The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.     

Iota-carrageenan: molecular structure and packing of polysaccharide double helices in oriented fibres of divalent cation salts

The Ca²⁺ and Sr²⁺ salts of i-carrageenan have isomorphous crystal structures with trigonal unit cells of dimensions a = b = 1.373 nm, c = 1.328 nm, γ = 120 °. Two kinds of fibre diffraction pattern were found for the Mg²⁺ salt: one resembling the Ca²⁺ and Sr²⁺ patterns and one with additional layer lines interleaved midway between those in the usual kind of pattern. Specimens of this second type convert to the first type on storage at 92% relative humidity. These Mg²⁺i-carrageenate diffraction patterns provide direct evidence for the double-helical nature of the carrageenan molecule.A molecular model has been derived that consists of two, identical, righthanded, 3-fold helical polysaccharide chains of pitch 2.656 nm. One chain is translated axially 1.32 nm relative to the other.A packing arrangement with up-pointing and down-pointing double helices distributed randomly among the molecular sites explains the presence of both Bragg reflections and layer line streaks. The space group of our statistical crystal structure is P3₂12. The divalent cations were found by Fourier difference syntheses to be at ($\text{2}\text{3}$, $\text{1}\text{3}$, $\text{1}\text{6}$) and symmetry-related positions. The co-ordination of each cation to sulphate groups on two different helices leads to a continuous set of cation-sulphate-cation-… interactions that accounts for the high crystallinity of these salts.The structure of the Ca²⁺ salt has been refined by constrained linked-atom least-squares methods. The structural isomorphism of the Sr²⁺ salt was confirmed by an independent refinement.     

Shared Protein Complex Subunits Contribute to Explaining Disrupted Co-occurrence

The gene composition of present-day genomes has been shaped by a complicated evolutionary history, resulting in diverse distributions of genes across genomes. The pattern of presence and absence of a gene in different genomes is called its phylogenetic profile. It has been shown that proteins whose encoding genes have highly similar profiles tend to be functionally related: As these genes were gained and lost together, their encoded proteins can probably only perform their full function if both are present. However, a large proportion of genes encoding interacting proteins do not have matching profiles. In this study, we analysed one possible reason for this, namely that phylogenetic profiles can be affected by multi-functional proteins such as shared subunits of two or more protein complexes. We found that by considering triplets of proteins, of which one protein is multi-functional, a large fraction of disturbed co-occurrence patterns can be explained.     

Vegetation control effects on untreated wood,crude cellulose and holocellulose δ<Superscript>13</Superscript>C of early and latewood in 3- to 5-year-old rings of Douglas-fir

The stable carbon (C) composition of tree rings expressed as δ¹³C, is a measure of intrinsic water-use efficiency and can indicate the occurrence of past water shortages for tree growth. We examined δ¹³C in 3- to 5-year-old rings of Douglas-fir (Pseudotsuga menziesii (Mirb) Franco) trees to elucidate if decreased water supply or uptake was a critical factor in the observed growth reduction of trees competing with understory herb and shrub vegetation compared to those growing without competition. We hypothesized that there would be no differences in δ¹³C of earlywood in trees growing in plots with competing vegetation and those in plots receiving complete vegetation control during 5 years because earlywood formed early in the growing season when soil water was ample. We also hypothesized that δ¹³C in latewood which was formed during the later half of the growing season when precipitation was low, would be greater (less negative) in trees in plots without vegetation control. We then separated early and latewood from rings for three consecutive years and analyzed their δ¹³C composition. No significant differences in earlywood δ¹³C in years 3–5 were observed for trees in the two vegetation control treatments. δ¹³C of untreated latewood separated from wood cores was greater in 4- and 5-year-old rings of trees growing with competing vegetation compared to trees growing without vegetation competition (i.e., −25.5 vs. −26.3‰ for year 4, and −26.1 vs. −26.8‰ for year 5). Results suggest that water shortages occurred in Douglas-fir trees on this coastal Washington site in the latewood-forming portion of the growing season of years 4 and 5 in the no-vegetation control treatment. We also compared δ¹³C from untreated wood, crude cellulose extracted with the Diglyme–HCl method, and holocellulose extracted with toluene–ethanol to see if the extraction method would increase the sensitivity of the analysis. δ¹³C values from the two extraction methods were highly correlated with those from untreated samples (r ² = 0.97, 0.98, respectively). Therefore, using untreated wood would be as effective as using crude cellulose or holocellulose to investigate δ¹³C patterns in young Douglas-fir.     

Functional Characterization of a Novel Class of Morantel-Sensitive Acetylcholine Receptors in Nematodes

Acetylcholine receptors are pentameric ligand–gated channels involved in excitatory neuro-transmission in both vertebrates and invertebrates. In nematodes, they represent major targets for cholinergic agonist or antagonist anthelmintic drugs. Despite the large diversity of acetylcholine-receptor subunit genes present in nematodes, only a few receptor subtypes have been characterized so far. Interestingly, parasitic nematodes affecting human or animal health possess two closely related members of this gene family, acr-26 and acr-27 that are essentially absent in free-living or plant parasitic species. Using the pathogenic parasitic nematode of ruminants, Haemonchus contortus, as a model, we found that Hco-ACR-26 and Hco-ACR-27 are co-expressed in body muscle cells. We demonstrated that co-expression of Hco-ACR-26 and Hco-ACR-27 in Xenopus laevis oocytes led to the functional expression of an acetylcholine-receptor highly sensitive to the anthelmintics morantel and pyrantel. Importantly we also reported that ACR-26 and ACR-27, from the distantly related parasitic nematode of horses, Parascaris equorum, also formed a functional acetylcholine-receptor highly sensitive to these two drugs. In Caenorhabditis elegans, a free-living model nematode, we demonstrated that heterologous expression of the H. contortus and P. equorum receptors drastically increased its sensitivity to morantel and pyrantel, mirroring the pharmacological properties observed in Xenopus oocytes. Our results are the first to describe significant molecular determinants of a novel class of nematode body wall muscle AChR.     

Benchmarking the Activity,Stability, and Inherent Electrochemistry of Amorphous Molybdenum Sulfide for Hydrogen Production

Anodically electrodeposited amorphous molybdenum sulfide (AE‐MoS_x) has attracted significant attention as a non‐noble metal electrocatalyst for its high activity toward the hydrogen evolution reaction (HER). The [Mo₃S₁₃]^2? polymer‐based structure confers a high density of exposed sulfur moieties, widely regarded as the HER active sites. However, their intrinsic complexity conceals full understanding of their exact role in HER catalysis, hampering their full potential for water splitting applications. In this report, a unifying approach is adopted accounting for modifications in the inherent electrochemistry (EC), HER mechanism, and surface species to maximize the AE‐MoS_x electroactivity over a broad pH region (0–10). Dramatic enhancements in HER performance by selective electrochemical cycling within reductive (overpotential shift, η_HER ≈ ?350 mV) and electro‐oxidative windows (η_HER ≈ ?290 mV) are accompanied by highly stable performance in mildly acidic electrolytes. Joint analysis of X‐ray photoelectron spectroscopy, Raman, and EC experiments corroborate the key role of bridging and terminal S ligands as active site generators at low pH, and reveal molybdenum oxysulfides (Mo⁵⁺O_xS_y) to be the most active HER moiety in AE‐MoS_x in mildly acidic‐to‐neutral environments. These findings will be extremely beneficial for future tailoring of MoS_x materials and their implementation in commercial electrolyzer technologies.     

Towards a Unified Understanding of Event-Related Changes in the EEG: The Firefly Model of Synchronization through Cross-Frequency Phase Modulation

Although event-related potentials (ERPs) are widely used to study sensory, perceptual and cognitive processes, it remains unknown whether they are phase-locked signals superimposed upon the ongoing electroencephalogram (EEG) or result from phase-alignment of the EEG. Previous attempts to discriminate between these hypotheses have been unsuccessful but here a new test is presented based on the prediction that ERPs generated by phase-alignment will be associated with event-related changes in frequency whereas evoked-ERPs will not. Using empirical mode decomposition (EMD), which allows measurement of narrow-band changes in the EEG without predefining frequency bands, evidence was found for transient frequency slowing in recognition memory ERPs but not in simulated data derived from the evoked model. Furthermore, the timing of phase-alignment was frequency dependent with the earliest alignment occurring at high frequencies. Based on these findings, the Firefly model was developed, which proposes that both evoked and induced power changes derive from frequency-dependent phase-alignment of the ongoing EEG. Simulated data derived from the Firefly model provided a close match with empirical data and the model was able to account for i) the shape and timing of ERPs at different scalp sites, ii) the event-related desynchronization in alpha and synchronization in theta, and iii) changes in the power density spectrum from the pre-stimulus baseline to the post-stimulus period. The Firefly Model, therefore, provides not only a unifying account of event-related changes in the EEG but also a possible mechanism for cross-frequency information processing.