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.     

Neural Crest and Olfactory System: New Prospective

Sensory neurons in vertebrates are derived from two embryonic transient cell sources: neural crest (NC) and ectodermal placodes. The placodes are thickenings of ectodermal tissue that are responsible for the formation of cranial ganglia as well as complex sensory organs that include the lens, inner ear, and olfactory epithelium. The NC cells have been indicated to arise at the edges of the neural plate/dorsal neural tube, from both the neural plate and the epidermis in response to reciprocal interactions Moury and Jacobson (Dev Biol 141:243?C253, 1990). NC cells migrate throughout the organism and give rise to a multitude of cell types that include melanocytes, cartilage and connective tissue of the head, components of the cranial nerves, the dorsal root ganglia, and Schwann cells. The embryonic definition of these two transient populations and their relative contribution to the formation of sensory organs has been investigated and debated for several decades (Basch and Bronner-Fraser, Adv Exp Med Biol 589:24?C31, 2006; Basch et al., Nature 441:218?C222, 2006) review (Baker and Bronner-Fraser, Dev Biol 232:1?C61, 2001). Historically, all placodes have been described as exclusively derived from non-neural ectodermal progenitors. Recent genetic fate-mapping studies suggested a NC contribution to the olfactory placodes (OP) as well as the otic (auditory) placodes in rodents (Murdoch and Roskams, J Neurosci Off J Soc Neurosci 28:4271?C4282, 2008; Murdoch et al., J Neurosci 30:9523?C9532, 2010; Forni et al., J Neurosci Off J Soc Neurosci 31:6915?C6927, 2011b; Freyer et al., Development 138:5403?C5414, 2011; Katoh et al., Mol Brain 4:34, 2011). This review analyzes and discusses some recent developmental studies on the OP, placodal derivatives, and olfactory system.     

Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene

MYH9 has been proposed as a major genetic risk locus for a spectrum of nondiabetic end stage kidney disease (ESKD). We use recently released sequences from the 1000 Genomes Project to identify two western African-specific missense mutations (S342G and I384M) in the neighboring APOL1 gene, and demonstrate that these are more strongly associated with ESKD than previously reported MYH9 variants. The APOL1 gene product, apolipoprotein L-1, has been studied for its roles in trypanosomal lysis, autophagic cell death, lipid metabolism, as well as vascular and other biological activities. We also show that the distribution of these newly identified APOL1 risk variants in African populations is consistent with the pattern of African ancestry ESKD risk previously attributed to MYH9. Mapping by admixture linkage disequilibrium (MALD) localized an interval on chromosome 22, in a region that includes the MYH9 gene, which was shown to contain African ancestry risk variants associated with certain forms of ESKD (Kao et al. 2008; Kopp et al. 2008). MYH9 encodes nonmuscle myosin heavy chain IIa, a major cytoskeletal nanomotor protein expressed in many cell types, including podocyte cells of the renal glomerulus. Moreover, 39 different coding region mutations in MYH9 have been identified in patients with a group of rare syndromes, collectively termed the Giant Platelet Syndromes, with clear autosomal dominant inheritance, and various clinical manifestations, sometimes also including glomerular pathology and chronic kidney disease (Kopp 2010; Sekine et al. 2010). Accordingly, MYH9 was further explored in these studies as the leading candidate gene responsible for the MALD signal. Dense mapping of MYH9 identified individual single nucleotide polymorphisms (SNPs) and sets of such SNPs grouped as haplotypes that were found to be highly associated with a large and important group of ESKD risk phenotypes, which as a consequence were designated as MYH9-associated nephropathies (Bostrom and Freedman 2010). These included HIV-associated nephropathy (HIVAN), primary nonmonogenic forms of focal segmental glomerulosclerosis, and hypertension affiliated chronic kidney disease not attributed to other etiologies (Bostrom and Freedman 2010). The MYH9 SNP and haplotype associations observed with these forms of ESKD yielded the largest odds ratios (OR) reported to date for the association of common variants with common disease risk (Winkler et al. 2010). Two specific MYH9 variants (rs5750250 of S-haplotype and rs11912763 of F-haplotype) were designated as most strongly predictive on the basis of Receiver Operating Characteristic analysis (Nelson et al. 2010). These MYH9 association studies were then also extended to earlier stage and related kidney disease phenotypes and to population groups with varying degrees of recent African ancestry admixture (Behar et al. 2010; Freedman et al. 2009a, b; Nelson et al. 2010), and led to the expectation of finding a functional African ancestry causative variant within MYH9. However, despite intensive efforts including re-sequencing of the MYH9 gene no suggested functional mutation has been identified (Nelson et al. 2010; Winkler et al. 2010). This led us to re-examine the interval surrounding MYH9 and to the detection of novel missense mutations with predicted functional effects in the neighboring APOL1 gene, which are significantly more associated with ESKD than all previously reported SNPs in MYH9.     

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.     

Mitochondrial complex I inhibitors, acetogenins, induce HepG2 cell death through the induction of the complete apoptotic mitochondrial pathway

The development of new anti-neoplastic drugs is a key issue for cancer chemotherapy due to the reality that, most likely, certain cancer cells are resistant to current chemotherapy. The past two decades have witnessed tremendous advances in our understanding of the pathogenesis of cancer. These advances have allowed identification new targets as oncogenes, tumor supressor genes and the possible implication of the mitochondria (Fulda et al. Nat Rev Drug Discov 9:447–464, 2010). Annonaceous Acetogenins (ACGs) have been described as the most potent inhibitors of the respiratory chain because of their interaction with mitochondrial Complex I (Degli Esposti and Ghelli Biochim Biophys Acta 1187:116–120, 1994; Zafra-Polo et al. Phytochemistry 42:253–271, 1996; Miyoshi et al. Biochim Biophys Acta 1365:443–452, 1998; Tormo et al. Arch Biochem Biophys 369:119–126, 1999; Motoyama et al. Bioorg Med Chem Lett 12:2089–2092, 2002). To explore a possible application of natural products from Annonaceous plants to cancer treatment, we have selected four bis-tetrahydrofuranic ACGs, three from Annona cherimolia (cherimolin-1, motrilin and laherradurin) and one from Rollinia mucosa (rollinianstatin-1) in order to fully describe their mechanisms responsible within the cell (Fig. 1). In this study, using a hepato-carcinoma cell line (HepG2) as a model, we showed that the bis-THF ACGs caused cell death through the induction of the apoptotic mitochondrial pathway. Their potency and behavior were compared with the classical mitochondrial respiratory chain Complex I inhibitor rotenone in every apoptotic pathway step.

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.     

1H, 13C,and 15N backbone and side chain resonance assignments of thermophilic Geobacillus kaustophilus cyclophilin-A

Cyclophilins catalyze the reversible peptidyl-prolyl isomerization of their substrates and are present across all kingdoms of life from humans to bacteria. Although numerous biological roles have now been discovered for cyclophilins, their function was initially ascribed to their chaperone-like activity in protein folding where they catalyze the often rate-limiting step of proline isomerization. This chaperone-like activity may be especially important under extreme conditions where cyclophilins are often over expressed, such as in tumors for human cyclophilins (Lee Archiv Pharm Res 33(2): 181–187, 2010), but also in organisms that thrive under extreme conditions, such as theromophilic bacteria. Moreover, the reversible nature of the peptidyl-prolyl isomerization reaction catalyzed by cyclophilins has allowed these enzymes to serve as model systems for probing the role of conformational changes during catalytic turnover (Eisenmesser et al. Science 295(5559): 1520–1523, 2002; Eisenmesser et al. Nature 438(7064): 117–121, 2005). Thus, we present here the resonance assignments of a thermophilic cyclophilin from Geobacillus kaustophilus derived from deep-sea sediment (Takami et al. Extremophiles 8(5): 351–356, 2004). This thermophilic cyclophilin may now be studied at a variety of temperatures to provide insight into the comparative structure, dynamics, and catalytic mechanism of cyclophilins.     

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.     

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.     

ORIUM: Optimized RDC-based Iterative and Unified Model-free analysis

Residual dipolar couplings (RDCs) are NMR parameters that provide both structural and dynamic information concerning inter-nuclear vectors, such as N–H^N and Cα–Hα bonds within the protein backbone. Two approaches for extracting this information from RDCs are the model free analysis (MFA) (Meiler et al. in J Am Chem Soc 123:6098–6107, 2001; Peti et al. in J Am Chem Soc 124:5822–5833, 2002) and the direct interpretation of dipolar couplings (DIDCs) (Tolman in J Am Chem Soc 124:12020–12030, 2002). Both methods have been incorporated into iterative schemes, namely the self-consistent RDC based MFA (SCRM) (Lakomek et al. in J Biomol NMR 41:139–155, 2008) and iterative DIDC (Yao et al. in J Phys Chem B 112:6045–6056, 2008), with the goal of removing the influence of structural noise in the MFA and DIDC formulations. Here, we report a new iterative procedure entitled Optimized RDC-based Iterative and Unified Model-free analysis (ORIUM). ORIUM unifies theoretical concepts developed in the MFA, SCRM, and DIDC methods to construct a computationally less demanding approach to determine these structural and dynamic parameters. In all schemes, dynamic averaging reduces the actual magnitude of the alignment tensors complicating the determination of the absolute values for the generalized order parameters. To readdress this scaling issue that has been previously investigated (Lakomek et al. in J Biomol NMR 41:139–155, 2008; Salmon et al. in Angew Chem Int Edit 48:4154–4157, 2009), a new method is presented using only RDC data to establish a lower bound on protein motion, bypassing the requirement of Lipari–Szabo order parameters. ORIUM and the new scaling procedure are applied to the proteins ubiquitin and the third immunoglobulin domain of protein G (GB3). Our results indicate good agreement with the SCRM and iterative DIDC approaches and signify the general applicability of ORIUM and the proposed scaling for the extraction of inter-nuclear vector structural and dynamic content.     

Isolation of monomeric photosystem II that retains the subunit PsbS

Photosystem II has been purified from a transplastomic strain of Nicotiana tabacum according to two different protocols. Using the procedure described in Piano et al. (Photosynth Res 106:221–226, 2010) it was possible to isolate highly active PSII composed of monomers and dimers but depleted in their PsbS protein content. A “milder” procedure than the protocol reported by Fey et al. (Biochim Biophys Acta 1777:1501–1509, 2008) led to almost exclusively monomeric PSII complexes which in part still bind the PsbS protein. This finding might support a role for PSII monomers in higher plants.     

Proposal to replace the illegitimate genus name Prescottia Jones et al. 2013 with the genus name Prescottella gen. nov. and to replace the illegitimate combination Prescottia equi Jones et al. 2013 with Prescottella equi comb. nov

Recently we proposed that Rhodococcus equi (Magnusson 1923) Goodfellow and Alderson 1977 be transferred to a novel genus, Prescottia, as Prescottia equi comb. nov. However, in accordance with Principle 2 and Rule 51b(4) of the Bacteriological Code (1990 Revision), the bacterial genus name Prescottia Jones et al. 2013 is deemed illegitimate as this name has been used previously for a plant genus within the family Orchidaceae. Consequently, a new genus name, Prescottella gen. nov. is proposed for the bacterial taxon and a new combination Prescottella equi comb. nov. is proposed for the type species.     

Integrating participatory approaches into social life cycle assessment: the SLCA participatory approach

Purpose

This article discusses the choice of stakeholder categories and the integration of stakeholders into participatory processes to define impact categories and select indicators.

Methods

We undertook a literature review concerning the roles and the importance of stakeholders in participatory processes, and the use of such processes in environmental and social LCAs (Biswas et al. Int J Life Cycle Assess 3(4):184-190, 1998; Sonnemann et al. Int J Life Cycle Assess 6(6):325-333, 2001; Baldo Int J Life Cycle Assess 7(5):269-275, 2002; James et al. Int J Life Cycle Assess 7(3):151-157, 2002; Bras-Kapwijk Int J Life Cycle Assess 8(5):266-272, 2003; Mettier et al. Int J Life Cycle Assess 11(6):468-476, 2006). As part of the French National Research Agency Piscenlit project, we adapted the Principle, Criteria, Indicator (PCI) method (Rey-Valette et al. 2008), which is an assessment method of sustainable development, as a way to integrate the participatory approach into Social Life Cycle Assessment (SLCA) methodology, mainly at the impact definition stage.

Results and discussion

Different views of participation were found in the literature; there is no consensual normative approach for the implication of stakeholders in LCA development. Some attempts have been made to integrate stakeholders into environmental LCAs but these attempts have not been generalized. However, they strongly emphasize the interrelationship between research on the growing integration of stakeholders and on the choice of stakeholders. We then propose criteria from stakeholder theory (Freeman 1984; Mitchell et al. Acad Manage Rev 22(4):853-886, 1997; Geibler et al. Bus Strat Environ 15:334-346, 2006) in order to identify relevant stakeholders for SLCA participatory approach. The adaptation of the PCI method to Principles, Impacts, and Indicators (PII) enables stakeholders to express themselves and hence leads to definitions of relevant social indicators that they can appropriate. The paper presents results regarding the selection of stakeholders but no specific results regarding the choice of impact categories and indicators.

Conclusions and recommendations

Integrating a participatory approach into SLCAs is of interest at several levels. It enables various factors to be taken into account: plurality of stakeholder interests, local knowledge, and impact categories that make sense for stakeholders in different contexts. It also promotes dialogue and simplifies the search for indicators. However, it requires a multidisciplinary approach and the integration of new knowledge and skills for the SLCA practitioners.     

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.     

Constructions and headedness in derivation and compounding

The ??traditional?? distinction of compounds into endocentric (Eng. doorknob) and exocentric (pickpocket) is based on the presence or absence of a head constituent (Bloomfield, Language, Holt, New York, 1933); since the early eighties, the syntactic notion of ??head?? has been extended also to derivation, claiming that English derivational suffixes, as e.g. -ness, are heads, either in an absolute sense or in a categorial sense (see Williams Linguist Inq 12:245?C274, 1981; Lieber On the organization of the lexicon, Indiana university Linguistics Club, Bloomington, 1981; Lieber, in Yearbook of morphology 1989, Foris, Dordrecht, 1989; among others). In this paper, we shall first review some key issues in the morphological notion of head, illustrating well-known problematic cases, and then we shall discuss the Construction Morphology approach to headedness in derivation and compounding (Booij in The Oxford handbook of compounding, Oxford University Press, Oxford, 2009; Booij, in Cross-disciplinary issues in compounding, John Benjamins, Amsterdam, 2010a, 2010 Booij, Construction morphology, Oxford University Press, Oxford, 2010b). The stipulation of a hierarchical lexicon with subschemas expressing intermediate generalizations is a powerful theoretical device in accounting for a phenomenon as headedness variation, as we shall show with a Vietnamese case study; also, inconsistencies in word-class assignment in derivation will be dealt with in a constructionist perspective. Moreover, we shall discuss the consequences of a constructionist approach to the distinction between compounding and derivation.     

EZ-ASSIGN, a program for exhaustive NMR chemical shift assignments of large proteins from complete or incomplete triple-resonance data

For several of the proteins in the BioMagResBank larger than 200 residues, 60 % or fewer of the backbone resonances were assigned. But how reliable are those assignments? In contrast to complete assignments, where it is possible to check whether every triple-resonance Generalized Spin System (GSS) is assigned once and only once, with incomplete data one should compare all possible assignments and pick the best one. But that is not feasible: For example, for 200 residues and an incomplete set of 100 GSS, there are 1.6 × 10²⁶⁰ possible assignments. In “EZ-ASSIGN”, the protein sequence is divided in smaller unique fragments. Combined with intelligent search approaches, an exhaustive comparison of all possible assignments is now feasible using a laptop computer. The program was tested with experimental data of a 388-residue domain of the Hsp70 chaperone protein DnaK and for a 351-residue domain of a type III secretion ATPase. EZ-ASSIGN reproduced the hand assignments. It did slightly better than the computer program PINE (Bahrami et al. in PLoS Comput Biol 5(3):e1000307, 2009) and significantly outperformed SAGA (Crippen et al. in J Biomol NMR 46:281–298, 2010), AUTOASSIGN (Zimmerman et al. in J Mol Biol 269:592–610, 1997), and IBIS (Hyberts and Wagner in J Biomol NMR 26:335–344, 2003). Next, EZ-ASSIGN was used to investigate how well NMR data of decreasing completeness can be assigned. We found that the program could confidently assign fragments in very incomplete data. Here, EZ-ASSIGN dramatically outperformed all the other assignment programs tested.     

Remodelling of collagen fibre transition stretch and angular distribution in soft biological tissues and cell-seeded hydrogels

The extracellular matrix in many biological tissues is adapted to its mechanical environment. In this study, a phenomenological model for collagen remodelling is introduced that incorporates angular remodelling (fibre reorientation) and the adaptation of the so-called transition stretch. This is achieved by introducing a local stress-free configuration for the collagen network by a multiplicative decomposition of the deformation gradient and the appropriate definition of the anisotropic free Helmholtz energy potentials and structure tensors. The collagen network is either treated using discrete fibre directions or a continuous angular distribution. The first part of the study illustrates the influence of force- and displacement-controlled loading on either stress- or deformation-driven remodelling processes in tissues with various degrees of fibre reinforcement. The model is then applied to recent experimental studies of collagen remodelling, specifically periosteum adaptation (Foolen et?al. in J Biomech 43(16):3168–3176, 2010), collagen gel (Thomopoulos et?al. in J Biomech Eng 127(5):742–750, 2005) and fibrin cruciform (Sander et?al. in Ann Biomed Eng 1–16, 2010) compaction. The model is able to capture the basic effects of an adapting transition stretch over time in the periosteal simulations, as well as the compaction and the development of structural anisotropy in the collagen and fibrin gels. The model can potentially be applied to elucidate structure–function relationships, better interpret in vitro experiments involving collagen remodelling, and help investigate aspects of certain pathologies, such as connective tissue contracture.     

Reply to: “Comment on root orientation can affect detection accuracy of ground-penetrating radar”

Introduction

We showed that root orientation affected a parameter of ground penetrating radar (GPR), amplitude area (A) (Tanikawa et al. Plant Soil 373:317–327, 2013). The aims of this reply to Wu et al. (2014) are (i) to correct the two inaccuracies in Tanikawa et al. (2013) and (ii) to improve our method of estimating A(90°) using A(x) of root angle x.

Methods

Measured A values of Tanikawa et al. (2013) were analyzed with the modified equations.

Results

The first inaccuracy was the use of incorrect units for the coefficient b (the phase shift) in the sinusoidal waveform of A(x). The units should have been radians instead of degrees. The second inaccuracy was the mis-derivation of A(x) into A(x?+?90°). In the modified method, A(90°) was estimated by A(x) from two orthogonally intersecting transect lines and a transect line at a diagonal to them.

Conclusions

The two inaccuracies did not affect the previous main conclusions that the parameter T was suitable for estimating root diameter and that grid transects are likely to identify clear hyperbolas reflecting roots in radar profiles (Tanikawa et al. 2013). By the improved method, we could accurately estimate root diameter by scanning using three transect lines intersecting at angles of x, x?+?45°, and x?+?90°.     

The (Paleo)Geography of Evolution: Making Sense of Changing Biology and Changing Continents

During the voyage of the H.M.S. Beagle, Charles Darwin quickly realized that geographic isolation led to significant changes in the adaptation of local flora and fauna (Darwin 1859). Genetic isolation is one of the well-known mechanisms by which adaptation (allopatric speciation) can occur (Palumbi, Annu Rev Ecol Syst 25:547?C72, 1994; Ricklefs, J Avian Biol 33:207?C11, 2002; Burns et al., Evolution 56:1240?C52, 2002; Hendry et al., Science 290:516?C8, 2009). Evolutionary changes can also occur when landmasses converge or are ??bridged.?? An important and relatively recent (Pliocene Epoch) example known as the ??Great American Biotic Interchange?? allowed for the migration of previously isolated species into new ecological niches between North and South America (Webb 1985, Ann Mo Bot Gard 93:245?C57, 2006; Kirby and MacFadden, Palaeogeogr Palaeoclimatol Palaeoecol 228:193?C202, 2005). Geographic isolation (vicariance) or geographic merging (geodispersal) can occur for a variety of reasons (sea level rise, splitting of continents, mountain building). In addition, the growth of a large supercontinent (or breakup) may change the climatic zonation on the globe and form a different type of barrier for species migration. This short review paper focuses on changing paleogeography throughout the Phanerozoic and the close ties between paleogeography and the evolutionary history of life on Earth.     

A Mathematical and Numerical Investigation of the Hemodynamical Origins of Oscillations in Microvascular Networks

Evidence is presented to show that self-sustained oscillations of purely hemodynamical origin are possible in some arcade-type microvascular networks supplied with steady boundary conditions, but that in others the oscillations disappear with sufficient reduction of the time step Δt, showing them to be numerical artefacts. In an attempt to elucidate the mechanisms involved in the onset of fluctuations, we proceed to perform a linear stability analysis for the convective model of Kiani et al. (Microvasc. Res. 45:219–232, 1993; Am. J. Physiol. 266(35):H1822–H1828, 1994), and show that this leads via a system of delay differential equations to a nonlinear eigenvalue problem. This result generalises the characteristic equation obtained by Carr et al. (Ann. Biomed. Eng. 33:764–771, 2005) and Geddes et al. (SIAM J. Appl. Dyn. Syst. 6(4):694–727, 2007) who solved a special case in a two node network. An implicit numerical method is proposed for the computation of blood flows in networks using the convective model. In a moderate size subnetwork of one of the networks chosen by Kiani et al. (Am. J. Physiol. 266(35):H1822–H1828, 1994), the topology, vessel lengths, and diameters of which were based on microvascular networks in the rat mesentery, we compare results generated using the original explicit numerical method of Kiani et al. (Am. J. Physiol. 266(35):H1822–H1828, 1994) with those from our implicit scheme. From the linear stability theory, a critical value D _RBC,crit of a red blood cell diameter parameter D _RBC in the plasma skimming model of Fenton et al. (Pflügers Arch. 403:396–401, 1985b) is identified for the onset of oscillations about steady state and both the explicit and implicit methods are used to calculate the inflow hematocrit solutions in all vessels of the subnetwork at the critical parameter value, subject to perturbed initial conditions. The results of the implicit method are demonstrated to be in excellent and superior agreement with the predictions of the linear analysis in this case. For values of D _RBC slightly larger than D _RBC,crit the bifurcating periodic solutions calculated using either the explicit or implicit schemes are characteristic of those of a supercritical Hopf bifurcation and the graphs of D _RBC vs. oscillation amplitude would seem to converge as Δt→0.