Community-level birth rate: a missing link between ecology, evolution and diversity

We propose a conceptual model to explain the variation in species richness in local communities and in build-up of regional species pools over time. The idea is that the opportunity for new species to enter a community (its invasibility) determines the present richness of that community as well as the long-term build-up of a species pool by speciation and migration. We propose that a community's invasibility is determined by the turnover rate of reproductive genets in the community, which we call the 'community-level birth rate'. The faster the turn-over, the more species will accumulate per unit time and per unit community size (number of genets) at a given per-birth rate of immigration and speciation. Spatially discrete communities inhabiting similar environments sum up to metacommunities, whose inhabitant species constitute the regional species pool. We propose that the size of a regional species pool is determined by the aggregate community-level birth rate, the size of the metacommunity through time and age of the metacommunity. Thus, the novel contribution is our proposal of a direct effect of local environment on the build-up rate of species pools. The relative importance of immigrating species and neospecies originating locally will change with the temporal and spatial scale under consideration. We propose that the diversification rate specific to evolutionary lineages and the build-up rate of species pools are two sides of the same coin, and that they are both depending on mean generation time. The proposed model offers a reconciliation of two contrasting paradigms in current community ecology, viz. one focussing on present-time ecological processes and one focussing on historical events governing the size of species pools which in turn determines local richness.     

The missing link between hydrogenosomes and mitochondria

Mitochondria typically respire oxygen and possess a small DNA genome. But among various groups of oxygen-shunning eukaryotes, typical mitochondria are often lacking, organelles called hydrogenosomes being found instead. Like mitochondria, hydrogenosomes are surrounded by a double-membrane, produce ATP and sometimes even have cristae. In contrast to mitochondria, hydrogenosomes produce molecular hydrogen through fermentations, lack cytochromes and usually lack DNA. Hydrogenosomes do not fit into the conceptual mold cast by the classical endosymbiont hypothesis about the nature of mitochondria. Accordingly, ideas about their evolutionary origins have focussed on the differences between the two organelles instead of their commonalities. Are hydrogenosomes fundamentally different from mitochondria, the result of a different endosymbiosis? Or are our concepts about the mitochondrial archetype simply too narrow? A new report has uncovered DNA in the hydrogenosomes of anaerobic ciliates. The sequences show that these hydrogenosomes are, without a doubt, mitochondria in the evolutionary sense, even though they differ from typical mitochondria in various biochemical properties. The new findings are a benchmark for our understanding of hydrogenosome origins.     

FTO and obesity: the missing link

The field of vascular molecular imaging is searching for the "holy grail" of an imaging technique that will quantitatively and reliably assess vulnerable coronary plaques. Fluorescence imaging with indocyanine green specifically identifies lipid-rich plaques in rabbits and in humans and represents a promising, though invasive, approach.     

Embryo quality: the missing link between pregnancy sickness and pregnancy outcome

Pregnancy sickness is widespread yet its etiology is poorly understood. It is almost certainly endocrine in origin and most likely a product of placental hormones, with human chorionic gonadotropin being the strongest candidate. It has long been known that greater levels of nausea and vomiting during pregnancy are associated with a lower incidence of spontaneous abortion, yet the causal mechanisms remain unclear. One current popular explanation is that nausea and vomiting during pregnancy is fetoprotective, inducing aversions to foods, especially meat, dairy and seafoods, which may carry toxins, pathogens or mutagens. However, most spontaneous abortions arise from genetic or epigenetic defects that are present at or near conception. Moreover, measurements of human chorionic gonadotropin (hCG) at the time of implantation, particularly its hyperglycosylated isoform, accurately predict subsequent spontaneous abortion. Thus the developmental fate of most embryos is fixed before the onset of the symptoms of pregnancy sickness. An alternative explanation for the link between pregnancy sickness and spontaneous abortion is the embryo quality hypothesis: high quality embryos are both more likely to produce the biochemical antecedents of pregnancy sickness and avoid spontaneous abortion. Recent work has shown that the link between pregnancy sickness and spontaneous abortion grows stronger with maternal age, dramatically so in mothers 35 or older. This reflects the parallel rise in the incidence of autosomal aneuploidies with maternal age. The link between pregnancy sickness and spontaneous abortion exists not because nausea and vomiting during pregnancy is fetoprotective, but because nausea and vomiting is an index of a high quality embryo. Pregnancy sickness is not adaptive per se, but the result of an antagonistic pleiotropy over thyroid function, where embryos use hCG to modulate maternal thyroid hormone production during gestation. Embryos benefit from the thyroid hormone production that is key to neurodevelopment, but produce maternal nausea and vomiting as a by-product. Pregnancy sickness, however, may still serve to protect embryo quality but by a different mechanism that posited under the MEPH. Embryo quality is protected by calibrating the dietary intake of a micronutrient – iodine – critical to neuromotor development. For most humans over most of our evolutionary history, iodine has been in short supply, and iodine deficiency is still the most common source of cognitive impairment across the globe. Thus it is of interest that the food aversions most commonly associated with pregnancy sickness, to meat, dairy and seafoods, are also the chief dietary sources of iodine. There is a further intriguing property about iodine: both too little and too much during early pregnancy are damaging to embryo brain development. Given that pregnancy sickness is closely linked to iodine intake and thyroid function (hypothyroidism is associated with lower levels of nausea and vomiting, hyperthyroidism with more), an obvious interpretation emerges. The previously described link between diet and pregnancy sickness – pregnancy sickness is less likely when plants and particularly corn/maize are the sole food staples – arises not because plant food staples are safe, as previously suggested, but because these foods are iodine poor and may, in addition, be goitrogenic. Pregnancy sickness, which reduces the dietary intake of iodine, is clearly maladaptive under conditions of iodine deficiency and hypothyroidism. Conversely, higher levels of pregnancy sickness induced by hyperthyroidism may protect embryos from the inimical effects of excessive dietary iodine during early gestation by reducing the intake of iodine rich foods.     

Biotechnology and the Third World: the missing link between research and applications

A United Nations University study investigated the activities of four major United Nations agencies that focussed on helping developing countries gain advanced capabilities in biotechnology. Relevant program and project documents were scrutinized at agency headquarters and managers were interviewed. Then, projects underway in three case countries (Egypt, Thailand, and Venezuela) were examined. The resulting information was used to assess whether United Nations projects were fulfilling these countries' needs and (or) advancing their capabilities in biotechnology. The minute, United Nations originated assistance available was directed solely at increasing capabilities in research and thus benefited bioscientists and their institutes. However, as virtually no linkage exists between the research establishment and the industrial--marketing sector, results from indigenous research does not reach industrialists or health workers. Consequently, biotechnology is neither advancing economic development in the case countries nor helping solve national problems. This situation is likely to persist because corrective systemic changes will be difficult to implement. Major implications of these findings are discussed, particularly as they bear on the United Nations system.     

Dehydroepiandrosterone: the "missing link" between hyperinsulinemia and atherosclerosis?

A well-established epidemiologic association exists between hyperinsulinemia and macrovascular disease. However, the mechanism or mechanisms by which hyperinsulinemia promotes atherogenesis is unknown. Recent evidence indicates that the adrenal steroid dehydroepiandrosterone (DHEA) exerts multiple antiatherogenic effects and also suggests that hyperinsulinemia may reduce serum DHEA and DHEA-sulfate levels by decreasing production and enhancing metabolic clearance. We advance the hypothesis that hyperinsulinemia promotes macrovascular disease in part by reducing serum DHEA and DHEA-sulfate levels and illustrate how this may be the case in two clinical conditions characterized by hyperinsulinemic insulin resistance: aging and obesity.     

Modulation of junctional communication by phosphorylation: protein phosphatases,the missing link in the chain

Protein phosphorylation has been proposed to control the degree of intercellular gap junctional communication at several steps, from gene expression to protein degradation. In vertebrates, gap junctions are composed of proteins from the "connexin" (Cx) gene family, and the majority of connexins are post-translationally modified by phosphorylation. Alterations in the phosphorylation status of proteins, resulting from the dynamic interplay of protein kinases and protein phosphatases, are thought to be involved in a broad variety of connexin processes (such as the trafficking, assembly/disassembly and degradation, as well as the gating of gap junction channels), but the underlying mechanisms remain poorly understood. Although protein kinases have an established role in this process (see Cruciani and Mikalsen, this issue), less is known about the involvement of protein phosphatases. The present review examines the role played by protein dephosphorylation catalysers in the regulation of gap junctional communication.     

The vesicular ATPase: A missing link between acidification and exocytosis

The vesicular adenosine triphosphatase (ATPase) acidifies intracellular compartments, including synaptic vesicles and secretory granules. A controversy about a second function of this ATPase in exocytosis has been fuelled by questions about multiple putative roles of acidification in the exocytic process. Now, Poëa-Guyon et al. (2013. J. Cell Biol. http://dx.doi.org/10.1083/jcb.201303104) present new evidence that the vesicular ATPase performs separate acidification and exocytosis roles and propose a mechanism for how these two functions are causally linked.Vesicular H⁺-ATPases (V-ATPases) function as ATP-driven proton pumps in intracellular compartments, such as endosomes, Golgi-derived vesicles, secretory vesicles, synaptic vesicles, lysosomes, and vacuoles (Forgac, 2007). Acidification is important for a plethora of cell biological processes ranging from endosomal ligand–receptor dissociation to lysosomal degradation (Yan et al., 2009; Williamson et al., 2010; Zoncu et al., 2011). Consequently, interfering with V-ATPase function leads to direct and indirect defects that are difficult to tease apart. In addition, acidification-independent roles of the V-ATPase in secretion and membrane fusion have been proposed (Israël et al., 1986; Peters et al., 2001; Morel et al., 2003; Hiesinger et al., 2005; Liégeois et al., 2006; Sun-Wada et al., 2006; Peri and Nüsslein-Volhard, 2008). The difficulty to distinguish consequences of an acidification-independent mechanism from indirect effects of acidification defects is exacerbated by an unclear dependence of secretion on acidification (Cousin and Nicholls, 1997; Ungermann et al., 1999; Hiesinger et al., 2005).In synaptic vesicles, the V-ATPase generates a proton gradient that is used by an antiporter to fill synaptic vesicles with neurotransmitter. Hence, loss of acidification leads to “empty” synaptic vesicles and loss of neurotransmitter release. Can such vesicles still fuse and thereby “shoot blanks”? The V-ATPase comprises of two sectors that can reversibly dissociate: the cytosolic V1 sector and the membrane-bound V0 sector. Loss of the neuronal a1 subunit of the V0 sector (V0a1) leads to almost complete loss of neurotransmission in Drosophila melanogaster—a phenotype that may result from a defect in neurotransmitter loading or exocytosis (Hiesinger et al., 2005). Single vesicle release events in the V0a1 mutant revealed a quantal postsynaptic response, suggesting that at least some vesicles are loaded. In addition, loss of V0a1 impairs synaptic vesicle cycling in an FM1-43 dye uptake assay, whereas pharmacological block of the V-ATPase with bafilomycin causes no significant defect in this assay (Hiesinger et al., 2005). These findings supported previous studies of an acidification-independent role of the yeast V0 sector and specifically the V0a1 orthologue vph1 in vacuole fusion (Peters et al., 2001; Bayer et al., 2003). They also support earlier controversial implications of the V-ATPase V0 sector in neurotransmitter release (Israël et al., 1986). More recently, numerous studies have added evidence in worm, fish, fly, and mouse for possible acidification-independent roles of various V-ATPase V0 subunits in secretion or membrane fusion (Bayer et al., 2003; Lee et al., 2006; Liégeois et al., 2006; Sun-Wada et al., 2006; Peri and Nüsslein-Volhard, 2008; Di Giovanni et al., 2010; Williamson et al., 2010; Strasser et al., 2011). However, questions about the relationship of V-ATPase–dependent acidification and the observed secretion or membrane fusion defects remained. How can one cleanly separate between two protein functions if one potentially depends on the other? The study of V0a1 has been complicated by the finding that it is not only a synaptic vesicle protein but also localizes to other organelles. Consequently, specific disruption of the acidification function of V0a1 led to endolysosomal acidification defects, even though it partially restored neurotransmission (Williamson et al., 2010). A better dissection of the two possible functions is needed.In this issue of JCB, Poëa-Guyon et al. provide compelling evidence for two separable functions of V0a1 in acidification and exocytosis. Instead of a genetic dissection, they opted for an elegant temporal dissection with the idea that acute inactivation of a function of V0a1 in exocytosis should instantly block neurotransmission, whereas acute inactivation of the proton pump should leave neurotransmission functional as long as loaded vesicles are available. Indeed, Poëa-Guyon et al. (2013) found a fast disruption of secretion in both primary rat neuronal culture and chromaffin cells when they acutely inactivated V0a1 using chromophore-assisted light inactivation. In contrast, inactivation of the reversibly associated V1 sector revealed very different effects than what would be expected from a loss of the proton pump.How about the dependence of exocytosis on acidification? Poëa-Guyon et al. (2013) developed an assay based on granule exocytosis in neurosecretory PC12 cells. Compartmental proton gradients can be abolished by a variety of means, including pharmacological inhibition of the V-ATPase with bafilomycin or concanamycin. A more acute destruction of intracompartmental proton gradients can be achieved through addition of alkalizing ammonium chloride or the potassium ionophore nigericin, which exchanges intracompartmental protons with potassium ions. Interestingly, Poëa-Guyon et al. (2013) found that only the acute disruption of the intracompartmental proton gradients with ammonium chloride or nigericin leads to an impairment of secretion but not block of the V-ATPase. What happens to the V-ATPase and its acidification-independent function under these different conditions? The authors show that both ammonium chloride and nigericin not only abolish the proton gradient but also lead to increased association of the V0 and V1 sectors (Fig. 1). This association is required to form a functional pump. A straightforward explanation for this observation is that the cell attempts to activate the proton pump to reacidify vesicles that lost their proton gradient. In contrast, the pharmacological block of the V-ATPase itself leads to increased free V0 sectors, consistent with loss of proton pump function. In a key experiment, Poëa-Guyon et al. (2013) show that this pharmacological inhibition of the V-ATPase with bafilomycin can override the effects of ammonium chloride or nigericin and restore secretion. If the pharmacological block of the V-ATPase prevents V0–V1 association, no functional pumps assemble even in the presence of ammonium chloride or nigericin. This result implies that the V0–V1 association itself prevents exocytosis. Pharmacological V0–V1 dissociation seems sufficient to expose V0 and exert a V1-independent function in exocytosis. This conclusion is consistent with previous findings in which the same pharmacological inhibition of the V-ATPase was found to leave exocytosis and endocytosis intact (Cousin and Nicholls, 1997; Hiesinger et al., 2005). However, the interpretation of the data changes: according to the new findings, exocytosis does not depend on vesicle acidification, per se, but on V0–V1 association that results from lack of acidification. Acidification and V-ATPase assembly thereby become a checkpoint for vesicle loading, and the assembled V-ATPase becomes a no-go signal for fusion (Fig. 1). The model is elegant and leads Poëa-Guyon et al. (2013) to suggest the V-ATPase as an acidification sensor, similar to previous observations (Hurtado-Lorenzo et al., 2006). However, whether it is really the V-ATPase itself that senses the proton gradient is not directly assessed in this study.Open in a separate windowFigure 1.V-ATPase V0–V1 association blocks secretion. (A) Poëa-Guyon et al. (2013) suggest that dissociation of V0 (red boxes) and V1 (green cylinders) sectors follows vesicle acidification (yellow) and frees the V0 sector for an acute, acidification-independent function in secretion.(B) V-ATPase–independent pharmacological disruption of vesicular acidification causes increased V0–V1 assembly of the functional proton pump, which in turn blocks secretion.(C) Pharmacological disruption of the V-ATPase disrupts both vesicle acidification and V0–V1 assembly, thereby permitting V0-dependent secretion. This mechanism can override disruption of acidification shown in B and restores secretion of nonacidified vesicles.How general is the V-ATPase checkpoint, and what is the mechanism of V0-mediated, acidification-independent exocytosis? Both questions remain unanswered. The checkpoint idea is beautiful and does not obviously contradict current ideas on exocytic regulation. However, potential mechanisms for V0-mediated membrane fusion remain controversial (Saw et al., 2011; Ernstrom et al., 2012). In yeast, V0 proteolipid expansion in the membrane has been proposed to play a direct role in lipid mixing during vacuole fusion based on a thorough genetic dissection of fusion and acidification functions of the V0 sector (Strasser et al., 2011). No such role has hitherto been shown for neurotransmitter release, which comprises numerous different forms of vesicle release that are differentially regulated. A better genetic or pharmacological dissection is needed to reveal when, where, and how V0 meddles with membrane fusion.     

The missing link between neurobiology and behavior in Aplysia conditioning

Over the past decades, a wealth of findings has led to a substantial change in the assumed complexity of classical conditioning. The combined evidence indicates that temporal pairing is neither necessary nor sufficient for the formation of an associative connection. At the same time, studies of model invertebrate nervous systems have allowed us to ask a series of questions about the molecular basis of associative conditioning. The discovery of a pairing-sensitive mechanism in the gill-withdrawal circuitry of Aplysia is regarded as the hallmark of the reductionist approach. This review outlines the insights gathered from behavioral and neurobiological studies. Furthermore, the conceptual frameworks guiding research at the ‘what’ and ‘how’ levels of analysis are compared and contrasted. I argue that a rich cognitive view of conditioning has emerged at the ‘what’ level, whereas the traditional notion of temporal pairing still drives research at the ‘how’ level. A complete account of classical conditioning has to await the resolving of this discordance.     

Mixotrophy: the missing link in consumer-resource-based ecologies

Theoretical Ecology - The classical separate treatments of competition and predation and difficulties in providing a sensible theoretical basis for mutualism attest to the inability of traditional...