a role of lysosomes in chemoresistance of this rare bone tumor?

Chordoma is a rare tumor of the bone derived from remnants of the notochord with pronounced chemoresistance. A common feature of the notochord and chordoma cells is distinct vacuolization. Recently, the notochord vacuole was described as a lysosome-related organelle. Since lysosomes are considered as mediators of drug resistance in cancer, we were interested whether they may also play a role in chemoresistance of chordoma. We characterized the lysosomal compartment in chordoma cell lines by cytochemistry, electron microscopy (ELMI) and mutational analysis of genes essential for the physiology of lysosomes. Furthermore, we tested for the first time the cytotoxicity of chloroquine, which targets lysosomes, on chordoma. Cytochemical stainings clearly demonstrated a huge mass of lysosomes in chordoma cell lines with perinuclear accumulation. Also vacuoles in chordoma cells were positive for the lysosomal marker LAMP1 but showed no acidic pH. Genetic analysis detected no apparent mutation associated with known lysosomal pathologies suggesting that vacuolization and the huge lysosomal mass of chordoma cell lines is rather a relict of the notochord than a result of transformation. ELMI investigation of chordoma cells confirmed the presence of large vacuoles, lysosomes and autophagosomes with heterogeneous ultrastructure embedded in glycogen. Interestingly, chordoma cells seem to mobilize cellular glycogen stores via autophagy. Our first preclinical data suggested no therapeutically benefit of chloroquine for chordoma. Even though, chordoma cells are crammed with lysosomes which are according to their discoverer de Duve “cellular suicide bags”. Destabilizing these “suicide bags” might be a promising strategy for the treatment of chordoma.     

The use of flavonoid aglycones in in vitro systems to test biological activities: based on bioavailability data,is this a valid approach?

The majority of in vitro assays on biological activities of flavonoids have used the aglycone form as the test compound. This form is readily available from commercial sources and comparable approaches have been used for testing efficacy of drugs. This paper presents the hypothesis that aglycones are only transiently present in vivo at significant concentrations at specific sites. The pathway of metabolism of flavonoids in mammals in vivo, focusing on aglycone formation, is examined to facilitate better design in the future of in vitro cell culture experiments. In vitro experiments using flavonoids and cultured cells require careful consideration of absorption and bioavailability for their appropriate interpretation. This revised version was published online in June 2006 with corrections to the Cover Date.     

Selenium concentration in wheat grain: Is there sufficient genotypic variation to use in breeding?

Selenium (Se) is an essential micronutrient for humans and animals, with antioxidant, anti-cancer and anti-viral effects, and wheat is an important dietary source of this element. In this study, surveys of Se concentration in grain of ancestral and wild relatives of wheat, wheat landrace accessions, populations, and commercial cultivars grown in Mexico and Australia were conducted. Cultivars were also grown under the same conditions to assess genotypic variation in Se density. Eleven data sets were reviewed with the aim of assessing the comparative worth of breeding compared with fertilising as a strategy to improve Se intake in human populations. Surveys and field trials that included diverse wheat germplasm as well as other cereals found grain Se concentrations in the range 5–720μgkg⁻¹, but much of this variation was associated with spatial variation in soil selenium. This study detected no significant genotypic variation in grain Se density among modern commercial bread or durum wheat, triticale or barley varieties. However, the diploid wheat, Aegilops tauschii and rye were 42% and 35% higher, respectively, in grain Se concentration than other cereals in separate field trials, and, in a hydroponic trial, rye was 40% higher in foliar Se content than two wheat landraces. While genotypic differences may exist in modern wheat varieties, they are likely to be small in comparison with background soil variation, at least in Australia and Mexico. Field sites that are spatially very uniform in available soil Se would be needed to allow comparison of grain Se concentration and content in order to assess genotypic variation.     

Freshwater fish introductions in mediterranean‐climate regions: are there commonalities in the conservation problem?

Aim To compare patterns and drivers of freshwater fish introductions across five climatically similar regions and evaluate similarities and differences in the non‐native species introduced. Location Five mediterranean‐climate regions: California (USA), central Chile, south‐western Australia, the Iberian peninsula (Spain and Portugal) and the south‐western Cape (South Africa). Methods Species presence–absence for native and non‐native fishes were collated across the regions, and patterns of faunal change were examined using univariate and multivariate statistical approaches. Taxonomic patterns in freshwater fish introductions were evaluated by comparing the number of species introduced by order to the numbers expected from binomial probabilities. Factors influencing multiple introductions of freshwater fish species in mediterranean regions were determined using generalized linear modelling. Results High levels of endemism (70–90%) were revealed for south‐western Cape, south‐western Australia and Chile. Despite their high rates of endemism, all regions currently have more non‐native species than endemic species. Taxonomic selection was found for five orders, although this was only significant for Salmoniformes across regions. The average increase in regional compositional similarity of fish faunas resulting from non‐native fish introductions was 8.0%. Important factors predicting multiple introductions of a species include previous introduction success and mean latitude of its distribution Main conclusions The mediterranean‐climate regions of the world, separated by vast distances, originally had a few fish species in common but are now more similar, owing to species introductions, illustrating the extent and importance of taxonomic homogenization. Introductions are largely driven by taxonomically biased human interests in recreational fisheries, aquaculture and ornamental pet species.     

Activation of development in mammals: is there a role for a sperm cytosolic factor?

In mammalian oocytes, fertilization-associated calcium [Ca2+]i oscillations are responsible for the activation of development. The mechanism(s) by which the sperm triggers the initial [Ca2+]i rise and supports long-lasting oscillations is not resolved. It has been proposed that the sperm may interact with receptors in the oocyte's plasma membrane and engage intracellular signaling pathways that result in Ca2+ release. A different line of investigation suggests that upon sperm-oocyte fusion, a sperm cytosolic factor is released into the oocyte which interacts with unknown cytosolic targets, and generates [Ca2+]i oscillations. We will discuss the most recent evidence for both lines of thought and demonstrate that injections of sperm crude extracts (SF) into mammalian oocytes trigger [Ca2+]i oscillations that support in vitro parthenogenetic development to the blastocyst stage.     

The heritage of Sir William Osler: is there a message to plastic surgeons?

The medical achievements of Sir William Osler (1849-1919), although numerous and important in his time, contribute less to his continued presence in medical literature. What remains is his literary and historical heritage, which is preserved in numerous essays and addresses. Some of his thoughts, which might be worth reading by today's busy plastic surgeons, were chosen from his writings, and they are presented here.