Neuroimaging Evidence of Major Morpho-Anatomical and Functional Abnormalities in the BTBR T+TF/J Mouse Model of Autism

BTBR T+tf/J (BTBR) mice display prominent behavioural deficits analogous to the defining symptoms of autism, a feature that has prompted a widespread use of the model in preclinical autism research. Because neuro-behavioural traits are described with respect to reference populations, multiple investigators have examined and described the behaviour of BTBR mice against that exhibited by C57BL/6J (B6), a mouse line characterised by high sociability and low self-grooming. In an attempt to probe the translational relevance of this comparison for autism research, we used Magnetic Resonance Imaging (MRI) to map in both strain multiple morpho-anatomical and functional neuroimaging readouts that have been extensively used in patient populations. Diffusion tensor tractography confirmed previous reports of callosal agenesis and lack of hippocampal commissure in BTBR mice, and revealed a concomitant rostro-caudal reorganisation of major cortical white matter bundles. Intact inter-hemispheric tracts were found in the anterior commissure, ventro-medial thalamus, and in a strain-specific white matter formation located above the third ventricle. BTBR also exhibited decreased fronto-cortical, occipital and thalamic gray matter volume and widespread reductions in cortical thickness with respect to control B6 mice. Foci of increased gray matter volume and thickness were observed in the medial prefrontal and insular cortex. Mapping of resting-state brain activity using cerebral blood volume weighted fMRI revealed reduced cortico-thalamic function together with foci of increased activity in the hypothalamus and dorsal hippocampus of BTBR mice. Collectively, our results show pronounced functional and structural abnormalities in the brain of BTBR mice with respect to control B6 mice. The large and widespread white and gray matter abnormalities observed do not appear to be representative of the neuroanatomical alterations typically observed in autistic patients. The presence of reduced fronto-cortical metabolism is of potential translational relevance, as this feature recapitulates previously-reported clinical observations

The Molecular Biogeography of the Indo-Pacific: Testing Hypotheses With Multispecies Genetic Patterns

Aim: To test hypothesized biogeographic partitions of the tropical Indo-Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test. \u3eLocation: The Indo-Pacific Ocean. Time Period: Pliocene through the Holocene. Major Taxa Studied: Fifty-six marine species. Methods: We tested eight biogeographic hypotheses for partitioning of the Indo-Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance-based redundancy analysis (dbRDA). Results: We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance. Main Conclusions: Although there is support for three previously described barriers, phylogeographic discordance in the Indo-Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo-Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5

Improvement to the Prediction of Fuel Cost Distributions Using ARIMA Model

Availability of a validated, realistic fuel cost model is a prerequisite to the development and validation of new optimization methods and control tools. This paper uses an autoregressive integrated moving average (ARIMA) model with historical fuel cost data in development of a three-step-ahead fuel cost distribution prediction. First, the data features of Form EIA-923 are explored and the natural gas fuel costs of Texas generating facilities are used to develop and validate the forecasting algorithm for the Texas example. Furthermore, the spot price associated with the natural gas hub in Texas is utilized to enhance the fuel cost prediction. The forecasted data is fit to a normal distribution and the Kullback-Leibler divergence is employed to evaluate the difference between the real fuel cost distributions and the estimated distributions. The comparative evaluation suggests the proposed forecasting algorithm is effective in general and is worth pursuing further.Comment: Accepted by IEEE PES 2018 General Meetin

Optimized Expression and Purification for High-Activity Preparations of Algal [FeFe]-Hydrogenase

Background: Recombinant expression and purification of metallo-enzymes, including hydrogenases, at high-yields is challenging due to complex, and enzyme specific, post-translational maturation processes. Low fidelities of maturation result in preparations containing a significant fraction of inactive, apo-protein that are not suitable for biophysical or crystallographic studies. Principal Findings: We describe the construction, overexpression and high-yield purification of a fusion protein consisting of the algal [2Fe2S]-ferredoxin PetF (Fd) and [FeFe]-hydrogenase HydA1. The maturation of Fd-HydA1 was optimized through improvements in culture conditions and media components used for expression. We also demonstrated that fusion of Fd to the N-terminus of HydA1, in comparison to the C-terminus, led to increased expression levels that were 4-fold higher. Together, these improvements led to enhanced HydA1 activity and improved yield after purification. The strong binding-affinity of Fd for DEAE allowed for two-step purification by ion exchange and StrepTactin affinity chromatography. In addition, the incorporation of a TEV protease site in the Fd-HydA1 linker allowed for the proteolytic removal of Fd after DEAE step, and purification of HydA1 alone by StrepTactin. In combination, this process resulted in HydA1 purification yields of 5 mg L−1 of culture from E. coli with specific activities of 1000 U (U = 1 µmol hydrogen evolved mg−1 min−1). Significance: The [FeFe]-hydrogenases are highly efficient enzymes and their catalytic sites provide model structures for synthetic efforts to develop robust hydrogen activation catalysts. In order to characterize their structure-function properties in greater detail, and to use hydrogenases for biotechnological applications, reliable methods for rapid, high-yield expression and purification are required.United States. Dept. of Energy. (contract DE-AC36-08-GO28308

The molecular biogeography of the Indo‐Pacific: Testing hypotheses with multispecies genetic patterns

Aim: To test hypothesized biogeographic partitions of the tropical Indo‐Pacific Ocean with phylogeographic data from 56 taxa, and to evaluate the strength and nature of barriers emerging from this test. Location: The Indo‐Pacific Ocean. Time period: Pliocene through the Holocene. Major taxa studied: Fifty‐six marine species. Methods: We tested eight biogeographic hypotheses for partitioning of the Indo‐ Pacific using a novel modification to analysis of molecular variance. Putative barriers to gene flow emerging from this analysis were evaluated for pairwise ΦST, and these ΦST distributions were compared to distributions from randomized datasets and simple coalescent simulations of vicariance arising from the Last Glacial Maximum. We then weighed the relative contribution of distance versus environmental or geographic barriers to pairwise ΦST with a distance‐based redundancy analysis (dbRDA). Results: We observed a diversity of outcomes, although the majority of species fit a few broad biogeographic regions. Repeated coalescent simulation of a simple vicariance model yielded a wide distribution of pairwise ΦST that was very similar to empirical distributions observed across five putative barriers to gene flow. Three of these barriers had median ΦST that were significantly larger than random expectation. Only 21 of 52 species analysed with dbRDA rejected the null model. Among these, 15 had overwater distance as a significant predictor of pairwise ΦST, while 11 were significant for geographic or environmental barriers other than distance. Main conclusions: Although there is support for three previously described barriers, phylogeographic discordance in the Indo‐Pacific Ocean indicates incongruity between processes shaping the distributions of diversity at the species and population levels. Among the many possible causes of this incongruity, genetic drift provides the most compelling explanation: given massive effective population sizes of Indo‐Pacific species, even hard vicariance for tens of thousands of years can yield ΦST values that range from 0 to nearly 0.5

Developing User‐Friendly Habitat Suitability Tools from Regional Stream Fish Survey Data

We developed user‐friendly fish habitat suitability tools (plots) for fishery managers in Michigan; these tools are based on driving habitat variables and fish population estimates for several hundred stream sites throughout the state. We generated contour plots to show patterns in fish biomass for over 60 common species (and for 120 species grouped at the family level) in relation to axes of catchment area and low‐flow yield (90% exceedance flow divided by catchment area) and also in relation to axes of mean and weekly range of July temperatures. The plots showed distinct patterns in fish habitat suitability at each level of biological organization studied and were useful for quantitatively comparing river sites. We demonstrate how these plots can be used to support stream management, and we provide examples pertaining to resource assessment, trout stocking, angling regulations, chemical reclamation of marginal trout streams, indicator species, instream flow protection, and habitat restoration. These straightforward and effective tools are electronically available so that managers can easily access and incorporate them into decision protocols and presentations.Received April 9, 2010; accepted November 8, 2010Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/141005/1/nafm0041.pd

Investigating Effects of Tulathromycin Metaphylaxis on the Fecal Resistome and Microbiome of Commercial Feedlot Cattle Early in the Feeding Period

The objective was to examine effects of treating commercial beef feedlot cattle with therapeutic doses of tulathromycin, a macrolide antimicrobial drug, on changes in the fecal resistome and microbiome using shotgun metagenomic sequencing. Two pens of cattle were used, with all cattle in one pen receiving metaphylaxis treatment (800 mg subcutaneous tulathromycin) at arrival to the feedlot, and all cattle in the other pen remaining unexposed to parenteral antibiotics throughout the study period. Fecal samples were collected from 15 selected cattle in each group just prior to treatment (Day 1), and again 11 days later (Day 11). Shotgun sequencing was performed on isolated metagenomic DNA, and reads were aligned to a resistance and a taxonomic database to identify alignments to antimicrobial resistance (AMR) gene accessions and microbiome content. Overall, we identified AMR genes accessions encompassing 9 classes of AMR drugs and encoding 24 unique AMR mechanisms. Statistical analysis was used to identify differences in the resistome and microbiome between the untreated and treated groups at both timepoints, as well as over time. Based on composition and ordination analyses, the resistome and microbiome were not significantly different between the two groups on Day 1 or on Day 11. However, both the resistome and microbiome changed significantly between these two sampling dates. These results indicate that the transition into the feedlot—and associated changes in diet, geography, conspecific exposure, and environment—may exert a greater influence over the fecal resistome and microbiome of feedlot cattle than common metaphylactic antimicrobial drug treatment

Human Pathogen Shown to Cause Disease in the Threatened Eklhorn Coral Acropora palmata

Coral reefs are in severe decline. Infections by the human pathogen Serratia marcescens have contributed to precipitous losses in the common Caribbean elkhorn coral, Acropora palmata, culminating in its listing under the United States Endangered Species Act. During a 2003 outbreak of this coral disease, called acroporid serratiosis (APS), a unique strain of the pathogen, Serratia marcescens strain PDR60, was identified from diseased A. palmata, human wastewater, the non-host coral Siderastrea siderea and the corallivorous snail Coralliophila abbreviata. In order to examine humans as a source and other marine invertebrates as vectors and/or reservoirs of the APS pathogen, challenge experiments were conducted with A. palmata maintained in closed aquaria to determine infectivity of strain PDR60 from reef and wastewater sources. Strain PDR60 from wastewater and diseased A. palmata caused disease signs in elkhorn coral in as little as four and five days, respectively, demonstrating that wastewater is a definitive source of APS and identifying human strain PDR60 as a coral pathogen through fulfillment of Koch's postulates. A. palmata inoculated with strain PDR60 from C. abbreviata showed limited virulence, with one of three inoculated fragments developing APS signs within 13 days. Strain PDR60 from non-host coral S. siderea showed a delayed pathogenic effect, with disease signs developing within an average of 20 days. These results suggest that C. abbreviata and non-host corals may function as reservoirs or vectors of the APS pathogen. Our results provide the first example of a marine “reverse zoonosis” involving the transmission of a human pathogen (S. marcescens) to a marine invertebrate (A. palmata). These findings underscore the interaction between public health practices and environmental health indices such as coral reef survival