Inedible producers in food webs: controls on stoichiometric food quality and composition of grazers

Ecological stoichiometry and food web theories focus on distinct mechanisms that shape communities. These mechanisms, however, likely interact in ways that neither theory alone addresses. To illustrate, we show how a model that tracks flow of energy and nutrients through two producers and two grazers reveals two indirect, interrelated roles for "neutrally inedible" producers. First, inedible producers can exert controls over the nutrient content of edible producers and indirectly influence whether grazers are nutrient or energy limited. Second, through these controls, inedible producers can shape community assembly by excluding grazers that are weak competitors for nutrients contained in edible producers. A mesocosm experiment revealed patterns consistent with both predictions: high abundances of inedible algae were accompanied by low phosphorus contents of edible algae and low abundances of the grazer Daphnia. Both lines of inference suggest that interactions between stoichiometry and plant heterogeneity may shape plankton communities.     

A novel family of membrane-bound E3 ubiquitin ligases

A novel E3 ubiquitin ligase family that consists of viral E3 ubiquitin ligases (E3s) and their mammalian homologues was recently discovered. These novel E3s are membrane-bound molecules that share the secondary structure and catalytic domain for E3 activity. All family members have two transmembrane regions at the center and a RING-CH domain at the amino terminus. Forced expression of these novel E3s has been shown to reduce the surface expression of various membrane proteins through ubiquitination of target molecules. Initial examples of viral E3s were identified in Kaposi's sarcoma associated herpesvirus (KSHV) and murine gamma-herpesvirus 68 (MHV-68) and have been designated as modulator of immune recognition (MIR) 1, 2 and mK3, respectively. MIR 1, 2 and mK3 are able to down-regulate MHC class I molecule expression, and mK3 is required to establish an effective latent viral infection in vivo. The first characterized mammalian homologue to MIR 1, 2 and mK3 is c-MIR/MARCH VIII. Forced expression of c-MIR/MARCH VIII down-regulates B7-2, a co-stimulatory molecule important for antigen presentation. Subsequently, several mammalian molecules related to c-MIR/MARCH VIII have been characterized and named as membrane associated RING-CH (MARCH) family. However, the precise physiological function of MARCH family members remains as yet unknown.     

Antimicrobial constituents of Scrophularia deserti

A study of the chemistry and antibacterial activity of Scrophularia deserti led to the isolation of eight compounds, including the metabolite 3(zeta)-hydroxy-octadeca-4(E),6(Z)-dienoic acid (1). The known compounds ajugoside (2), scropolioside B (3), 6-O-alpha-L-rhamnopyranosylcatalpol (4), buddlejoside A(8) (5), scrospioside A (6), laterioside (7) and 3R-1-octan-3-yl-3-O-beta-D-glucopyranoside (8) were also isolated. Compounds 1-3 exhibited moderate antibacterial activity against strains of multidrug and methicillin-resistant Staphylococcus aureus (MRSA) and a panel of rapidly growing mycobacteria with minimum inhibitory concentration (MIC) values ranging from 32 to 128 microg/ml.     

Diversity arrays technology (DArT) for high-throughput profiling of the hexaploid wheat genome

Despite a substantial investment in the development of panels of single nucleotide polymorphism (SNP) markers, the simple sequence repeat (SSR) technology with a limited multiplexing capability remains a standard, even for applications requiring whole-genome information. Diversity arrays technology (DArT) types hundreds to thousands of genomic loci in parallel, as previously demonstrated in a number diploid plant species. Here we show that DArT performs similarly well for the hexaploid genome of bread wheat (Triticum aestivum L.). The methodology previously used to generate DArT fingerprints of barley also generated a large number of high-quality markers in wheat (99.8% allele-calling concordance and approximately 95% call rate). The genetic relationships among bread wheat cultivars revealed by DArT coincided with knowledge generated with other methods, and even closely related cultivars could be distinguished. To verify the Mendelian behaviour of DArT markers, we typed a set of 90 Cranbrook × Halberd doubled haploid lines for which a framework (FW) map comprising a total of 339 SSR, restriction fragment length polymorphism (RFLP) and amplified fragment length polymorphism (AFLP) markers was available. We added an equal number of DArT markers to this data set and also incorporated 71 sequence tagged microsatellite (STM) markers. A comparison of logarithm of the odds (LOD) scores, call rates and the degree of genome coverage indicated that the quality and information content of the DArT data set was comparable to that of the combined SSR/RFLP/AFLP data set of the FW map.Electronic Supplementary Material Supplementary material is available in the online version of this article at and is accessible for authorized users.     

4,5,6‐Trisubstituted Piperidinones as Conformationally Restricted Ceramide Analogues: Synthesis and Evaluation as Inhibitors of Sphingosine and Ceramide Kinases and as NKT Cell‐Stimulatory Antigens

The conformationally based piperidinone sphingosine analogues 7, 8, 15 , and 16 were synthesized from allylic alcohol 34 via lactams 31 and 32 . The l‐ arabino diol 7 and the l‐ ribo diol 8 were transformed into the amino alcohols 17 – 24 . The l‐ gluco ceramide analogues 43, 46a , and 47 , and the l‐ altro ceramide analogues 51a and 52 were synthesized from either 31 or 32 . The l‐ ribo diols 8 and 16 , and the amino alcohols 19 and 20 inhibit sphingosine kinase 1 (SPHK1), while the l‐ arabino analogues 7, 15, 17 , and 18 are inactive. The l‐ arabino and the l‐ ribo dimethylamines 21 – 24 , the l‐ gluco ceramide analogues 43, 46a , and 47 , and the l‐ altro ceramide analogues 51a and 52 did not block SPHK1. Neither the l‐ arabino diol 7 nor the l‐ ribo diol 8 inhibited SPHK2 or ceramide kinase. The l‐ arabino diols 7 and 15 stimulate invariant natural killer T (iNKT) cells when presented by living antigen‐presenting cells (APC) and also by plate‐bound human CD1d, whereas the l‐ ribo diols 8 and 16 , the l‐ arabino amino alcohols 17 – 18 , and the dimethylamines 21 – 22 did not activate iNKT cells. The l‐ gluco ceramide analogues 43, 46a , and 47 had strongly stimulatory effects on iNKT cells when presented by living APC and also by plate‐bound human CD1d, whereas the l‐ altro ceramide analogue 52 activated only weakly. All activatory compounds induced preferentially the release of pro‐inflammatory cytokines, indicating the formation of a stable CD1d? lipid? T‐cell receptor complex.     

Structural and functional studies of trans-encoded HLA-DQ2.3 (DQA1*03:01/DQB1*02:01) protein molecule

MHC class II molecules are composed of one α-chain and one β-chain whose membrane distal interface forms the peptide binding groove. Most of the existing knowledge on MHC class II molecules comes from the cis-encoded variants where the α- and β-chain are encoded on the same chromosome. However, trans-encoded class II MHC molecules, where the α- and β-chain are encoded on opposite chromosomes, can also be expressed. We have studied the trans-encoded class II HLA molecule DQ2.3 (DQA1*03:01/DQB1*02:01) that has received particular attention as it may explain the increased risk of certain individuals to type 1 diabetes. We report the x-ray crystal structure of this HLA molecule complexed with a gluten epitope at 3.05 Å resolution. The gluten epitope, which is the only known HLA-DQ2.3-restricted epitope, is preferentially recognized in the context of the DQ2.3 molecule by T-cell clones of a DQ8/DQ2.5 heterozygous celiac disease patient. This preferential recognition can be explained by improved HLA binding as the epitope combines the peptide-binding motif of DQ2.5 (negative charge at P4) and DQ8 (negative charge at P1). The analysis of the structure of DQ2.3 together with all other available DQ crystal structures and sequences led us to categorize DQA1 and DQB1 genes into two groups where any α-chain and β-chain belonging to the same group are expected to form a stable heterodimer.     

Clock Genes Influence Gene Expression in Growth Plate and Endochondral Ossification in Mice

We have previously shown transient promotion by parathyroid hormone of Period-1 (Per1) expression in cultured chondrocytes. Here we show the modulation by clock genes of chondrogenic differentiation through gene transactivation of the master regulator of chondrogenesis Indian hedgehog (IHH) in chondrocytes of the growth plate. Several clock genes were expressed with oscillatory rhythmicity in cultured chondrocytes and rib growth plate in mice, whereas chondrogenesis was markedly inhibited in stable transfectants of Per1 in chondrocytic ATDC5 cells and in rib growth plate chondrocytes from mice deficient of brain and muscle aryl hydrocarbon receptor nuclear translocator-like (BMAL1). Ihh promoter activity was regulated by different clock gene products, with clear circadian rhythmicity in expression profiles of Ihh in the growth plate. In BMAL1-null mice, a predominant decrease was seen in Ihh expression in the growth plate with a smaller body size than in wild-type mice. BMAL1 deficit led to disruption of the rhythmic expression profiles of both Per1 and Ihh in the growth plate. A clear rhythmicity was seen with Ihh expression in ATDC5 cells exposed to dexamethasone. In young mice defective of BMAL1 exclusively in chondrocytes, similar abnormalities were found in bone growth and Ihh expression. These results suggest that endochondral ossification is under the regulation of particular clock gene products expressed in chondrocytes during postnatal skeletogenesis through a mechanism relevant to the rhythmic Ihh expression.     

Adipocytokine Orosomucoid Integrates Inflammatory and Metabolic Signals to Preserve Energy Homeostasis by Resolving Immoderate Inflammation

Orosomucoid (ORM), also called α-1 acid glycoprotein, is an abundant plasma protein that is an immunomodulator induced by stressful conditions such as infections. In this study, we reveal that Orm is induced selectively in the adipose tissue of obese mice to suppress excess inflammation that otherwise disturbs energy homeostasis. Adipose Orm levels were elevated by metabolic signals, including insulin, high glucose, and free fatty acid, as well as by the proinflammatory cytokine tumor necrosis factor-α, which is found in increased levels in the adipose tissue of morbid obese subjects. In both adipocytes and macrophages, ORM suppressed proinflammatory gene expression and pathways such as NF-κB and mitogen-activated protein kinase signalings and reactive oxygen species generation. Concomitantly, ORM relieved hyperglycemia-induced insulin resistance as well as tumor necrosis factor-α-mediated lipolysis in adipocytes. Accordingly, ORM improved glucose and insulin tolerance in obese and diabetic db/db mice. Taken together, our results suggest that ORM integrates inflammatory and metabolic signals to modulate immune responses to protect adipose tissue from excessive inflammation and thereby from metabolic dysfunction.