Conflicts of interest and the evolution of decision sharing

Social animals regularly face consensus decisions whereby they choose, collectively, between mutually exclusive actions. Such decisions often involve conflicts of interest between group members with respect to preferred action. Conflicts could, in principle, be resolved, either by sharing decisions between members (‘shared decisions’) or by one ‘dominant’ member making decisions on behalf of the whole group (‘unshared decisions’). Both, shared and unshared decisions, have been observed. However, it is unclear as to what favours the evolution of either decision type. Here, after a brief literature review, we present a novel method, involving a combination of self-organizing system and game theory modelling, of investigating the evolution of shared and unshared decisions. We apply the method to decisions on movement direction. We find that both, shared and unshared, decisions can evolve without individuals having a global overview of the group''s behaviour or any knowledge about other members'' preferences or intentions. Selection favours unshared over shared decisions when conflicts are high relative to grouping benefits, and vice versa. These results differ from those of group decision models relating to activity timings. We attribute this to fundamental differences between collective decisions about modalities that are disjunct (here, space) or continuous (here, time) with respect to costs/benefits.     

A glucuronyltransferase involved in glucuronoxylan synthesis in pea (Pisum sativum) epicotyls.

A particulate enzyme preparation made from epicotyls of 1-week-old etiolated pea (Pisum sativum) seedlings was shown to incorporate glucuronic acid from UDP-D-[U-14C]glucuronic acid into a hemicellulosic polysaccharide. Optimum conditions for the incorporation include the presence of Mn2+ ions at between 4 and 10 mmol/litre and a pH between 5 and 6. UDP-D-xylose at 1 mmol/litre allows incorporation to continue for at least 8 h. In its absence, the reaction stops within 30 min. Analysis of the product by partial and total acid hydrolysis, followed by paper chromatography or electrophoresis, indicates that the polysaccharide produced is a glucuronoxylan.     

Drug-delivering nerve conduit improves regeneration in a critical-sized gap

Autologous nerve grafts are the current “gold standard” for repairing large nerve gaps. However, they cause morbidity at the donor nerve site and only a limited amount of nerve can be harvested. Nerve conduits are a promising alternative to autografts and can act as guidance cues for the regenerating axons, without the need to harvest donor nerve. Separately, it has been shown that localized delivery of GDNF can enhance axon growth and motor recovery. FK506, an FDA approved small molecule, has also been shown to enhance peripheral nerve regeneration. This paper describes the design of a novel hole-based drug delivery apparatus integrated with a polytetrafluoroethylene (PTFE) nerve conduit for controlled local delivery of a protein such as GDNF or a small molecule such as FK506. The PTFE devices were tested in a diffusion chamber, and the bioactivity of the released media was evaluated by measuring neurite growth of dorsal root ganglions (DRGs) exposed to the released drugs. The drug delivering nerve guide was able to release bioactive concentrations of FK506 or GDNF. Following these tests, optimized drug releasing nerve conduits were implanted across 10 mm sciatic nerve gaps in a BL6 yellow fluorescent protein (YFP) mouse model, where they demonstrated significant improvement in muscle mass, compound muscle action potential, and axon myelination in vivo as compared with nerve conduits without the drug. The drug delivery nerve guide could release drug for extended periods of time and enhance axon growth in vitro and in vivo.     

The oligodeoxynucleotide sequences corresponding to never-expressed peptide motifs are mainly located in the non-coding strand

Background  

We study the usage of specific peptide platforms in protein composition. Using the pentapeptide as a unit of length, we find that in the universal proteome many pentapeptides are heavily repeated (even thousands of times), whereas some are quite rare, and a small number do not appear at all. To understand the physico-chemical-biological basis underlying peptide usage at the proteomic level, in this study we analyse the energetic costs for the synthesis of rare and never-expressed versus frequent pentapeptides. In addition, we explore residue bulkiness, hydrophobicity, and codon number as factors able to modulate specific peptide frequencies. Then, the possible influence of amino acid composition is investigated in zero- and high-frequency pentapeptide sets by analysing the frequencies of the corresponding inverse-sequence pentapeptides. As a final step, we analyse the pentadecamer oligodeoxynucleotide sequences corresponding to the never-expressed pentapeptides.     

HISTORICAL BIOGEOGRAPHY IN NORTH AMERICAN ARID REGIONS: AN APPROACH USING MITOCHONDRIAL-DNA PHYLOGENY IN GRASSHOPPER MICE (GENUS ONYCHOMYS)

Restriction-endonuclease-site variation of mitochondrial DNA (mtDNA) was used to investigate patterns of geographic and phylogenetic divergence within the rodent genus Onychomys. Onychomys has occupied arid habitats in the western North American deserts, shrub-steppes, and grasslands since the late Tertiary. A phylogenetic analysis of the total mtDNA restriction-site variation throughout the range of Onychomys suggests that the distribution of this genus has been affected by the same Quaternary pluvial-interpluvial climatic fluctuations that have resulted in the periodic fragmentation of arid habitats in western North America. Onychomys mtDNA haplotypes define at least five discrete geographical subsets, suggesting that there are five areas of endemism for biota restricted to arid and semiarid habitats in North America. The mtDNA-haplotype phylogeny can be used to infer an hypothesis of historical relationships among the five areas of endemism as follows: ([{(Wyoming Basin + Interior Plains + Colorado Plateaus) + (Columbia Basin + Great Basin)} + Gulf Coastal Plain] + Chihuahuan) + Western Deserts. The results of this study point to the potential use of mtDNA-haplotype phylogenies to reconstruct historical biogeographic events in Quaternary time. The utility of mtDNA variation depends in part on the ecology and distribution of the species being examined. Therefore, our hypothesized area cladogram can be tested by investigating regional relationships in other western North American taxa with distributions similar to Onychomys.     

Neurally-derived nitric oxide regulates vascular tone in pulmonary and cutaneous arteries of the toad, Bufo marinus

In this study, the role of nitric oxide (NO) in regulation of the pulmocutaneous vasculature of the toad, Bufo marinus was investigated. In vitro myography demonstrated the presence of a neural NO signaling mechanism in both arteries. Vasodilation induced by nicotine was inhibited by the soluble guanylyl cyclase (GC) inhibitor, 1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one, and the NO synthase (NOS) inhibitor, N(omega)-nitro-l-arginine (l-NNA). Removal of the endothelium had no significant effect on the vasodilation. Furthermore, pretreatment with N(5)-(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO), a more specific inhibitor of neural NOS, caused a significant decrease in the nicotine-induced dilation. In the pulmonary artery only, a combination of l-NNA and the calcitonin gene-related peptide (CGRP) receptor antagonist, CGRP((8-37)), completely blocked the nicotine-induced dilation. In both arteries, the vasodilation was also significantly decreased by glibenclamide, an ATP-sensitive K(+) (K(+)(ATP)) channel inhibitor. Levcromakalim, a K(+)(ATP) channel opener, caused a dilation that was blocked by glibenclamide in both arteries. In the pulmonary artery, NO donor-mediated dilation was significantly decreased by pretreatment with glibenclamide. The physiological data were supported by NADPH-diaphorase histochemistry and immunohistochemistry, which demonstrated NOS in perivascular nerve fibers but not the endothelium of the arteries. These results indicate that the pulmonary and cutaneous arteries of B. marinus are regulated by NO from nitrergic nerves rather than NO released from the endothelium. The nitrergic vasodilation in the arteries appears to be caused, in part, via activation of K(+)(ATP) channels. Thus, NO could play an important role in determining pulmocutaneous blood flow and the magnitude of cardiac shunting.     

Expression, purification and characterisation of soluble GlfT and the identification of a novel galactofuranosyltransferase Rv3782 involved in priming GlfT-mediated galactan polymerisation in Mycobacterium tuberculosis

The arabinogalactan (AG) component of the mycobacterial cell wall is an essential branched polysaccharide which tethers mycolic acids (m) to peptidoglycan (P), forming the mAGP complex. Much interest has been focused on the biosynthetic machinery involved in the production of this highly impermeable shield, which is the target for numerous anti-tuberculosis agents. The galactan domain of AG is synthesised via a bifunctional galactofuranosyltransferase (GlfT), which utilises UDP-Galf as its high-energy substrate. However, it has proven difficult to study the protein in its recombinant form due to difficulties in recovering pure soluble protein using standard expression systems. Herein, we describe the effects of glfT co-induction with a range of chaperone proteins, which resulted in an appreciable yield of soluble protein at 5 mg/L after a one-step purification procedure. We have shown that this purified enzyme transfers [¹⁴C]Galf to a range of both β(1 → 5) and β(1 → 6) linked digalactofuranosyl neoglycolipid acceptors with a distinct preference for the latter. Ligand binding studies using intrinsic tryptophan fluorescence have provided supporting evidence for the apparent preference of this enzyme to bind the β(1 → 6) disaccharide acceptor. However, we could not detect binding or galactofuranosyltransferase activity with an n-octyl β-d-Gal-(1 → 4)-α-l-Rha acceptor, which mimics the reducing terminus of galactan in the mycobacterial cell wall. Conversely, after an extensive bioinformatics analysis of the H37Rv genome, further cloning, expression and functional analysis of the Rv3792 open reading frame indicates that this protein affords galactofuranosyltransferase activity against such an acceptor and paves the way for a better understanding of galactan biosynthesis in Mycobacterium tuberculosis.     

Loss of Core 1-derived O-Glycans Decreases Breast Cancer Development in Mice

Mucin-type core 1-derived O-glycans, one of the major types of O-glycans, are highly expressed in mammary gland epithelium. Abnormal O-glycans such as Tn antigen are found in over 90% of breast cancers; however, the in vivo role of these aberrant O-glycans in the etiology of breast cancer is unclear. We generated mice with mammary epithelial specific deletion of core 1-derived O-glycans. By crossing with two spontaneous mouse breast cancer models, we determined that loss of core 1-derived O-glycans delays the onset and progression of breast cancer development. Deficiency of core 1 O-glycosylation impaired the localization of Muc1, a major O-glycoprotein, on the apical surfaces of mammary epithelium. Signaling mediated by Muc1, which is critical for breast cancer development, was also defective in the absence of core 1 O-glycans. This study reveals an unexpected role of core 1-derived O-glycans in breast cancer development in mice.     

Modulation of chloride secretory responses and barrier function of intestinal epithelial cells by the Salmonella effector protein SigD

The Salmonella effector protein SigD is an inositol phosphate phosphatase that inhibits phosphatidylinositol 3-kinase-dependent signaling. Because epidermal growth factor (EGF) inhibits chloride secretion via phosphatidylinositol 3-kinase, we explored whether Salmonella infection might modify the inhibitory effect of EGF. As expected, EGF inhibited chloride secretion induced by carbachol in T₈₄ epithelial cells. Infection with wild-type (WT) but not sigD^– mutant S. typhimurium SL1344 decreased CCh-stimulated chloride secretion. Moreover, WT but not sigD^– Salmonella reduced the inhibitory effect of EGF on carbachol-stimulated chloride secretion. Complementation of sigD restored the ability of mutant Salmonella to reverse the inhibitory effect of EGF. EGF-induced EGF receptor phosphorylation was similar in cells infected with either WT or mutant Salmonella, and neither WT nor sigD^– Salmonella altered recruitment of the p85 subunit of phosphatidylinositol 3-kinase to EGF receptor, implying that SigD acts downstream of these signaling events. Furthermore, transepithelial resistance fell more rapidly in cells infected with WT vs. sigD^– Salmonella, indicating an early role for SigD in reducing barrier function, perhaps via activation of protein kinase C. We conclude that the Salmonella bacterial effector protein SigD may play critical roles in the pathogenesis of disease caused by this microorganism. chloride secretion; Salmonella typhimurium; epidermal growth factor