Negative Feedback Enables Fast and Flexible Collective Decision-Making in Ants

Positive feedback plays a major role in the emergence of many collective animal behaviours. In many ants pheromone trails recruit and direct nestmate foragers to food sources. The strong positive feedback caused by trail pheromones allows fast collective responses but can compromise flexibility. Previous laboratory experiments have shown that when the environment changes, colonies are often unable to reallocate their foragers to a more rewarding food source. Here we show both experimentally, using colonies of Lasius niger, and with an agent-based simulation model, that negative feedback caused by crowding at feeding sites allows ant colonies to maintain foraging flexibility even with strong recruitment to food sources. In a constant environment, negative feedback prevents the frequently found bias towards one feeder (symmetry breaking) and leads to equal distribution of foragers. In a changing environment, negative feedback allows a colony to quickly reallocate the majority of its foragers to a superior food patch that becomes available when foraging at an inferior patch is already well underway. The model confirms these experimental findings and shows that the ability of colonies to switch to a superior food source does not require the decay of trail pheromones. Our results help to resolve inconsistencies between collective foraging patterns seen in laboratory studies and observations in the wild, and show that the simultaneous action of negative and positive feedback is important for efficient foraging in mass-recruiting insect colonies.     

Specific processing of tenascin-C by the metalloprotease meprinβ neutralizes its inhibition of cell spreading

The metalloprotease meprin has been implicated in tissue remodelling due to its capability to degrade extracellular matrix components. Here, we investigated the susceptibility of tenascin-C to cleavage by meprinβ and the functional properties of its proteolytic fragments. A set of monoclonal antibodies against chicken and human tenascin-C allowed the mapping of proteolytic fragments generated by meprinβ. In chicken tenascin-C, meprinβ processed all three major splicing variants by removal of 10 kDa N-terminal and 38 kDa C-terminal peptides, leaving a large central part of subunits intact. A similar cleavage pattern was found for large human tenascin-C variant where two N-terminal peptides (10 or 15 kDa) and two C-terminal fragments (40 and 55 kDa) were removed from the intact subunit. N-terminal sequencing revealed the exact amino acid positions of cleavage sites. In both chicken and human tenascin-C N-terminal cleavages occurred just before and/or after the heptad repeats involved in subunit oligomerization. In the human protein, an additional cleavage site was identified in the alternative fibronectin type III repeat D. Whereas all these sites are known to be attacked by several other proteases, a unique cleavage by meprinβ was located to the 7th constant fibronectin type III repeat in both chicken and human tenascin-C, thereby removing the C-terminal domain involved in its anti-adhesive activity. In cell adhesion assays meprinβ-digested human tenascin-C was not able to interfere with fibronectin-mediated cell spreading, confirming cleavage in the anti-adhesive domain. Whereas the expression of meprinβ and tenascin-C does not overlap in normal colon tissue, inflamed lesions of the mucosa from patients with Crohn's disease exhibited many meprinβ-positive leukocytes in regions where tenascin-C was strongly induced. Our data indicate that, at least under pathological conditions, meprinβ might attack specific functional sites in tenascin-C that are important for its oligomerization and anti-adhesive activity.     

Allicin and derivates are cysteine protease inhibitors with antiparasitic activity

Allicin and derivatives thereof inhibit the CAC1 cysteine proteases falcipain 2, rhodesain, cathepsin B and L in the low micromolar range. The structure–activity relationship revealed that only derivatives with primary carbon atom in vicinity to the thiosulfinate sulfur atom attacked by the active-site Cys residue are active against the target enzymes. Some compounds also show potent antiparasitic activity against Plasmodium falciparum and Trypanosoma brucei brucei.     

Non-Mendelian transmission of alleles at microsatellite loci: an example in Ixodes ricinus, the vector of Lyme disease

Microsatellite loci are usually considered to be neutral co-dominant and Mendelian markers. We undertook to study the inheritance of five microsatellite loci in the European Lyme disease vector, the tick Ixodes ricinus. Only two loci appeared fully Mendelian while the three others displayed non-Mendelian patterns that highly frequent null alleles could not fully explain. At one locus, IR27, some phenomenon seems to hinder the PCR amplification of one allele, depending on its origin (maternal imprinting) and/or its size (short allele dominance). DNA methylation, which appeared to be a possible explanation of this amplification bias, was rejected by a specific test comparing the amplification efficiency that did not differ between unmethylated and experimentally methylated DNA. The role of allele size in heterozygous individuals was then revealed from the data available on field collected ticks and consistent with the results of a theoretical approach. These observations highlight the need for prudence while inferring reproductive systems (selfing rates), parentage or even allelic frequencies from microsatellite markers, in particular for parasitic organisms for which molecular approaches often represent the only way for population biology inferences.     

Induced Variations in Brassinosteroid Genes Define Barley Height and Sturdiness,and Expand the Green Revolution Genetic Toolkit

Reduced plant height and culm robustness are quantitative characteristics important for assuring cereal crop yield and quality under adverse weather conditions. A very limited number of short-culm mutant alleles were introduced into commercial crop cultivars during the Green Revolution. We identified phenotypic traits, including sturdy culm, specific for deficiencies in brassinosteroid biosynthesis and signaling in semidwarf mutants of barley (Hordeum vulgare). This set of characteristic traits was explored to perform a phenotypic screen of near-isogenic short-culm mutant lines from the brachytic, breviaristatum, dense spike, erectoides, semibrachytic, semidwarf, and slender dwarf mutant groups. In silico mapping of brassinosteroid-related genes in the barley genome in combination with sequencing of barley mutant lines assigned more than 20 historic mutants to three brassinosteroid-biosynthesis genes (BRASSINOSTEROID-6-OXIDASE, CONSTITUTIVE PHOTOMORPHOGENIC DWARF, and DIMINUTO) and one brassinosteroid-signaling gene (BRASSINOSTEROID-INSENSITIVE1 [HvBRI1]). Analyses of F2 and M2 populations, allelic crosses, and modeling of nonsynonymous amino acid exchanges in protein crystal structures gave a further understanding of the control of barley plant architecture and sturdiness by brassinosteroid-related genes. Alternatives to the widely used but highly temperature-sensitive uzu1.a allele of HvBRI1 represent potential genetic building blocks for breeding strategies with sturdy and climate-tolerant barley cultivars.The introduction of dwarfing genes to increase culm sturdiness of cereal crops was crucial for the first Green Revolution (Hedden, 2003). The culms of tall cereal crops were not strong enough to support the heavy spikes of high-yielding cultivars, especially under high-nitrogen conditions. As a result, plants fell over, a process known as lodging. This caused losses in yield and grain-quality issues attributable to fungal infections, mycotoxin contamination, and preharvest germination (Rajkumara, 2008). Today, a second Green Revolution is on its way, to revolutionize the agricultural sector and to ensure food production for a growing world population. Concurrently, global climate change is expected to cause more frequent occurrences of extreme weather conditions, including thunderstorms with torrential rain and strong winds, thus promoting cereal culm breakage (Porter and Semenov, 2005; National Climate Assessment Development Advisory Committee, 2013). Accordingly, plant architectures that resist lodging remain a major crop-improvement goal and identification of genes that regulate culm length is required to enhance the genetic toolbox in order to facilitate efficient marker-assisted breeding. The mutations and the corresponding genes that enabled the Green Revolution in wheat (Triticum aestivum) and rice (Oryza sativa) have been identified (Hedden, 2003). They all relate to gibberellin metabolism and signal transduction. It is now known that other plant hormones such as brassinosteroids are also involved in the regulation of plant height. Knowledge of the molecular mechanisms underlying the effects of the two hormones on cell elongation and division has mainly come from studies in Arabidopsis (Arabidopsis thaliana; Bai et al., 2012). Mutant-based breeding strategies to fine-tune brassinosteroid metabolism and signaling pathways could improve lodging behavior in modern crops (Vriet et al., 2012) such as barley (Hordeum vulgare), which is the fourth most abundant cereal in both area and tonnage harvested (http://faostat.fao.org).A short-culm phenotype in crops is often accompanied by other phenotypic changes. Depending on the penetrance of such pleiotropic characters, but also the parental background and different scientific traditions and expertise, short-culmed barley mutants were historically divided into groups, such as brachytic (brh), breviaristatum (ari), dense spike (dsp), erectoides (ert), semibrachytic (uzu), semidwarf (sdw), or slender dwarf (sld; Franckowiak and Lundqvist, 2012). Subsequent mutant characterization was limited to intragroup screens and very few allelism tests between mutants from different groups have been reported (Franckowiak and Lundqvist, 2012). Although the total number of short-culm barley mutants exceeds 500 (Franckowiak and Lundqvist, 2012), very few have been characterized at the DNA level (Helliwell et al., 2001; Jia et al., 2009; Chandler and Harding, 2013; Houston et al., 2013). One of the first identified haplotypes was uzu barley (Chono et al., 2003). The Uzu1 gene encodes the brassinosteroid hormone receptor and is orthologous to the BRASSINOSTEROID-INSENSITIVE1 (BRI1) gene of Arabidopsis, a crucial promoter of plant growth (Li and Chory, 1997). The uzu1.a allele has been used in East Asia for over a century and is presently distributed in winter barley cultivars in Japan, the Korean peninsula, and China (Saisho et al., 2004). Its agronomic importance comes from the short and sturdy culm that provides lodging resistance, and an upright plant architecture that tolerates dense planting.Today, more than 50 different brassinosteroids have been identified in plants (Bajguz and Tretyn, 2003). Most are intermediates of the complex biosynthetic pathway (Shimada et al., 2001). Approximately nine genes code for the enzymes that participate in the biosynthetic pathway from episterol to brassinolide (Supplemental Fig. S1). Brassinosteroid deficiency is caused by down-regulation of these genes, but it can also be associated with brassinosteroid signaling. The first protein in the signaling network is the brassinosteroid receptor encoded by BRI1 (Li and Chory, 1997; Kim and Wang, 2010). In this work, we show how to visually identify brassinosteroid-mutant barley plants and we describe more than 20 relevant mutations in four genes of the brassinosteroid biosynthesis and signaling pathways that can be used in marker-assisted breeding strategies.     

MetaboLights: towards a new COSMOS of metabolomics data management

Exciting funding initiatives are emerging in Europe and the US for metabolomics data production, storage, dissemination and analysis. This is based on a rich ecosystem of resources around the world, which has been build during the past ten years, including but not limited to resources such as MassBank in Japan and the Human Metabolome Database in Canada. Now, the European Bioinformatics Institute has launched MetaboLights, a database for metabolomics experiments and the associated metadata (http://www.ebi.ac.uk/metabolights). It is the first comprehensive, cross-species, cross-platform metabolomics database maintained by one of the major open access data providers in molecular biology. In October, the European COSMOS consortium will start its work on Metabolomics data standardization, publication and dissemination workflows. The NIH in the US is establishing 6?C8 metabolomics services cores as well as a national metabolomics repository. This communication reports about MetaboLights as a new resource for Metabolomics research, summarises the related developments and outlines how they may consolidate the knowledge management in this third large omics field next to proteomics and genomics.     

Multilevel Societies in New World Primates? Flexibility May Characterize the Organization of Peruvian Red Uakaris (Cacajao calvus ucayalii)

Researchers have described multilevel societies with one-male, multifemale units (OMUs) forming within a larger group in several catarrhine species, but not in platyrhines. OMUs in multilevel societies are associated with extremely large group sizes, often with >100 individuals, and the only platyrhine genus that forms groups of this size is Cacajao. We review available evidence for multilevel organization and the formation of OMUs in groups of Cacajao, and test predictions for the frequency distribution patterns of male–male and male–female interindividual distances within groups of red-faced uakaris (Cacajao calvus ucayalii), comparing year-round data with those collected at the peak of the breeding season, when group cohesion may be more pronounced. Groups of Cacajao fission and fuse, forming subgroup sizes at frequencies consistent with an OMU organization. In Cacajao calvus ucayalii and Cacajao calvus calvus, bachelor groups are also observed, a characteristic of several catarrhine species that form OMUs. However, researchers have observed both multimale–multifemale groups and groups with a single male and multiple females in Cacajao calvus. The frequency distributions of interindividual distances for male–male and male–female dyads are consistent with an OMU-based organization, but alternative interpretations of these data are possible. The distribution of interindividual distances collected during the peak breeding season differed from those collected year-round, indicating seasonal changes in the spatial organization of Cacajao calvus ucayalii. We suggest a high degree of flexibility may characterize the social organization of Cacajao calvus ucayalii, which may form OMUs under certain conditions. Further studies with identifiable individuals, thus far not possible in Cacajao, are required to confirm the social organization.     

A high risk phenotype of hypertrophic cardiomyopathy associated with a compound genotype of two mutated β-myosin heavy chain genes

Hypertrophic cardiomyopathy (HCM) is a genetically and clinically heterogeneous myocardial disease that is in most cases familial and transmitted in a dominant fashion. The most frequently affected gene codes for the cardiac (ventricular) β-myosin heavy chain. We have investigated the genetic cause of an isolated case of HCM, which was marked by an extremely severe phenotype and a very early age of onset. HCM is normally not a disease of small children. The proband was a boy who had suffered cardiac arrest at the age of 6.5years (resuscitation by cardioconversion). Upon screening of the β-myosin heavy chain gene as a candidate, two missense mutations, one in exon19 (Arg719Trp) and a second in exon12 (Met349Thr), were identified. The Arg719Trp mutation was de novo, as it was not found in the parents. In contrast, the Met349Thr mutation was inherited through the maternal grandmother. Six family members were carriers of this mutation but only the proband was clinically affected. Segregation and molecular analysis allowed us to assign the Met349Thr mutation to the maternal and the Arg719Trp de novo mutation to the paternal β-myosin allele. Thus, the patient has no normal myosin. We interpret these findings in terms of compound heterozygosity of a dominant (Arg719Trp) and a recessive (Met349Thr) mutation. Whereas a single mutated Arg719Trp allele would be sufficient to cause HCM, the concurrent Met349Thr mutation alone does not apparently induce the disease. Nevertheless, it conceivably contributes to the particularly severe phenotype. Received: 15 September 1997 / Accepted: 26 November 1997