Human metabolic phenotypes link directly to specific dietary preferences in healthy individuals

Individual human health is determined by a complex interplay between genes, environment, diet, lifestyle, and symbiotic gut microbial activity. Here, we demonstrate a new "nutrimetabonomic" approach in which spectroscopically generated metabolic phenotypes are correlated with behavioral/psychological dietary preference, namely, "chocolate desiring" or "chocolate indifferent". Urinary and plasma metabolic phenotypes are characterized by differential metabolic biomarkers, measured using 1H NMR spectroscopy, including the postprandial lipoprotein profile and gut microbial co-metabolism. These data suggest that specific dietary preferences can influence basal metabolic state and gut microbiome activity that in turn may have long-term health consequences to the host. Nutrimetabonomics appears as a promising approach for the classification of dietary responses in populations and personalized nutritional management.     

Genetic consequences of Pleistocene fragmentation: Isolation, drift, and loss of diversity in rock iguanas (Cyclura)

Pleistocene fragmentation of the Great BahamaBank resulted in one large and several smallpopulations of rock iguanas (Cycluracychlura). We explore patterns of geneticvariation within and among these islandpopulations using mitochondrial sequence data(partial ND4 to tRNA^Leu) in combinationwith eight polymorphic microsatellite loci (2to 10 alleles). Genetic data support twophylogeographically distinct groups, AndrosIsland and the Exuma cays. This resultconflicts with current subspecific taxonomy inwhich three subspecies are described. Analysesof allelic data indicate that most islandpopulations are currently demographicallyindependent. Pairwise Fst values between eightisland populations range from 0.18 to 0.63, and6 of 135 individuals are misassigned in anassignment test. Population-genetic diversityis characterized using standard measures suchas number of alleles and heterozygosity (H) inaddition to a normalized Shannon-Weaver indexof diversity (D). We find genetic diversity inthe Andros Island population comparable to thatin other non-piscine animals (avg. # ofalleles = 5, avg. H = 0.56, avg. D = 0.66) while inthe Exuma cays populations these measures aremuch lower (avg. # of alleles = 2.75–1.625, avg.H = 0.43–0.17, avg. D = 0.45–0.18). These dataare used to discuss conservation managementstrategies, including prioritization andtranslocation.     

Bi-directional modulation of fast inhibitory synaptic transmission by leptin

The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABA_A receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABA_A receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABA_A receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability.     

Comparative genetics of invasive populations of walnut aphid,Chromaphis juglandicola,and its introduced parasitoid,Trioxys pallidus,in California

Coevolution may be an important component of the sustainability of importation biological control, but how frequently introduced natural enemies coevolve with their target pests is unclear. Here we explore whether comparative population genetics of the invasive walnut aphid, Chromaphis juglandicola, and its introduced parasitoid, Trioxys pallidus, provide insights into the localized breakdown of biological control services in walnut orchards in California. We found that sampled populations of C. juglandicola exhibited higher estimates of genetic differentiation (F_ST) than co‐occurring populations of T. pallidus. In contrast, estimates of both the inbreeding coefficient (G_IS) and contemporary gene flow were higher for T. pallidus than for C. juglandicola. We also found evidence of reciprocal outlier loci in some locations, but none showed significant signatures of selection. Synthesis and applications. Understanding the importance of coevolutionary interactions for the sustainability of biological control remains an important and understudied component of biological control research. Given the observed differences in gene flow and genetic differentiation among populations of T. pallidus and C. juglandicola, we suspect that temporary local disruption of biological control services may occur more frequently than expected while remaining stable at broader regional scales. Further research that combines genomewide single nucleotide polymorphism genotyping with measurements of phenotypic traits is needed to provide more conclusive evidence of whether the occurrence of outlier loci that display significant signatures of selection can be interpreted as evidence of the presence of a geographic mosaic of coevolution in this system.     

Newt Myotubes Reenter the Cell Cycle by Phosphorylation of the Retinoblastoma Protein

Withdrawal from the cell cycle is an essential aspect of vertebrate muscle differentiation and requires the retinoblastoma (Rb) protein that inhibits expression of genes needed for cell cycle entry. It was shown recently that cultured myotubes derived from the Rb^−/−mouse reenter the cell cycle after serum stimulation (Schneider, J.W., W. Gu, L. Zhu, V. Mahdavi, and B. Nadal-Ginard. 1994. Science (Wash. DC). 264:1467– 1471). In contrast with other vertebrates, adult urodele amphibians such as the newt can regenerate their limbs, a process involving cell cycle reentry and local reversal of differentiation. Here we show that myotubes formed in culture from newt limb cells are refractory to several growth factors, but they undergo S phase after serum stimulation and accumulate 4N nuclei. This response to serum is inhibited by contact with mononucleate cells. Despite the phenotypic parallel with Rb^−/− mouse myotubes, Rb is expressed in the newt myotubes, and its phosphorylation via cyclin-dependent kinase 4/6 is required for cell cycle reentry. Thus, the postmitotic arrest of urodele myotubes, although intact in certain respects, can be undermined by a pathway that is inactive in other vertebrates. This may be important for the regenerative ability of these animals.     

Organic dust augments nucleotide-binding oligomerization domain expression via an NF-{kappa}B pathway to negatively regulate inflammatory responses

Nucleotide-binding oligomerization domain 2 (NOD2) is involved in innate immune responses to peptidoglycan degradation products. Peptidoglycans are important mediators of organic dust-induced airway diseases in exposed agriculture workers; however, the role of NOD2 in response to complex organic dust is unknown. Monocytes/macrophages were exposed to swine facility organic dust extract (ODE), whereupon NOD2 expression was evaluated by real-time PCR and Western blot. ODE induced significant NOD2 mRNA and protein expression at 24 and 48 h, respectively, which was mediated via a NF-κB signaling pathway as opposed to a TNF-α autocrine/paracrine mechanism. Specifically, NF-κB translocation increased rapidly following ODE stimulation as demonstrated by EMSA, and inhibition of the NF-κB pathway significantly reduced ODE-induced NOD2 expression. However, there was no significant reduction in ODE-induced NOD2 gene expression when TNF-α was inhibited or absent. Next, it was determined whether NOD2 regulated ODE-induced inflammatory cytokine production. Knockdown of NOD2 expression by small interfering RNA resulted in increased CXCL8 and IL-6, but not TNF-α production in response to ODE. Similarly, primary lung macrophages from NOD2 knockout mice demonstrated increased IL-6, CXCL1, and CXCL1, but not TNF-α, expression. Lastly, a higher degree of airway inflammation occurred in the absence of NOD2 following acute (single) and repetitive (3 wk) ODE exposure in an established in vivo murine model. In summary, ODE-induced NOD2 expression is directly dependent on NF-κB signaling, and NOD2 is a negative regulator of complex, organic dust-induced inflammatory cytokine/chemokine production in mononuclear phagocytes.     

Use of Lactobacillus to prevent infection by pathogenic bacteria

This review focuses on the use and potential of Lactobacillus to prevent infections of the urogenital and intestinal tracts. The presence and dominance of Lactobacillus in the vagina is associated with a reduced risk of bacterial vaginosis and urinary tract infections. The mechanisms appear to involve anti-adhesion factors, by-products such as hydrogen peroxide and bacteriocins lethal to pathogens, and perhaps immune modulation or signaling effects. The instillation of Lactobacillus GR-1 and B-54 or RC-14 strains into the vagina has been shown to reduce the risk of urinary tract infections, and improve the maintenance of a normal flora. Ingestion of these strains into the gut has also been shown to modify the vaginal flora to a more healthy state. In addition, these strains inhibit the growth of intestinal, as well as urogenital pathogens, colonize the gut and protect against infections as shown in mice. Other probiotic strains, such as Lactobacillus GG, have been shown to prevent and treat gastroenteritis caused by rotavirus and bacteria. Given that lactobacilli are not the dominant commensals in a gut which comprises around 10(10) organisms, much work is still needed to define the mechanisms whereby GR-1, RC-14, GG and other strains contribute to health restoration and maintenance. Such critically important studies will require the medical science community to show a willingness to turn away from pharmaceutical remedies as the only solution to health and disease.     

Incentivising fire management in Pindan (Acacia shrubland): A proposed fuel type for Australia's Savanna burning greenhouse gas emissions abatement methodology

The Australian Government has sanctioned development of greenhouse gas emissions (GHG) abatement methodologies to meet international emissions reduction obligations. Savanna burning emissions abatement methodologies have been available since 2012, and there are currently 72 registered projects covering approximately 32 million ha. Abatement to date has exceeded 4 million tonnes of carbon dioxide equivalent (CO2‐e) principally through the application of low intensity early dry season fire management to reduce the amount of biomass combusted in higher intensity late dry season (LDS) fires. Savanna burning projects can only be conducted on areas with eligible fire‐prone vegetation fuel types where implementing the improved fire management regime is considered ecologically appropriate. This study assesses the suitability of including tall Acacia shrublands (‘Pindan’) as a new eligible fuel type. These shrublands make up 12% (~2 million ha) of the Kimberley region, Western Australia, where, on average, 32% is fire affected annually, mostly in the LDS. A standard assessment protocol was applied to describe vegetation fuel type structural and pyrolysis characteristics. We show that Pindan (i) can be identified and mapped as a unique tall Acacia shrubland vegetation fuel type, (ii) characterised by a significantly greater shrubby fuel load biomass, and (iii) the conservation status of which would benefit from imposition of strategic prescribed burning programme. Savanna burning projects in the Pindan fuel type could potentially abate up to 24.43 t.CO₂‐e/km² per year, generating significant income and employment opportunities for predominantly Indigenous land managers in the region.