The onchocerciasis chronicle: from the beginning to the end?

The year 2012 marks the 25th anniversary of the donation of ivermectin to fight onchocerciasis and the projected date for elimination of transmission of the disease in the Americas. This review looks at the history of onchocerciasis, from its discovery through to 2025, by which time it is projected that the disease will have been eliminated as a public health problem, except in a handful of sub-Saharan countries, where it should be well on the way towards elimination.     

Articulations of Islamophobia: from the extreme to the mainstream?

This article will examine the construction and functions of, as well as relationship between, the diverse and changing articulations of Islamophobia. The aim is to contribute to debates about the definition of Islamophobia, which have tended to be contextually specific, fixed and/or polarized between racism and religious prejudice, between extreme and mainstream, state and non-state versions or undifferentiated, and offer a more nuanced framework to: (a) delineate articulations of Islamophobia as opposed to precise types and categories; (b) highlight the porosity in the discourse between extreme articulations widely condemned in the mainstream, and normalized and insidious ones, which the former tend to render more acceptable in comparison; (c) map where these intersect in response to events, historical and political conditions and new ideological forces and imperatives and (d) compare these articulations of Islamophobia in two contexts, France and the US.     

Xenotransplantation: from animal facility to the clinic?

Since 1960, clinical organ transplantation has evolved from an experimental procedure to highly successful ‘routine’, but as technical advances have extended eligibility to more victims of end-stage organ disease, the supply of donor organs has lagged behind. Urgency of need, probability of success and ability to pay are often used to limit waiting lists; without these, as many as 124 000 transplants per year could be performed in the USA alone. Although the supply of organs from human donors may well be assisted in future by increased public education and changes in donor laws, it is unlikely that the need for organs will ever be met by generosity and calamity alone — hence the enthusiasm for other sources of organs.     

Membrane Delivery to the Yeast Autophagosome from the Golgi�CEndosomal System

While many of the proteins required for autophagy have been identified, the source of the membrane of the autophagosome is still unresolved with the endoplasmic reticulum (ER), endosomes, and mitochondria all having been evoked. The integral membrane protein Atg9 is delivered to the autophagosome during starvation and in the related cytoplasm-to-vacuole (Cvt) pathway that occurs constitutively in yeast. We have examined the requirements for delivery of Atg9-containing membrane to the yeast autophagosome. Atg9 does not appear to originate from mitochondria, and Atg9 cannot reach the forming autophagosome directly from the ER or early Golgi. Components of traffic between Golgi and endosomes are known to be required for the Cvt pathway but do not appear required for autophagy in starved cells. However, we find that pairwise combinations of mutations in Golgi-endosomal traffic components apparently only required for the Cvt pathway can cause profound defects in Atg9 delivery and autophagy in starved cells. Thus it appears that membrane that contains Atg9 is delivered to the autophagosome from the Golgi-endosomal system rather than from the ER or mitochondria. This is underestimated by examination of single mutants, providing a possible explanation for discrepancies between yeast and mammalian studies on Atg9 localization and autophagosome formation.     

Multi-element isotope fractionation concepts to characterize the biodegradation of hydrocarbons — from enzymes to the environment

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Mechanotransduction from the ECM to the genome: Are the pieces now in place?

A multitude of biochemical signaling processes have been characterized that affect gene expression and cellular activity. However, living cells often need to integrate biochemical signals with mechanical information from their microenvironment as they respond. In fact, the signals received by shape alone can dictate cell fate. This mechanotrasduction of information is powerful, eliciting proliferation, differentiation, or apoptosis in a manner dependent upon the extent of physical deformation. The cells internal "prestressed" structure and its "hardwired" interaction with the extra-cellular matrix (ECM) appear to confer this ability to filter biochemical signals and decide between divergent cell functions influenced by the nature of signals from the mechanical environment. In some instances mechanical signaling through the tissue microenvironment has been shown to be dominant over genomic defects, imparting a normal phenotype on cells that otherwise have transforming genetic lesions. This mechanical control of phenotype is postulated to have a central role in embryogenesis, tissue physiology as well as the pathology of a wide variety of diseases, including cancer. We will briefly review studies showing physical continuity between the external cellular microenvironment and the interior of the cell nucleus. Newly characterized structures, termed nuclear envelope lamina spanning complexes (NELSC), and their interactions will be described as part of a model for mechanical transduction of extracellular cues from the ECM to the genome.     

Where is the right path heading from the centromere to spindle microtubules?

The kinetochore is a large protein complex that ensures accurate chromosome segregation during mitosis by connecting the centromere and spindle microtubules. One of the kinetochore sub-complexes, the constitutive centromere-associated network (CCAN), associates with the centromere and recruits another sub-complex, the KMN (KNL1, Mis12, and Ndc80 complexes) network (KMN), which binds to spindle microtubules. The CCAN-KMN interaction is mediated by two parallel pathways (CENP-C- and CENP-T-pathways) in the kinetochore, which bridge the centromere and microtubules. Here, we discuss dynamic protein-interaction changes in the two pathways that couple the centromere with spindle microtubules during mitotic progression.     

What ecological factors favor the shift from distyly to homostyly? A study from the perspective of reproductive assurance

Aims Distyly is one of the most widespread floral polymorphisms promoting cross-fertilization. Evolutionary transition from obligate cross-fertilized distyly to predominantly self-fertilized homostyly is frequently documented in various groups. However, empirical studies concerning the ecological factors connected with this transition are still lacking. Primula chungensis, suggested to be evolving from distyly to homostyly, provides an ideal model for the study of the ecological factors concerned with this transition. We study P. chungensis to understand if autonomous self-fertilization would provide reproductive assurance for the self-fertilized homo-styled morph in the field.Methods The incompatibility features of P. chungensis were tested with hand-pollination experiments. We compared the capacity of autonomous self-fertilization between the distylous and homo-styled morph of P. chungensis in the field by excluding the pollinators with bags. In addition, the degrees of herkogamy of some P. chungensis plants were between the short-styled and homo-styled morphs. These plants were studied to understand whether they were able to obtain greater reproductive assurance when the herkogamy in the flowers was reduced.Important findings All three morphs of P. chungensis were highly self- and intra-morph compatible. The degree of herkogamy positively correlated with the capacity for autonomous self-fertilization. A negative correlation between the degree of herkogamy and the magnitude of pollen limitation was found, but no significant correlation was found between the degree of herkogamy and the contribution of cross-fertilization to overall fertilization. This study suggests that reducing the degree of herkogamy can significantly increase the reproductive assurance for a self-compatible plant. Our results provided evidence that the homo-styled morph of P. chungensis had the highest capacity for autonomous self-fertilization and the highest seed production in the field, because autonomous self-fertilization provided reproductive assurance for the homo-styled morph. This may cause selection towards the transition from distyly to homostyly.     

What to expect from MRI in the investigation of the central nervous system?

Functional magnetic resonance imaging (fMRI) has appeared as a new tool that is very powerful for cognitive neuroscience, offering the potential to look at the dynamics of cerebral processes underlying cognition, non-invasively and on an individual basis. Work remains to be done to optimize the technique and to better understand its basic mechanisms, but one may expect to build in a foreseeable future a functional list of the main brain cortical networks implicated in sensory-motor or cognitive processes. Still, the real understanding of brain function requires direct access to the functional unit consisting of the neuron, so that one may look at the transient temporal relationships that exist between largely distributed groups of hundreds or thousands of neurons. Furthermore, communication pathways between networks, which are carried by brain white matter, must be identified to establish connectivity maps at the individual scale, taking into account individual variability resulting from genetic factors and cerebral plasticity. In this respect, MRI of molecular diffusion is very sensitive to water molecular motion and, thus, to tissue dynamic microstructure, such as cell size and geometry. Preliminary data suggest that diffusion MRI visualizes dynamic tissue changes associated with large neuronal activation and space orientation of large bundles of myelinated axons in the white matter.     

Is the signal from the mesophyll to the guard cells a vapour‐phase ion?

Previous studies have suggested that the red light and CO₂ responses of stomata are caused by a signal from the mesophyll to the guard cells. Experiments were conducted to test the idea that this signal is a vapour‐phase ion. Stomata in isolated epidermes of Tradescantia pallida were found to respond to air ions created by an electrode that was positioned under the epidermes. Anthocyanins in the epidermes of this species were observed to change colour in response to these air ions, and this change in colour was attributed to changes in pH. A similar change in lower epidermal colour was observed in intact leaves upon illumination and with changes in CO₂ concentration. Based on the change in epidermal colour, the pH of the epidermis was estimated to be approximately 7.0 in darkness and 6.5 in the light. Stomata in isolated epidermes responded to pH when suspended over (but not in contact with) solutions of different pH. We speculate that stomatal responses to CO₂ and light are caused by vapour‐phase ions, possibly hydronium ions that change the pH of the epidermis.     

Tailoring the switch from IRES-dependent to 5′-end-dependent translation with the RNase P ribozyme

Translation initiation driven by internal ribosome entry site (IRES) elements is dependent on the structural organization of the IRES region. We have previously shown that a structural motif within the foot-and-mouth-disease virus IRES is recognized in vitro as substrate for the Synechocystis sp. RNase P ribozyme. Here we show that this structure-dependent endonuclease recognizes the IRES element in cultured cells, leading to inhibition of translation. Inhibition of IRES activity was dependent on the expression of the active ribozyme RNA subunit. Moreover, expression of the antisense sequence of the ribozyme did not inhibit IRES activity, demonstrating that stable RNA structures located upstream of the IRES element do not interfere with internal initiation. RNAs carrying defective IRES mutants that were substrates of the ribozyme in vivo revealed an increased translation of the reporter in response to the expression of the active ribozyme. In support of RNA cleavage, subsequent analysis of the translation initiation manner indicated a switch from IRES-dependent to 5′-end-dependent translation of RNase P target RNAs. We conclude that the IRES element is inactivated by expression in cis of RNase P in the cytoplasm of cultured cells, providing a promising antiviral tool to combat picornavirus infections. Furthermore, our results reinforce the essential role of the structural motif that serves as RNase P recognition motif for IRES activity.     

Biogas from Macroalgae: is it time to revisit the idea?

The economic and environmental viability of dedicated terrestrial energy crops is in doubt. The production of large scale biomass (macroalgae) for biofuels in the marine environment was first tested in the late 1960’s. The culture attempts failed due to the engineering challenges of farming offshore. However the energy conversion via anaerobic digestion was successful as the biochemical composition of macroalgae makes it an ideal feedstock. The technology for the mass production of macroalgae has developed principally in China and Asia over the last 50 years to such a degree that it is now the single largest product of aquaculture. There has also been significant technology transfer and macroalgal cultivation is now well tried and tested in Europe and America. The inherent advantage of production of biofuel feedstock in the marine environment is that it does not compete with food production for land or fresh water. Here we revisit the idea of the large scale cultivation of macroalgae at sea for subsequent anaerobic digestion to produce biogas as a source of renewable energy, using a European case study as an example.     

Do testosterone declines during the transition to marriage and fatherhood relate to men's sexual behavior? Evidence from the Philippines

Testosterone (T) is thought to help facilitate trade-offs between mating and parenting in humans. Across diverse cultural settings married men and fathers have lower T than other men and couples' sexual activity often declines during the first years of marriage and after having children. It is unknown whether these behavioral and hormonal changes are related. Here we use longitudinal data from a large study in the Philippines (n = 433) to test this model. We show that among unmarried non-fathers at baseline (n = 153; age: 21.5 ± 0.3 years) who became newly married new fathers by follow-up (4.5 years later), those who experienced less pronounced longitudinal declines in T reported more frequent intercourse with their partners at follow-up (p < 0.01) compared to men with larger declines in T. Controlling for duration of marriage, findings were similar for men transitioning from unmarried to married (without children) (p < 0.05). Men who remained unmarried and childless throughout the study period did not show similar T-sexual activity outcomes. Among newly married new fathers, subjects who had frequent intercourse both before and after the transition to married fatherhood had more modest declines in T compared to peers who had less frequent sex (p < 0.001). Our findings are generally consistent with theoretical expectations and cross-species empirical observations regarding the role of T in male life history trade-offs, particularly in species with bi-parental care, and add to evidence that T and sexual activity have bidirectional relationships in human males.     

Microbes inside—from diversity to function: the case of Akkermansia

The human intestinal tract is colonized by a myriad of microbes that have developed intimate interactions with the host. In healthy individuals, this complex ecosystem remains stable and resilient to stressors. There is significant attention on the understanding of the composition and function of this intestinal microbiota in health and disease. Current developments in metaomics and systems biology approaches allow to probe the functional potential and activity of the intestinal microbiota. However, all these approaches inherently suffer from the fact that the information on macromolecules (DNA, RNA and protein) is collected at the ecosystem level. Similarly, all physiological and other information collected from isolated strains relates to pure cultures grown in vitro or in gnotobiotic systems. It is essential to integrate these two worlds of predominantly chemistry and biology by linking the molecules to the cells. Here, we will address the integration of omics- and culture-based approaches with the complexity of the human intestinal microbiota in mind and the mucus-degrading bacteria Akkermansia spp. as a paradigm.     

The Rice α-Amylase Glycoprotein Is Targeted from the Golgi Apparatus through the Secretory Pathway to the Plastids

The well-characterized secretory glycoprotein, rice (Oryza sativa) α-amylase isoform I-1 (AmyI-1), was localized within the plastids and proved to be involved in the degradation of starch granules in the organelles of rice cells. In addition, a large portion of transiently expressed AmyI-1 fused to green fluorescent protein (AmyI-1-GFP) colocalized with a simultaneously expressed fluorescent plastid marker in onion (Allium cepa) epidermal cells. The plastid targeting of AmyI-1 was inhibited by both dominant-negative and constitutively active mutants of Arabidopsis thaliana ARF1 and Arabidopsis SAR1, which arrest endoplasmic reticulum-to-Golgi traffic. In cells expressing fluorescent trans-Golgi and plastid markers, these fluorescent markers frequently colocalized when coexpressed with AmyI-1. Three-dimensional time-lapse imaging and electron microscopy of high-pressure frozen/freeze-substituted cells demonstrated that contact of the Golgi-derived membrane vesicles with cargo and subsequent absorption into plastids occur within the cells. The transient expression of a series of C-terminal-truncated AmyI-1-GFP fusion proteins in the onion cell system showed that the region from Trp-301 to Gln-369 is necessary for plastid targeting of AmyI-1. Furthermore, the results obtained by site-directed mutations of Trp-302 and Gly-354, located on the surface and on opposite sides of the AmyI-1 protein, suggest that multiple surface regions are necessary for plastid targeting. Thus, Golgi-to-plastid traffic appears to be involved in the transport of glycoproteins to plastids and plastid targeting seems to be accomplished in a sorting signal–dependent manner.     

Has the transition to agriculture reshaped the demographic structure of prehistoric populations? New evidence from the Levant

This paper presents the demographic changes that followed the transition from a hunting-gathering way of life (Natufian) to an agricultural, food-producing economy (Neolithic) in the southern Levant. The study is based on 217 Natufian (10,500-8,300 BC) skeletons and 262 Neolithic (8,300-5,500 BC) skeletons. Age and sex identification were carried out, and life tables were constructed. A five-parameter competing hazard model developed by Siler ([1979] Ecology 60:750-757) was used to smooth life-table data. No indication of increased mortality with the advent of agriculture was noted. On the contrary, both life expectancy at birth (24.6 vs. 25.5 years) and adults' mean age at death (31.2 vs. 32.1 years) increased slightly from the Natufian to the Neolithic period (assuming stationary populations). Yet the transition to agriculture affected males and females differently: mean age at death in the Natufian was higher for adult females compared to adult males, while in the Neolithic, it was the reverse. One interpretation given to the distribution of female ages at death is that with the onset of the Neolithic period, maternal mortality increased as a result of a concomitant increase in fertility. If the adoption of agriculture in the Levant increased the rate of population growth at the beginning of the Neolithic, expectation of life may have increased dramatically.     

Aspects on the integrative actions of the brain from neural networks to “brain-body medicine”

“Integration” is a key term in describing how nervous system can perform high level functions. A first condition to have “integration” is obviously the presence of efficient “communication processes” among the parts that have to be combined into the harmonious whole. In this respect, two types of communication processes, called wiring transmission (WT) and volume transmission (VT), respectively, were found to play a major role in the nervous system, allowing the exchange of signals not only between neurons, but rather among all cell types present in the central nervous system (CNS). A second fundamental aspect of a communication process is obviously the recognition/decoding process at target level. As far as this point is concerned, increasing evidence emphasizes the importance of supramolecular complexes of receptors (the so called receptor mosaics) generated by direct receptor–receptor interactions. Their assemblage would allow a first integration of the incoming information already at the plasma membrane level. Recently, evidence of two new subtypes of WT and VT has been obtained, namely the tunnelling nanotubes mediated WT and the microvesicle (in particular exosomes) mediated VT allowing the horizontal transfer of bioactive molecules, including receptors, RNAs and micro-RNAs. The physiological and pathological implications of these types of communication have opened up a new field that is largely still unexplored. In fact, likely unsuspected integrative actions of the nervous system could occur. In this context, a holistic approach to the brain-body complex as an indissoluble system has been proposed. Thus, the hypothesis has been introduced on the existence of a brain-body integrative structure formed by the “area postrema/nucleus tractus solitarius” (AP/NTS) and the “anteroventral third ventricle region/basal hypothalamus with the median eminence” (AV3V-BH). These highly interconnected regions operate as specialized interfaces between the brain and the body integrating brain-borne and body-borne neural and humoral signals.     

What Was the Real Contribution of Endosymbionts to the Eukaryotic Nucleus? Insights from Photosynthetic Eukaryotes

Eukaryotic genomes are composed of genes of different evolutionary origins. This is especially true in the case of photosynthetic eukaryotes, which, in addition to typical eukaryotic genes and genes of mitochondrial origin, also contain genes coming from the primary plastids and, in the case of secondary photosynthetic eukaryotes, many genes provided by the nuclei of red or green algal endosymbionts. Phylogenomic analyses have been applied to detect those genes and, in some cases, have led to proposing the existence of cryptic, no longer visible endosymbionts. However, detecting them is a very difficult task because, most often, those genes were acquired a long time ago and their phylogenetic signal has been heavily erased. We revisit here two examples, the putative cryptic endosymbiosis of green algae in diatoms and chromerids and of Chlamydiae in the first photosynthetic eukaryotes. We show that the evidence sustaining them has been largely overestimated, and we insist on the necessity of careful, accurate phylogenetic analyses to obtain reliable results.Today it is widely accepted that photosynthesis originated in eukaryotes by the endosymbiosis of a cyanobacterium within a heterotrophic eukaryotic host. This occurred in a lineage that subsequently diversified to give rise to the three contemporary groups of primary photosynthetic eukaryotes: Viridiplantae (including green algae and land plants), Rhodophyta and Glaucophyta, grouped collectively within a unique eukaryotic superphylum called Archaeplastida (Adl et al. 2005) or Plantae (Cavalier-Smith 1982). Recently, a second case of primary endosymbioses has been unveiled thanks to the characterization of Paulinella chromatophora, a filose amoeba that hosts a cyanobacterium with a reduced genome that has been described as “a plastid in the making” (Marin et al. 2005; Keeling and Archibald 2008; Nowack et al. 2008). Primary endosymbioses resulted in the establishment of plastids with two membranes. However, a vast variety of eukaryotes possess plastids with three or more membranes. They derive from the endosymbioses of primary photosynthetic eukaryotes within other eukaryotic cells (Delwiche 1999; Keeling 2013). Such secondary endosymbioses have spread photosynthesis across the eukaryotic tree, either by the endosymbiosis of red or of green algae. Whereas it is almost certain that secondary endosymbioses of green algae occurred twice (in euglenids and chlorarachniophytes), secondary red algal plastids are found in a variety of alveolates, stramenopiles, cryptophytes, and haptophytes, and the number of red algal endosymbioses at the origin of these groups has been matter of intense debate (Baurain et al. 2010; Keeling 2010, 2013; Burki et al. 2012b). Moreover, the existence of tertiary endosymbioses (namely, the symbiosis of a secondary photosynthetic eukaryote within another eukaryotic cell) and of plastid replacements makes the picture of plastid evolution in eukaryotes even more complex. Dinoflagellates, some of which have replaced their ancestral red algal plastids by green algae, diatoms, haptophytes, or cryptophytes, are paradigmatic examples of such complex situations (Keeling 2013).The evolution of plastids has been studied using genes from the plastid genome as well as typical eukaryotic nuclear genes, which allow inferring the phylogenies of both the plastids and their hosts. The use of those markers has led to interesting discoveries, such as the monophyly of the Archaeplastida (Moreira et al. 2000; Rodríguez-Ezpeleta et al. 2005) or the difficulties in reconciling the plastid and host histories in eukaryotes with red algal plastids (Baurain et al. 2010; Burki et al. 2012b). However, a third class of genes can also provide useful complementary information: the genes of plastid origin retrieved within the nuclear genome of the host. In fact, contemporary plastids have small genomes, which is due to the fact that most of the original cyanobacterial symbiont genes were lost or transferred to the host nucleus (by a process called endosymbiotic gene transfer, EGT) during the evolution of plastids (Weeden 1981; Martin et al. 1998). These transfer events are not restricted to plastid endosymbioses—the same phenomenon occurred during the endosymbiosis that gave rise to the mitochondria (Gray et al. 1999; Burger et al. 2003).EGT genes may serve to study the evolutionary history of plastids and, in particular, the presence of cryptic endosymbioses. In fact, species that had a plastid in the past but lost photosynthesis may have conserved genes of plastid origin in their nuclear genomes. This has been shown for a variety of nonphotosynthetic eukaryotes, such as, for example, apicomplexan parasites (Fast et al. 2001; Roos et al. 2002; Williams and Keeling 2003; Huang et al. 2004), perkinsids (Stelter et al. 2007; Matsuzaki et al. 2008; Fernández Robledo et al. 2011) or nonphotosynthetic dinoflagellates (Sanchez-Puerta et al. 2007; Slamovits and Keeling 2008), and green algae (de Koning and Keeling 2004). Although much more controversial, potential EGTs have also been used to propose a photosynthetic ancestry for ciliates (Reyes-Prieto et al. 2008) or that algae with secondary plastids of red algal origin, such as diatoms and chromerids, may have contained green algal endosymbionts in their past (Moustafa et al. 2009; Woehle et al. 2011). Likewise, several dozens of potential EGTs have been detected in algae and plants that appear to have been acquired from Chlamydiae, a group of parasitic bacteria (Huang and Gogarten 2007; Becker et al. 2008; Moustafa et al. 2008), which led to proposing that cryptic chlamydial endosymbionts may have helped to establish the first plastids, in particular, by providing essential functions for plastid activity (Greub and Raoult 2003; Ball et al. 2013; Baum 2013).We revise here some of these cases of cryptic endosymbiosis, with special attention on the difficulties in accurately detecting EGT and the importance of proper phylogenetic analysis and of an adequate taxonomic sampling to achieve that task.