The brain is getting ready for dinner

Every evening, as we get ready for dinner, in addition to the routine behaviors of preparing the meal itself, we also prepare our bodies to cope with the upcoming meal. This could take the form of making restaurant reservations, changing into appropriate attire, washing hands, priming ourselves with an aperitif, or even consciously avoiding snacks as the meal approaches. A study by Johnstone and colleagues in this issue of Cell Metabolism (Johnstone et al., 2006) provides evidence that in parallel to our learned preparatory behaviors, our central nervous system is going through comparable motions as it gets ready for the anticipated meal.     

Primary cilia and forebrain development

With a microtubule-based axoneme supporting its plasma membrane-ensheathed projection from the basal body of almost all cell types in the human body, and present in only one copy per cell, the primary cilium can be considered an organelle sui generis. Although it was first observed and recorded in histological studies from the late 19th century, the tiny structure was essentially forgotten for many decades. In the past ten years, however, scientists have turned their eyes once again upon primary cilia and realized that they are very important for the development of almost all organs in the mammalian body, especially those dependent upon the signaling from members Hedgehog family, such as Indian and Sonic hedgehog. In this review, we outline the roles that primary cilia play in forebrain development, not just in the crucial transduction of Sonic hedgehog signaling, but also new results showing that cilia are important for cell cycle progression in proliferating neural precursors. We will focus upon cerebral cortex development but will also discuss the importance of cilia for the embryonic hippocampus, olfactory bulb, and diencephalon.     

Biomass and Total Lipid Content Assessment of Microalgal Cultures Using Near and Short Wave Infrared Spectroscopy

The technique of near and short wave near-infrared spectroscopy was assessed with respect to analysis of dry matter and lipid content of microalgae with potential for biodiesel production. Microalgal culture samples were filtered through GF/C filter papers and spectral measurements of wet and oven dried (60 °C overnight) filter papers over the ranges of 300–1,100 nm and 1,100–2,500 nm were recorded. Partial least square models on culture biomass and lipid content for combined species data were poor in terms of RMSECV, R _CV and the ratio of RMSECV to SD. A single species model for C. vulgaris based on 1,100–2,500 nm spectra of dry filtrate supported a model with RMSECV, R _CV and SDR values of 0.32 g L^?1, 0.955 and 3.38 for biomass and 0.089 g L^?1, 0.874 and 2.06 with lipid, respectively. However, the dry filtrate models on biomass and lipid content performed poorly in the prediction of samples drawn from an independent series of C. vulgaris cultured under N-, P- and Fe-limited growth trial. Thus, while the near-infrared spectroscopy technique has potential for assessment of dry matter and lipid content of microalgal cultures using a dried filtrate sample, further work is required to examine the limits to model robustness.     

Auditory Attention Activates Peripheral Visual Cortex

Background

Recent neuroimaging studies have revealed that putatively unimodal regions of visual cortex can be activated during auditory tasks in sighted as well as in blind subjects. However, the task determinants and functional significance of auditory occipital activations (AOAs) remains unclear.

Methodology/Principal Findings

We examined AOAs in an intermodal selective attention task to distinguish whether they were stimulus-bound or recruited by higher-level cognitive operations associated with auditory attention. Cortical surface mapping showed that auditory occipital activations were localized to retinotopic visual cortex subserving the far peripheral visual field. AOAs depended strictly on the sustained engagement of auditory attention and were enhanced in more difficult listening conditions. In contrast, unattended sounds produced no AOAs regardless of their intensity, spatial location, or frequency.

Conclusions/Significance

Auditory attention, but not passive exposure to sounds, routinely activated peripheral regions of visual cortex when subjects attended to sound sources outside the visual field. Functional connections between auditory cortex and visual cortex subserving the peripheral visual field appear to underlie the generation of AOAs, which may reflect the priming of visual regions to process soon-to-appear objects associated with unseen sound sources.     

Metabolomic Derangements Are Associated with Mortality in Critically Ill Adult Patients

Objective

To identify metabolomic biomarkers predictive of Intensive Care Unit (ICU) mortality in adults.

Rationale

Comprehensive metabolomic profiling of plasma at ICU admission to identify biomarkers associated with mortality has recently become feasible.

Methods

We performed metabolomic profiling of plasma from 90 ICU subjects enrolled in the BWH Registry of Critical Illness (RoCI). We tested individual metabolites and a Bayesian Network of metabolites for association with 28-day mortality, using logistic regression in R, and the CGBayesNets Package in MATLAB. Both individual metabolites and the network were tested for replication in an independent cohort of 149 adults enrolled in the Community Acquired Pneumonia and Sepsis Outcome Diagnostics (CAPSOD) study.

Results

We tested variable metabolites for association with 28-day mortality. In RoCI, nearly one third of metabolites differed among ICU survivors versus those who died by day 28 (N = 57 metabolites, p<.05). Associations with 28-day mortality replicated for 31 of these metabolites (with p<.05) in the CAPSOD population. Replicating metabolites included lipids (N = 14), amino acids or amino acid breakdown products (N = 12), carbohydrates (N = 1), nucleotides (N = 3), and 1 peptide. Among 31 replicated metabolites, 25 were higher in subjects who progressed to die; all 6 metabolites that are lower in those who die are lipids. We used Bayesian modeling to form a metabolomic network of 7 metabolites associated with death (gamma-glutamylphenylalanine, gamma-glutamyltyrosine, 1-arachidonoylGPC(20:4), taurochenodeoxycholate, 3-(4-hydroxyphenyl) lactate, sucrose, kynurenine). This network achieved a 91% AUC predicting 28-day mortality in RoCI, and 74% of the AUC in CAPSOD (p<.001 in both populations).

Conclusion

Both individual metabolites and a metabolomic network were associated with 28-day mortality in two independent cohorts. Metabolomic profiling represents a valuable new approach for identifying novel biomarkers in critically ill patients.     

Risk assessment for engineered bacteria used in biocontrol of fungal disease in agricultural crops

A plant growth promoting rhizobacterium (PGPR)Pseudomonas fluorescens SBW25 (WT) protects a number of crop plant species from damping-off caused by Pythium ultimum. A genetically modified, phenazine-1-carboxylic acid (PCA) producing variant, 23.10, carries on its chromosome a single copy of phzABCDEFG, under the control of the P tac constitutive promoter. The genetically modified biological control agent (GM-BCA), 23.10, has improved biocontrol activity when compared to wild type SBW25, and can effectively suppress Pythium spp. present at up to 100 times normal field infestations. GM-BCA inocula establish high population densities which persist well in the phytosphere of several crop plants including pea, wheat and sugar beet, effectively suppressed infection and promoted increase in total plant biomass. It also has an improved spectrum of activity over other plant phytopathogens such as Fusarium spp. Gaeumannomyces graminis var. tritici, Phytophtora cinnamomi and Rhizoctonia solani. However in developing BCAs and in particular GMBCAs it is important to determine whether their use has any adverse effect in the environment. Any observed changes following inoculation with wild type BCA or GM BCA in microbial diversity (bacteria and fungi) were negligible when assessed by either quantitive selective plate count methods (CFU/g) or culture independent molecular assays (SSU rRNA based PCR-DGGE). Rhizosphere community diversity profiles (DGGE) in infected plants in the presence of inocula were highly similar to disease free systems. Histological assessment of the impact of inocula on established functional mycorrhizae associations were conducted on cores collected from an established field margin grassland pasture. No adverse impact on mycorrhizal colonization and root infection were recorded after addition of WT or GM-BCA bacterial inocula as a soil drench. This approach and the related culturable and culture independent methods have recorded only a minor, transient perturbation to microbial communities, but as far as we are aware this is the first direct demonstration that a functional, AFC producing GMM also has only a transient impact on mycorrhizal associations in established plant communities. In all instances studied the plant species, plant stage of development and disease, damping-off, had a greater impact on changes in rhizosphere diversity than the presence of an introduced GM bacterial inocula.     

Multilocus genotyping and molecular phylogenetics resolve a novel head blight pathogen within the Fusarium graminearum species complex from Ethiopia

A survey of Fusarium head blight (FHB)-contaminated wheat in Ethiopia recovered 31 isolates resembling members of the Fusarium graminearum species complex. Results of a multilocus genotyping (MLGT) assay for FHB species and trichothecene chemotype determination suggested that 22 of these isolates might represent a new species within the Fg complex. Phylogenetic analyses of multilocus DNA sequence data resolved the 22 Ethiopian isolates as a novel, phylogenetically distinct species. The new species also appears to be novel in that MLGT probe data and sequence analysis of both ends of the TRI-cluster identified 15ADON and NIV recombination blocks, documenting inter-chemotype recombination involving the chemotype-determining genes near the ends of the TRI-cluster. Results of pathogenicity experiments and analyses of trichothecene mycotoxins demonstrated that this novel Fg complex species could induce FHB on wheat and elaborate 15ADON in planta. Herein the FHB pathogen from Ethiopia is formally described as a novel species.     

LKB1 is required for hepatic bile acid transport and canalicular membrane integrity in mice

LKB1 is a 'master' protein kinase implicated in the regulation of metabolism, cell proliferation, cell polarity and tumorigenesis. However, the long-term role of LKB1 in hepatic function is unknown. In the present study, it is shown that hepatic LKB1 plays a key role in liver cellular architecture and metabolism. We report that liver-specific deletion of LKB1 in mice leads to defective canaliculi and bile duct formation, causing impaired bile acid clearance and subsequent accumulation of bile acids in serum and liver. Concomitant with this, it was found that the majority of BSEP (bile salt export pump) was retained in intracellular pools rather than localized to the canalicular membrane in hepatocytes from LLKB1KO (liver-specific Lkb1-knockout) mice. Together, these changes resulted in toxic accumulation of bile salts, reduced liver function and failure to thrive. Additionally, circulating LDL (low-density lipoprotein)-cholesterol and non-esterified cholesterol levels were increased in LLKB1KO mice with an associated alteration in red blood cell morphology and development of hyperbilirubinaemia. These results indicate that LKB1 plays a critical role in bile acid homoeostasis and that lack of LKB1 in the liver results in cholestasis. These findings indicate a novel key role for LKB1 in the development of hepatic morphology and membrane targeting of canalicular proteins.