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Experiments using controlled manipulation of climate variables in the field are critical for developing and testing mechanistic models of ecosystem responses to climate change. Despite rapid changes in climate observed in many high latitude and high altitude environments, controlled manipulations in these remote regions have largely been limited to passive experimental methods with variable effects on environmental factors. In this study, we tested a method of controlled soil warming suitable for remote field locations that can be powered using alternative energy sources. The design was tested in high latitude, alpine tundra of southern Yukon Territory, Canada, in 2010 and 2011. Electrical warming probes were inserted vertically in the near-surface soil and powered with photovoltaics attached to a monitoring and control system. The warming manipulation achieved a stable target warming of 1.3 to 2 °C in 1 m(2) plots while minimizing disturbance to soil and vegetation. Active control of power output in the warming plots allowed the treatment to closely match spatial and temporal variations in soil temperature while optimizing system performance during periods of low power supply. Active soil heating with vertical electric probes powered by alternative energy is a viable option for remote sites and presents a low-disturbance option for soil warming experiments. This active heating design provides a valuable tool for examining the impacts of soil warming on ecosystem processes.

Caribou are an integral component of high-latitude ecosystems and represent a major subsistence food source for many northern people. The availability and quality of winter habitat is critical to sustain these caribou populations. Caribou commonly use older spruce woodlands with adequate terrestrial lichen, a preferred winter forage, in the understory. Changes in climate and fire regime pose a significant threat to the long-term sustainability of this important winter habitat. Computer simulations performed with a spatially explicit vegetation succession model (ALFRESCO) indicate that changes in the frequency and extent of fire in interior Alaska may substantially impact the abundance and quality of winter habitat for caribou. We modeled four different fire scenarios and tracked the frequency, extent, and spatial distribution of the simulated fires and associated changes to vegetation composition and distribution. Our results suggest that shorter fire frequencies (i.e., less time between recurring fires) on the winter range of the Nelchina caribou herd in eastern interior Alaska will result in large decreases of available winter habitat, relative to that currently available, in both the short and long term. A 30% shortening of the fire frequency resulted in a 3.5-fold increase in the area burned annually and an associated 41% decrease in the amount of spruce-lichen forest found on the landscape. More importantly, simulations with more frequent fires produced a relatively immature forest age structure, compared to that which currently exists, with few stands older than 100 years. This age structure is at the lower limits of stand age classes preferred by caribou from the Nelchina herd. Projected changes in fire regime due to climate warming and/or additional prescribed burning could substantially alter the winter habitat of caribou in interior Alaska and lead to changes in winter range use and/or population dynamics.

Experiments using controlled manipulation of climate variables in the field are critical for developing and testing mechanistic models of ecosystem responses to climate change. Despite rapid changes in climate observed in many high latitude and high altitude environments, controlled manipulations in these remote regions have largely been limited to passive experimental methods with variable effects on environmental factors. In this study, we tested a method of controlled soil warming suitable for remote field locations that can be powered using alternative energy sources. The design was tested in high latitude, alpine tundra of southern Yukon Territory, Canada, in 2010 and 2011. Electrical warming probes were inserted vertically in the near-surface soil and powered with photovoltaics attached to a monitoring and control system. The warming manipulation achieved a stable target warming of 1.3 to 2 degree C in 1 m2 plots while minimizing disturbance to soil and vegetation. Active control of power output in the warming plots allowed the treatment to closely match spatial and temporal variations in soil temperature while optimizing system performance during periods of low power supply. Active soil heating with vertical electric probes powered by alternative energy is a viable option for remote sites and presents a low-disturbance option for soil warming experiments. This active heating design provides a valuable tool for examining the impacts of soil warming on ecosystem processes.

Magnetic resonance imaging (MRI) of transgenic mice has the potential to provide valuable insight into the complex mechanisms underlying Alzheimer's disease (AD). Quantification of pathological changes is typically performed using manual segmentation methods, and requires a priori hypotheses about anatomical structures for volumetric measurement. Alternatively, deformation-based morphometry (DBM) has been shown to be a powerful, automated technique for detecting anatomical differences between populations by examining the deformation fields used to nonlinearly warp MR images. In this multiple timepoint, in vivo study, we have applied an automated, unbiased technique for the creation of a nonlinear, population-specific reference space from which robust DBM analysis can be performed. A general, linear mixed-effects model framework was developed to follow the evolution of structural changes in mouse brain from 2.5 to 9 months of age, and to examine neuroanatomical differences between a transgenic (TG) APP/PS1 murine model of AD and wild-type (WT) littermates. Morphometric abnormalities in the TG group were localized to regions of the hippocampus, cortex, olfactory bulbs, stria terminalis, brain stem, cerebellum, and ventricles. Although volumetric reductions were detected in TG mice, no general brain atrophy was found, suggesting a developmental, rather than a degenerative, pathological process. Finally, we established a strong correlation between a DBM summary measure and manually segmented volumes for each image in the dataset. These results support the utility of DBM to study longitudinal morphological changes in mouse models of central nervous system diseases in an automated and exploratory fashion.

The ability to visualize behaviourally evoked neural activity patterns across the rodent brain is essential for understanding the distributed brain networks mediating particular behaviours. However, current imaging methods are limited in their spatial resolution and/or ability to obtain brain-wide coverage of functional activity. Here, we describe a new automated method for obtaining cellular-level, whole-brain maps of behaviourally induced neural activity in the mouse. This method combines the use of transgenic immediate-early gene reporter mice to visualize neural activity; serial two-photon tomography to image the entire brain at cellular resolution; advanced image processing algorithms to count the activated neurons and align the datasets to the Allen Mouse Brain Atlas; and statistical analysis to identify the network of activated brain regions evoked by behaviour. We demonstrate the use of this approach to determine the whole-brain networks activated during the retrieval of fear memories. Consistent with previous studies, we identified a large network of amygdalar, hippocampal, and neocortical brain regions implicated in fear memory retrieval. Our proposed methods can thus be used to map cellular networks involved in the expression of normal behaviours as well as to investigate in depth circuit dysfunction in mouse models of neurobiological disease.

Approximately one-third of all mammalian genes are essential for life. Phenotypes resulting from knockouts of these genes in mice have provided tremendous insight into gene function and congenital disorders. As part of the International Mouse Phenotyping Consortium effort to generate and phenotypically characterize 5,000 knockout mouse lines, here we identify 410 lethal genes during the production of the first 1,751 unique gene knockouts. Using a standardized phenotyping platform that incorporates high-resolution 3D imaging, we identify phenotypes at multiple time points for previously uncharacterized genes and additional phenotypes for genes with previously reported mutant phenotypes. Unexpectedly, our analysis reveals that incomplete penetrance and variable expressivity are common even on a defined genetic background. In addition, we show that human disease genes are enriched for essential genes, thus providing a dataset that facilitates the prioritization and validation of mutations identified in clinical sequencing efforts. Identification and characterization, using a comprehensive embryonic phenotyping pipeline, of 410 lethal alleles during the generation of the first 1,751 of 5,000 unique gene knockouts produced by the International Mouse Phenotyping Consortium. Embryonic phenotypes and lethal genes Stephen Murray and colleagues, including those from the International Mouse Phenotyping Consortium, report on the first phase of the project to generate and phenotypically characterize 5,000 knockout mouse lines, the first systematic efforts to characterize the phenotypes of embryonic lethal mutations. They identify 410 lethal genes during the production of the first 1,751 unique gene knockouts, and characterize these in a comprehensive phenotyping pipeline that includes high-resolution 3D imaging methods. Unexpectedly, given the defined genetic background, they find a number of phenotypes with incomplete penetrance, including some gene knockouts with subviability. The authors also show that orthologues of these mouse essential genes are enriched in genes associated with human disease and show evidence of purifying selection in the human population.

Background: Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB integrity after PNI may lead to a better understanding of the mechanisms that contribute to chronic pain. Results: Here we used in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to establish a timecourse for BSCB permeability following PNI, produced by performing a spared nerve injury (SNI). From this longitudinal study, we found that the SNI group had a significant increase in BSCB permeability over time throughout the entire spinal cord. The BSCB opening had a delayed onset and the increase in permeability was transient, returning to control levels just over one day after the surgery. We also examined inter-strain differences in BSCB permeability using five mouse strains (B10, C57BL/6J, CD-1, A/J and BALB/c) that spanned the range of pain hypersensitivity. We found a significant increase in BSCB permeability in the SNI group that was dependent on strain but that did not correlate with the reported strain differences in PNI-induced tactile hypersensitivity. These results were consistent with a previous experiment using Evans Blue dye to independently assess the status of the BSCB permeability. Conclusions: DCE-MRI provides a sensitive and non-invasive method to follow BSCB permeability in the same group of mice over time. Examining differences between mouse strains, we demonstrated that there is an important genetically-based control of the PNI-induced increase in BSCB permeability and that the critical genetic determinants of BSCB opening after PNI are distinct from those that determine genetic variability in PNI-induced pain hypersensitivity.

Electron transport chains (ETCs) are ubiquitous in nearly all living systems. Replicating the complexity and control inherent in these multicomponent systems using ensembles of small molecules opens up promising avenues for molecular therapeutics, catalyst design, and the development of innovative energy conversion and storage systems. Here, we present a noncovalent, multistep artificial electron transport chains comprising cyclo[8]­pyrrole (1), a meso-aryl hexaphyrin(1.0.1.0.1.0) (naphthorosarin 2), and the small molecules I2 and trifluoroacetic acid (TFA). Specifically, we show that 1) electron transfer occurs from 1 to give I3 – upon the addition of I2, 2) proton-coupled electron transfer (PCET) from 1 to give H 3 2 •2+ and H 3 2 + upon the addition of TFA to a dichloromethane mixture of 1 and 2, and 3) that further, stepwise treatment of 1 and 2 with I2 and TFA promotes electron transport from 1 to give first I3 – and then H 3 2 •2+ and H 3 2 + . The present findings are substantiated through UV-vis-NIR, 1H NMR, electron paramagnetic resonance (EPR) spectroscopic analyses, cyclic voltammetry studies, and DFT calculations. Single-crystal structure analyses were used to characterize compounds in varying redox states.

Nature 537, 508–514 (2016); doi:10.1038/nature19356 In this Article, the author Wolfgang Wurst was erroneously omitted from the author list. They are associated with the affiliations: HelmholtzZentrum Munich, Institute of Developmental Genetics, 85764 Munich-Neuherberg, Germany; Technical Universityof Munich, Chair of Developmental Genetics, 85764 Munich-Neuherberg, Germany; German Center for Neurodegenerative Diseases (DZNE) Site Munich, 81377 Munich, Germany; and Munich Cluster for Systems Neurology (SyNergy), 81377 Munich, Germany.