Diets of giants: the nutritional value of sauropod diet during the Mesozoic

A major uncertainty in estimating energy budgets and population densities of extinct animals is the carrying capacity of their ecosystems, constrained by net primary productivity (NPP) and its digestible energy content. The hypothesis that increases in NPP due to elevated atmospheric CO₂ contributed to the unparalleled size of the sauropods has recently been rejected, based on modern studies on herbivorous insects that imply a general, negative correlation of diet quality and increasing CO₂. However, the nutritional value of plants grown under elevated CO₂ levels might be very different for vertebrate megaherbivores than for insects. Here we show plant species‐specific responses in metabolizable energy and nitrogen content, equivalent to a two‐fold variation in daily food intake estimates for a typical sauropod, for dinosaur food plant analogues grown under CO₂ concentrations spanning estimates for Mesozoic atmospheric concentrations. Our results potentially rebut the hypothesis that constraints on sauropod diet quality were driven by Mesozoic CO₂ concentration.     

Structure and Functional Characterization of Human Histidine Triad Nucleotide-Binding Protein 1 Mutations Associated with Inherited Axonal Neuropathy with Neuromyotonia

Inherited peripheral neuropathies are a group of neurodegenerative disorders that clinically affect 1 in 2500 individuals. Recently, genetic mutations in human histidine nucleotide-binding protein 1 (hHint1) have been strongly and most frequently associated with patients suffering from axonal neuropathy with neuromyotonia. However, the correlation between the impact of these mutations on the hHint1 structure, enzymatic activity and in vivo function has remained ambiguous. Here, we provide detailed biochemical characterization of a set of these hHint1 mutations. Our findings indicate that half of the mutations (R37P, G93D and W123*) resulted in a destabilization of the dimeric state and a significant decrease in catalytic activity and HINT1 inhibitor binding affinity. The H112N mutant was found to be dimeric, but devoid of catalytic activity, due to the loss of the catalytically essential histidine; nevertheless, it exhibited high affinity to AMP and a HINT1 inhibitor. In contrast to the active-site mutants, the catalytic activity and dimeric structure of the surface mutants, C84R and G89V, were found to be similar to the wild-type enzyme. Taken together, our results suggest that the pathophysiology of inherited axonal neuropathy with neuromyotonia can be induced by conversion of HINT1 from a homodimer to monomer, by modification of select surface residues or by a significant reduction of the enzyme's catalytic efficiency.     

Targeted metabolomic profiling of low and high grade serous epithelial ovarian cancer tissues: a pilot study

Introduction

Epithelial ovarian cancer (EOC) remains the leading cause of death from gynecologic malignancies and has an alarming global fatality rate. Besides the differences in underlying pathogenesis, distinguishing between high grade (HG) and low grade (LG) EOC is imperative for the prediction of disease progression and responsiveness to chemotherapy.

Objectives

The aim of this study was to investigate, the tissue metabolome associated with HG and LG serous epithelial ovarian cancer.

Methods

A combination of one dimensional proton nuclear magnetic resonance (1D H NMR) spectroscopy and targeted mass spectrometry (MS) was employed to profile the tissue metabolome of HG, LG serous EOCs, and controls.

Results

Using partial least squares-discriminant analysis, we observed significant separation between all groups (p?<?0.05) following cross validation. We identified which metabolites were significantly perturbed in each EOC grade as compared with controls and report the biochemical pathways which were perturbed due to the disease. Among these metabolic pathways, ascorbate and aldarate metabolism was identified, for the first time, as being significantly altered in both LG and HG serous cancers. Further, we have identified potential biomarkers of EOC and generated predictive algorithms with AUC (CI)?=?0.940 and 0.929 for HG and LG, respectively.

Conclusion

These previously unreported biochemical changes provide a framework for future metabolomic studies for the development of EOC biomarkers. Finally, pharmacologic targeting of the key metabolic pathways identified herein could lead to novel and effective treatments of EOC.

     

Landscape host abundance and configuration regulate periodic outbreak behavior in spruce budworm Choristoneura fumiferana

Landscape‐level forest management has long been hypothesized to affect forest insect outbreak dynamics, but empirical evidence remains elusive. We hypothesized that the combination of increased hardwood relative to host tree species, prevalence of younger forests, and fragmentation of those forests due to forest harvesting legacies would reduce outbreak intensity, increase outbreak frequency, and decrease spatial synchrony in spruce budworm Choristoneura fumiferana outbreaks. We investigated these hypotheses using tree ring samples collected across 51 sites pooled into 16 subareas distributed across a large ecoregion spanning the international border between Ontario (Canada), and Minnesota (USA). This ecoregion contains contrasting land management zones with clear differences in forest landscape structure (i.e. forest composition and spatial configuration) while minimizing the confounding influence of climate. Cluster analyses of the 76‐yr time‐series generally grouped by subareas found within the same land management zone. Spatial nonparametric covariance analysis indicated that the highest and lowest degree of spatial synchrony of spruce budworm outbreaks were found within unmanaged wilderness and lands managed at fine spatial scales in Minnesota, respectively. Using multivariate analysis, we also found that forest composition, configuration, and climate together accounted for a total of 40% of the variance in outbreak chronologies, with a high level of shared variance between composition and configuration (13%) and between composition and climate (9%). At the scale of our study, climate on its own did not explain any of the spatial variation in outbreaks. Outbreaks were of higher frequency, lower intensity, and less spatially synchronized in more fragmented, younger forests with a lower proportion of host species, with opposing outbreak characteristics observed in regions characterised by older forests with more concentrated host species. Our study is the first quantitative evaluation of the long‐standing ‘silvicultural hypothesis’ of spruce budworm management specifically conducted at a spatio‐temporal scale for which it was intended.     

Investigation into the intracellular fates,speciation and mode of action of selenium-containing neuroprotective agents using XAS and XFM

Background

A variety of selenium compounds have been observed to provide protection against oxidative stress, presumably by mimicking the mechanism of action of the glutathione peroxidases. However, the selenium chemistry that underpins the action of these compounds has not been unequivocally established.

Progress in Definition,Prevention and Treatment of Fungal Infections in Cystic Fibrosis

Cystic fibrosis (CF) is a chronic lethal multi-system condition; however, most of the morbidity and mortality is dependent on the status of the respiratory system. Progressive respiratory decline is mediated by chronic infection and inflammation, punctuated by important acute events known as pulmonary exacerbations which can lead to accelerated decline. The main bacterial species causing infections include Pseudomonas aeruginosa, Staphylococcus aureus, Haemophilus influenzae and Achromobacter xylosoxidans. In addition to bacteria, fungi are detected in a significant number of patients. The impact of fungal colonization of the airways is still not completely elucidated, but an increasing body of evidence suggests an important role for moulds and yeasts. Although fungal infections are rare, fungi can cause severe pneumonia requiring appropriate targeted treatment. The most common fungi in respiratory samples of patients with CF are Aspergillus fumigatus, Aspergillus terreus and Scedosporium species for filamentous fungi, and yeasts such as Candida albicans and Candida glabrata. Therapeutic strategies depend on the detected fungus and the underlying clinical status of the patient. The antifungal therapy can range from a simple monotherapy up to a combination of three different drugs. Treatment course may be indicated in some patients for two weeks and in others for up to six months, and in rare cases even longer. New antifungal drugs have been developed and are being tested in clinical studies offering the hope of therapeutic alternatives to existing drugs. Identifying relevant risk factors and diagnostic criteria for fungal colonization and infection is crucial to enabling an adequate prevention, diagnosis and treatment.     

Investigating species boundaries using DNA and morphology in the mite <Emphasis Type="Italic">Tyrophagus curvipenis</Emphasis> (Acari: Acaridae), an emerging invasive pest,with a molecular phylogeny of the genus <Emphasis Type="Italic">Tyrophagus</Emphasis>

Mites of the genus Tyrophagus (Acari: Acaridae) are among the most widespread and common mites, inhabiting diverse natural and anthropogenic habitats. Some species are pests of agricultural products and stored food and/or live in house dust, causing allergies to humans. We sequenced 1.2 kb of the mitochondrial COI gene for 38 individuals belonging to seven species of Tyrophagus, including T. curvipenis, T. putrescentiae, T. fanetzhangorum, T. longior, T. perniciosus, and T. cf. similis. Molecular phylogenetic analyses (1) recovered two major clades corresponding to the presence or absence of eyespots, and (2) separated all included morphological species. Tyrophagus curvipenis and T. putrescentiae had the lowest between-species genetic distances (range, mean?±?SD): 14.20–16.30, 15.17?±?0.40 (K2P). The highest within-species variation was found in T. putrescentiae 0.00–4.33, 1.78?±?1.44 (K2P). In this species, we recovered two distinct groups; however, no geographical or ecological dissimilarities were observed between them. Based on our analyses, we document important morphological differences between T. curvipenis and T. putrescentiae. For the first time, we record the occurrence of T. curvipenis in the New World and suggest that it may be an emerging pest as it is currently spreading in agricultural produce.     

ProtaBank: A repository for protein design and engineering data

We present ProtaBank, a repository for storing, querying, analyzing, and sharing protein design and engineering data in an actively maintained and updated database. ProtaBank provides a format to describe and compare all types of protein mutational data, spanning a wide range of properties and techniques. It features a user‐friendly web interface and programming layer that streamlines data deposition and allows for batch input and queries. The database schema design incorporates a standard format for reporting protein sequences and experimental data that facilitates comparison of results across different data sets. A suite of analysis and visualization tools are provided to facilitate discovery, to guide future designs, and to benchmark and train new predictive tools and algorithms. ProtaBank will provide a valuable resource to the protein engineering community by storing and safeguarding newly generated data, allowing for fast searching and identification of relevant data from the existing literature, and exploring correlations between disparate data sets. ProtaBank invites researchers to contribute data to the database to make it accessible for search and analysis. ProtaBank is available at https://protabank.org .     

Identification of trehalose as a compatible solute in different species of acidophilic bacteria

The major industrial heap bioleaching processes are located in desert regions (mainly Chile and Australia) where fresh water is scarce and the use of resources with low water activity becomes an attractive alternative. However, in spite of the importance of the microbial populations involved in these processes, little is known about their response or adaptation to osmotic stress. In order to investigate the response to osmotic stress in these microorganisms, six species of acidophilic bacteria were grown at elevated osmotic strength in liquid media, and the compatible solutes synthesised were identified using ion chromatography and MALDI-TOF mass spectrometry. Trehalose was identified as one of, or the sole, compatible solute in all species and strains, apart from Acidithiobacillus thiooxidans where glucose and proline levels increased at elevated osmotic potentials. Several other potential compatible solutes were tentatively identified by MALDITOF analysis. The same compatible solutes were produced by these bacteria regardless of the salt used to produce the osmotic stress. The results correlate with data from sequenced genomes which confirm that many chemolithotrophic and heterotrophic acidophiles possess genes for trehalose synthesis. This is the first report to identify and quantify compatible solutes in acidophilic bacteria that have important roles in biomining technologies.