Mitochondrial iron metabolism in plants: frataxin comes into play

Friedreich ataxia (FRDA), an autosomal recessive neurological dysfunction that severely impairs motor coordination and reduction of life expectancy in humans, is caused by a deficiency in frataxin, a nuclear-encoded mitochondrial protein. Recently, a frataxin ortholog has been identified in Arabidopsis thaliana, named AtFH, with a transit peptide for localization in mitochondria and 65% sequence identity with human frataxin (Busi et al. FEBS Lett 576:141–144, 2004). Complementation of S. cerevisiae mutant strain Δyfh1 deficient in frataxin with AtFH, proved that the plant isoform is a functional protein, able to restore normal respiration and growth rates in the mutant yeast (Busi et al. FEBS Lett 576:141–144, 2004). AtFH is localized in mitochondria as its animal counterparts (Busi et al. Plant J 48:873–882, 2006); it is expressed mainly in flowers and developing embryos and it is an essential protein, since the knocking out of AtFH gene causes arrest of embryo development at the globular stage (Vazzola et al. FEBS Lett 581:667–672, 2007). A T-DNA insertional A.thaliana mutant showing a greater than 50% reduction of AtFH protein content, named atfh-1, has impaired activity of two mitochondrial enzymes possessing [Fe-S] clusters: aconitase and succinate dehydrogenase (Busi et al. Plant J 48:873–882, 2006). The results obtained in the last ten years on animal systems can contribute, without any doubt, to the elucidation of the role of frataxin in plant mitochondria; however, mitochondria of photosynthetically active cells, differently from animal ones, are not the major source of Reactive Oxygen Species (ROS) which could suggest possible differences in function between plant and animal frataxin.     

Plant biotechnology for food security and bioeconomy

This year is a special year for plant biotechnology. It was 30 years ago, on January 18 1983, one of the most important dates in the history of plant biotechnology, that three independent groups described Agrobacterium tumefaciens—mediated genetic transformation at the Miami Winter Symposium, leading to the production of normal, fertile transgenic plants (Bevan et al. in Nature 304:184–187, 1983; Fraley et al. in Proc Natl Acad Sci USA 80:4803–4807, 1983; Herrera-Estrella et al. in EMBO J 2:987–995, 1983; Vasil in Plant Cell Rep 27:1432–1440, 2008). Since then, plant biotechnology has rapidly advanced into a useful and valuable tool and has made a significant impact on crop production, development of a biotech industry and the bio-based economy worldwide.     

Optimized dendritic cell-based immunotherapy for melanoma: the TriMix-formula

Since decades, the main goal of tumor immunologists has been to increase the capacity of the immune system to mediate tumor regression. In this regard, one of the major focuses of cancer immunotherapy has been the design of vaccines promoting strong tumor-specific cytotoxic T lymphocyte responses in cancer patients. Here, dendritic cells (DCs) play a pivotal role as they are regarded as nature’s adjuvant and as such have become the natural agents for antigen delivery in order to finally elicit strong T cell responses (Villadangos and Schnorrer in Nat Rev Immunol 7:543–555, 2007; Melief in Immunity 29:372–383, 2008; Palucka and Banchereau in Nat Rev Cancer 12:265–277, 2012; Vacchelli et al. in Oncoimmunology 2:e25771, 2013; Galluzzi et al. in Oncoimmunology 1:1111–1134, 2012). Therefore, many investigators are actively pursuing the use of DCs as an efficient way of inducing anticancer immune responses. Nowadays, DCs can be generated at a large scale in closed systems, yielding sufficient numbers of cells for clinical application. In addition, with the identification of tumor-associated antigens, which are either selectively or preferentially expressed by tumors, a whole range of strategies using DCs for immunotherapy have been designed and tested in clinical studies. Despite the evidence that DCs loaded with tumor-associated antigens can elicit immune responses in vivo, clinical responses remained disappointingly low. Therefore, optimization of the cellular product and route of administration was urgently needed. Here, we review the path we have followed in the development of TriMixDC-MEL, a potent DC-based cellular therapy, discussing its development as well as further modifications and applications.     

Agarose plating and a bead type culture technique enable and stimulate development of protoplast-derived colonies in a number of plant species

Two novel techniques improve division and colony formation from protoplasts:

1. Plating in agarose stimulates colony formation of protoplasts from a wide range of species. Protoplasts from Nicotiana tabacum developed to colonies from lower initial population densities in agarose than in agar or liquid. Protoplasts from Hyoscyamus muticus which do not divide in agar divided and formed colonies in agarose at higher efficiencies than in liquid medium.
2. Culture of gel embedded protoplasts in large volumes of liquid medium on a gyrotatory shaker (‘bead culture’) further improved plating efficiencies in some species (e.g. Lycopersicon esculentum and Crepis capillaris) and enabled sustained proliferation of protoplasts which had not previously developed beyond the few cell colony stage (Brassica rapa and a mutator gene variety of Petunia hybrida).

The combination of ‘agarose plating’ and ‘bead culture’ dramatically improved plating efficiencies of protoplasts in all species tested.     

Transduction of pressure signal to electrical signal upon sudden increase in turgor pressure in Chara corallina

By taking advantage of large cell size of Chara corallina, we analyzed the membrane depolarization induced by decreased turgor pressure (Shimmen in J Plant Res 124:639–644, 2011). In the present study, the response to increased turgor pressure was analyzed. When internodes were incubated in media containing 200 mM dimethyl sulfoxide, their intracellular osmolality gradually increased and reached a steady level after about 3 h. Upon removal of dimethyl sulfoxide, turgor pressure quickly increased. In response to the increase in turgor pressure, the internodes generated a transient membrane depolarization at its nodal end. The refractory period was very long and it took about 2 h for full recovery after the depolarizing response. Involvement of protein synthesis in recovery from refractoriness was suggested, based on experiments using inhibitors.     

A radically non-morphemic approach to bidirectional syncretism

This paper addresses the question of how certain kinds of overlapping syncretisms in inflectional paradigms can be accounted for that Baerman et al. (Language 80:807–824, 2005) refer to as convergent/divergent bidirectional syncretisms (based on earlier work by Stump, Inflectional morphology, 2001). Bidirectional syncretism strongly resists accounts in terms of standard rules of exponence (or similar devices) that correlate inflection markers with (often underspecified) morpho-syntactic specifications (such rules are used in many morphological theories; e.g., Anderson, A-morphous morphology, 1992; Halle and Marantz in The view from building, pp. 111–176, 1993; Aronoff, Morphology by itself, 1994; Wunderlich in Yearbook of morphology 1995, pp. 93–114, 1996; and Stump, Inflectional morphology, 2001). The reason is that it is difficult to capture overlapping distributions by natural classes. In view of this, rules of referral have been proposed to derive bidirectional syncretism (Stump, Inflectional morphology, 2001; Baerman et al. (Language 80:807–824, 2005)). In contrast, I would like to pursue the hypothesis that systematic instances of overlapping syncretism ultimately motivate a new approach to inflectional morphology—one that fully dispenses with the assumption that morphological exponents are paired with morpho-syntactic feature specifications (and that therefore qualifies as radically non-morphemic): First, rules of exponence are replaced with feature co-occurrence restrictions (FCRs; Gazdar et al., Generalized Phrase Structure Grammar, 1985). For phonologically determined natural classes of exponents, FCRs state incompatibilites with morpho-syntactic feature specifications. Second, marker competition is resolved by a principle of Phonology-driven Marker Selection (PMS). PMS takes over the role of the Specificity (Blocking, Elsewhere, Panini) Principle of standard analyses. Empirically, the main focus is on Bonan declension; the analysis is subsequently extended to Gujarati conjugation and Latin o-declension, with further remarks on bidirectional syncretism in other inflectional paradigms.     

Isolation of Hyphomonas Strains that Induce Normal Morphogenesis in Protoplasts of the Marine Red Alga Pyropia yezoensis

Marine macroalgae cannot develop normal morphology under axenic conditions although normal morphogenesis can be sustained when certain bacteria are present. In this study, bacteria that induced normal morphogenesis in the red alga Pyropia yezoensis (Nori) were identified. The bacteria were isolated from algal media, thalli, tissue debris, and purified protoplasts during protoplast isolation from P. yezoensis laboratory cultures. 16S rRNA gene sequence analysis showed these bacterial isolates belonged to α-Proteobacteria (12 groups), γ-Proteobacteria (3 groups), and Flavobacteria (2 groups). Axenic protoplasts of P. yezoensis generated by removing epiphytic bacteria were co-cultured along with the bacterial isolates. Most axenic protoplasts showed irregular morphogenetic and anaplastic cells; cells with normal morphology were scarce. However, inoculation with 11 strains of Hyphomonas (α-Proteobacteria) led to significantly higher normal morphogenetic rates (4.5–7.3 %, P?Hyphomonas strains were recovered from all experiments; thus, certain Hyphomonas strains can induce normal morphogenesis in P. yezoensis protoplasts. Direct inoculation of the Hyphomonas strain exhibited higher morphogenetic activity than inoculation of its extracellular and intracellular products. This is the first study demonstrating the influence of specific bacteria on protoplast morphology in marine macroalgae.     

A model of direction selectivity in the starburst amacrine cell network

Displaced starburst amacrine cells (SACs) are retinal interneurons that exhibit GABA _A receptor-mediated and Cl ^? cotransporter-mediated, directionally selective (DS) light responses in the rabbit retina. They depolarize to stimuli that move centrifugally through the receptive field surround and hyperpolarize to stimuli that move centripetally through the surround (Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006). They also play a key role in the activity of DS ganglion cells (DS GC; Amthor et al, Vis Neurosci 19:495–509 2002; Euler et al, Nature 418:845–852, 2002; Fried et al, Nature 420:411– 414, 2002; Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006; Lee and Zhou, Neuron 51:787–799 2006; Yoshida et al, Neuron 30:771–780, 2001). In this paper we present a model of strong DS behavior of SACs which relies on the GABA-mediated communication within a tightly interconnected network of these cells and on the glutamate signal that the SACs receive from bipolar cells (a presynaptic cell that receives input from cones). We describe how a moving light stimulus can produce a large, sustained depolarization of the SAC dendritic tips that point in the direction that the stimulus moves (i.e., centrifugal motion), but produce a minimal depolarization of the dendritic tips that point in the opposite direction (i.e., centripetal motion). This DS behavior, which is quantified based on the relative size and duration of the depolarizations evoked by stimulus motion at dendritic tips pointing in opposite directions, is robust to changes of many different parameter values and consistent with experimental data. In addition, the DS behavior is strengthened under the assumptions that the Cl^? cotransporters Na^?+?-K^?+?-Cl^?? and K^?+?-Cl^?? are located in different regions of the SAC dendritic tree (Gavrikov et al, PNAS 103(49):18793–18798, 2006) and that GABA evokes a long-lasting response (Gavrikov et al, PNAS 100(26):16047–16052, 2003, PNAS 103(49):18793–18798, 2006; Lee and Zhou, Neuron 51:787–799, 2006). A possible mechanism is discussed based on the generation of waves of local glutamate and GABA secretion, and their postsynaptic interplay as the waves travel between cell compartments.     

Manufacturing of peptides exhibiting biological activity

Numerous studies have shown that food proteins may be a source of bioactive peptides. Those peptides are encrypted in the protein sequence. They stay inactive within the parental protein until release by proteolytic enzymes (Mine and Kovacs-Nolan in Worlds Poult Sci J 62(1):87–95, 2006; Hartman and Miesel in Curr Opin Biotechnol 18:163–169, 2007). Once released the bioactive peptides exhibit several biofunctionalities and may serve therapeutic roles in body systems. Opioid peptides, peptides lowering high blood pressure, inhibiting platelet aggregation as well as being carriers of metal ions and peptides with immunostimulatory, antimicrobial and antioxidant activities have been described (Hartman and Miesel in Curr Opin Biotechnol 18:163–169, 2007). The biofunctional abilities of the peptides have therefore aroused a lot of scientific, technological and consumer interest with respect to the role of dietary proteins in controlling and influencing health (Möller et al. in Eur J Nutr 47(4):171–182, 2008). Biopeptides may find wide application in food production, the cosmetics industry as well as in the prevention and treatment of various medical conditions. They are manufactured by chemical and biotechnological methods (Marx in Chem Eng News 83(11):17–24. 2005; Hancock and Sahl in Nat Biotechnol 24(12):1551–1557, 2006). Depending on specific needs (food or pharmaceutical industry) different degrees of peptide purifications are required. This paper discusses the practicability of manufacturing bioactive peptides, especially from food proteins.     

Modeling the role of altruism of antibiotic-resistant bacteria

Based on the new findings in a recent experimental study (Lee et al., Nature 467, 82–86, 2010) that antibiotic resistant mutants of bacteria produce indoles to protect the wild strain bacteria, we propose a mathematical model to describe the evolution of the wild strain, resistant strain and indoles with limited nutrient. We distinguish two cases: (i) mutation is negligible and a resistant strain preexists; (ii) mutation is not negligible. For (i), we establish conditions for co-persistence of both strains, which indicate that the wild strain can survive with the help from the altruistic resistant strain, whereas it dies out in the absence of such a benefit. This consolidates the experimental findings in Lee et al. (Nature 467:82–86 2010). Further analysis and simulations also reveal some new phenomena not reported in Lee et al. (Nature 467:82–86 2010), that is, periodic oscillations of the populations may occur within certain range of the parameters, and there exists bistability in the sense that a stable positive periodic solution coexists with a stable positive equilibrium.     

An analysis of a ‘community-driven’ reconstruction of the human metabolic network

Following a strategy similar to that used in baker’s yeast (Herrgård et al. Nat Biotechnol 26:1155–1160, 2008). A consensus yeast metabolic network obtained from a community approach to systems biology (Herrgård et al. 2008; Dobson et al. BMC Syst Biol 4:145, 2010). Further developments towards a genome-scale metabolic model of yeast (Dobson et al. 2010; Heavner et al. BMC Syst Biol 6:55, 2012). Yeast 5—an expanded reconstruction of the Saccharomyces cerevisiae metabolic network (Heavner et al. 2012) and in Salmonella typhimurium (Thiele et al. BMC Syst Biol 5:8, 2011). A community effort towards a knowledge-base and mathematical model of the human pathogen Salmonella typhimurium LT2 (Thiele et al. 2011), a recent paper (Thiele et al. Nat Biotechnol 31:419–425, 2013). A community-driven global reconstruction of human metabolism (Thiele et al. 2013) described a much improved ‘community consensus’ reconstruction of the human metabolic network, called Recon 2, and the authors (that include the present ones) have made it freely available via a database at http://humanmetabolism.org/ and in SBML format at Biomodels (http://identifiers.org/biomodels.db/MODEL1109130000). This short analysis summarises the main findings, and suggests some approaches that will be able to exploit the availability of this model to advantage.     

A module is a module is a module: evolution of modularity in Evolutionary Psychology

The concept of modularity has been central in behavioral and neural sciences since the publication of Fodor’s The Modularity of Mind (1983). Fodor strived to explain the functional architecture of the mind based on the distinction between modular and central systems. Modular systems were deemed to have certain architectural features, such as automaticity, encapsulation, and domain specificity. Evolutionary psychologists have adopted the concept to characterize purportedly evolved human adaptations. In an influential paper, Barrett and Kurzban (Psychol Rev 113(3):628–647, 2006) proposed a definition of modules purely in terms of functional specialization. It is here argued that such strategy marks a shift in Evolutionary Psychology’s theoretical emphasis, as it trivializes the investigation of proximate causes in evolutionary theorizing; furthermore, it leaves the door open to too much flexibility on what counts as evidence for purportedly evolved modules.     

A dynamical systems perspective on the relationship between symbolic and non-symbolic computation

It has been claimed that connectionist (artificial neural network) models of language processing, which do not appear to employ “rules”, are doing something different in kind from classical symbol processing models, which treat “rules” as atoms (e.g., McClelland and Patterson in Trends Cogn Sci 6(11):465–472, 2002). This claim is hard to assess in the absence of careful, formal comparisons between the two approaches. This paper formally investigates the symbol-processing properties of simple dynamical systems called affine dynamical automata, which are close relatives of several recurrent connectionist models of language processing (e.g., Elman in Cogn Sci 14:179–211, 1990). In line with related work (Moore in Theor Comput Sci 201:99–136, 1998; Siegelmann in Neural networks and analog computation: beyond the Turing limit. Birkhäuser, Boston, 1999), the analysis shows that affine dynamical automata exhibit a range of symbol processing behaviors, some of which can be mirrored by various Turing machine devices, and others of which cannot be. On the assumption that the Turing machine framework is a good way to formalize the “computation” part of our understanding of classical symbol processing, this finding supports the view that there is a fundamental “incompatibility” between connectionist and classical models (see Fodor and Pylyshyn 1988; Smolensky in Behav Brain Sci 11(1):1–74, 1988; beim Graben in Mind Matter 2(2):29--51,2004b). Given the empirical successes of connectionist models, the more general, super-Turing framework is a preferable vantage point from which to consider cognitive phenomena. This vantage may give us insight into ill-formed as well as well-formed language behavior and shed light on important structural properties of learning processes.     

Neither touch nor vision: sensory substitution as artificial synaesthesia?

Block (Trends Cogn Sci 7:285–286, 2003) and Prinz (PSYCHE 12:1–19, 2006) have defended the idea that SSD perception remains in the substituting modality (auditory or tactile). Hurley and Noë (Biol Philos 18:131–168, 2003) instead argued that after substantial training with the device, the perceptual experience that the SSD user enjoys undergoes a change, switching from tactile/auditory to visual. This debate has unfolded in something like a stalemate where, I will argue, it has become difficult to determine whether the perception acquired through the coupling with an SSD remains in the substituting or the substituted modality. Within this puzzling deadlock two new approaches have been recently suggested. Ward and Meijer (Conscious Cogn 19:492–500, 2010) describe SSD perception as visual-like but characterize it as a kind of artificially induced synaesthesia. Auvray et al. (Perception 36:416–430, 2007) and Auvray and Myin (Cogn Sci 33:1036–1058, 2009) suggest that SSDs let their users experience a new kind of perception. Deroy and Auvray (forthcoming) refine this position, and argue that this new kind of perception depends on pre-existing senses without entirely aligning with any of them. So, they have talked about perceptual experience in SSDs as going "beyond vision". In a similar vein, MacPherson (Oxford University Press, New York, 2011a) claims that “if the subjects (SSD users) have experiences with both vision-like and touch-like representational characteristics then perhaps they have a sense that ordinary humans do not” (MacPherson in Oxford University Press, New York, 2011a, p. 139).     

The Macamide N-3-Methoxybenzyl-Linoleamide Is a Time-Dependent Fatty Acid Amide Hydrolase (FAAH) Inhibitor

The Peruvian plant Lepidium meyenii (Maca) has been shown to possess neuroprotective activity both in vitro and in vivo [1–3]. Previous studies have also demonstrated the activity of the pentane extract and its macamides, the most representative lipophilic constituents of Maca, in the endocannabinoid system as fatty acid amide hydrolase (FAAH) inhibitors. One of the most active macamides, N-3-methoxybenzyl-linoleamide [4, 5], was studied to determine its mechanism of interaction with FAAH and whether it has inhibitory activity on mono-acyl glycerol lipase (MAGL), the second enzyme responsible for endocannabinoid degradation [6]. Macamide concentrations from 1 to 100 μM were tested using FAAH and MAGL inhibitor assay methods and showed no effect on MAGL. Tests with other conditions were performed in order to characterize the inhibitory mechanism of FAAH inhibition. N-3-methoxybenzyl-linoleamide displayed significant time-dependent and dose-dependent FAAH inhibitory activity. The mechanism of inhibition was most likely irreversible or slowly reversible. These results suggest the potential application of macamides isolated from Maca as FAAH inhibitors, as they might act on the central nervous system to provide analgesic, anti-inflammatory, or neuroprotective effects, by modulating the release of neurotransmitters.     

Taxonomic review of Kyphosus (Pisces: Kyphosidae) in the Atlantic and Eastern Pacific Oceans

The taxonomy of the Atlantic and Eastern Pacific species of Kyphosus is reviewed with K. bosquii (Lacepède 1802), K. incisor (Cuvier 1831), K. analogus (Gill 1862) and K. elegans (Peters 1869) considered valid, and K. atlanticus sp. nov. newly described. Kyphosus bosquii and K. atlanticus are both characterized by 12 dorsal- and 11 anal-fin soft rays, but differ in the number of longitudinal scale rows along the midbody (61–66, mode 63 vs. 50–56, mode 54). Kyphosus incisor and K. analogus, characterized by 14 dorsal- and 13 anal-fin soft rays, similarly differ from each other in midbody longitudinal scale row counts (57–64, mode 60 vs. 68–74, mode 70 or 72). Kyphosus elegans is characterized by 13 dorsal- and 12 anal-fin soft rays, and 51–57 midbody longitudinal scale rows. Kyphosus bosquii, K. atlanticus and K. incisor are distributed in the Atlantic Ocean, K. analogus and K. elegans occurring in the Eastern Pacific. The holotype of Pimelepterus flavolineatus Poey 1866, here regarded as a junior synonym of K. incisor, was located within a collection of Cuban fishes donated to the Smithsonian Institution by Poey in 1873. A neotype is designated here for K. analogus. Pimelepterus gallveii Cunningham 1910, Kyphosus palpebrosus Miranda-Ribeiro 1919 and K. metzelaari Jordan and Evermann 1927 are recognized as junior synonyms of K. bosquii. Pimelepterus sandwicensis Sauvage 1880 is a junior synonym of K. elegans. Perca saltatrix Linnaeus 1758, together with the replacement name Perca sectatrix Linnaeus 1766, is regarded as nomina dubia.     

Flow cytometric analysis of tobacco and cowpea protoplasts infected in vivo and in vitro with alfalfa mosaic virus

Immunofluorescence flow cytometry was used to study the distribution of viral antigen in protoplast populations. Protoplasts were isolated from healthy and alfalfa mosaic virus (AMV) infected tobacco leaves (designated in vivo infected). Furthermore isolated tobacco and cowpea protoplasts were infected in vitro with AMV. The FITC-conjugated antibodies could penetrate formaldehyde fixed protoplasts. The flow cytometric measurements were rapid and reproducible. Comparable immunofluorescence patterns were found for all infected samples (per sample 10⁴ protoplasts were measured). Infectious virus could only be detected in in vivo infected tobacco protoplasts and in in vitro infected cowpea protoplasts.