Apoptotic cell clearance components in inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease of the synovial joints that affects ~1% of the human population. Joint swelling and bone erosion, hallmarks of RA, contribute to disability and, sometimes, loss of life. Mechanistically, disease is driven by immune dysregulation characterized by circulating autoantibodies, inflammatory mediators, tissue degradative enzymes, and metabolic dysfunction of resident stromal and recruited immune cells. Cell death by apoptosis has been therapeutically explored in animal models of RA due to the comparisons drawn between synovial hyperplasia and paucity of apoptosis in RA with the malignant transformation of cancer cells. Several efforts to induce cell death have shown benefits in reducing the development and/or severity of the disease. Apoptotic cells are cleared by phagocytes in a process known as efferocytosis, which differs from microbial phagocytosis in its "immuno-silent," or anti-inflammatory, nature. Failures in efferocytosis have been linked to autoimmune disease, whereas administration of apoptotic cells in RA models effectively inhibits inflammatory indices, likely though efferocytosis-mediated resolution-promoting mechanisms. However, the nature of signaling pathways elicited and the molecular identity of clearance mediators in RA are understudied. Furthermore, canonical efferocytosis machinery elements also play important non-canonical functions in homeostasis and pathology. Here, we discuss the roles of efferocytosis machinery components in models of RA and discuss their potential involvement in disease pathophysiology.

PLANTdataHUB: a collaborative platform for continuous FAIR data sharing in plant research.

In modern reproducible, hypothesis-driven plant research, scientists are increasingly relying on research data management (RDM) services and infrastructures to streamline the processes of collecting, processing, sharing, and archiving research data. FAIR (i.e., findable, accessible, interoperable, and reusable) research data play a pivotal role in enabling the integration of interdisciplinary knowledge and facilitating the comparison and synthesis of a wide range of analytical findings. The PLANTdataHUB offers a solution that realizes RDM of scientific (meta)data as evolving collections of files in a directory - yielding FAIR digital objects called ARCs - with tools that enable scientists to plan, communicate, collaborate, publish, and reuse data on the same platform while gaining continuous quality control insights. The centralized platform is scalable from personal use to global communities and provides advanced federation capabilities for institutions that prefer to host their own satellite instances. This approach borrows many concepts from software development and adapts them to fit the challenges of the field of modern plant science undergoing digital transformation. The PLANTdataHUB supports researchers in each stage of a scientific project with adaptable continuous quality control insights, from the early planning phase to data publication. The central live instance of PLANTdataHUB is accessible at (https://git.nfdi4plants.org), and it will continue to evolve as a community-driven and dynamic resource that serves the needs of contemporary plant science.

Longitudinal strain correlates with 6-minute walk distance whereas ejection fraction and diastolic parameters do not.

BACKGROUND: Impaired functional capacity is a common symptom in patients with heart failure. Standard measures of left ventricular (LV) function, such as ejection fraction (EF) and LV diastolic parameters, do not correlate with measures of functional capacity. The aim of this study is to determine if measures of global and regional LV strain better correlate with 6-minute walk distance than does EF or measures of LV diastolic function. METHODS: 120 patients referred to a cardiology clinic for evaluation of known or suspected heart failure were approached for enrollment. Of those 120 patients, 58 had an echocardiogram within 3 months of enrollment with images adequate for regional and global strain assessment, had no contra-indication to exercise testing, and had no previously documented non-cardiac explanation for dyspnea on exertion. In those 58 patients, 6-minute walk distance was measured, LV EF was determined with Simpson's biplane method, and global and regional longitudinal strain were measured with TomTec Image Arena 4.5.1 software. RESULTS: LV EF had no correlation with 6-minute walk distance (r = 0.22, p = 0.09) even when controlling for age, gender, and BMI (p = 0.07). No measures of LV diastolic function (including E velocity, Deceleration Time, e' annular velocities, or E/e') had a correlation with 6-minute walk distance. Multiple measures of global and regional LV longitudinal systolic function had a correlation with 6-minute walk distance. Longitudinal strain of the basal LV segments had the strongest correlation with 6-minute walk distance (r= -0.36, p = 0.005), and correlation persisted after controlling for age, gender, BMI, and systolic blood pressure (p = 0.004). CONCLUSIONS: Longitudinal strain correlates with a measure of functional capacity, but LVEF and traditional measures of LV diastolic dysfunction do not. Measures of longitudinal strain, especially in basal LV segments, will likely be an important marker of clinically relevant LV function.

Genomic basis of fishing-associated selection varies with population density.

Fisheries induce one of the strongest anthropogenic selective pressures on natural populations, but the genetic effects of fishing remain unclear. Crucially, we lack knowledge of how capture-associated selection and its interaction with reductions in population density caused by fishing can potentially shift which genes are under selection. Using experimental fish reared at two densities and repeatedly harvested by simulated trawling, we show consistent phenotypic selection on growth, metabolism, and social behavior regardless of density. However, the specific genes under selection-mainly related to brain function and neurogenesis-varied with the population density. This interaction between direct fishing selection and density could fundamentally alter the genomic responses to harvest. The evolutionary consequences of fishing are therefore likely context dependent, possibly varying as exploited populations decline. These results highlight the need to consider environmental factors when predicting effects of human-induced selection and evolution.

Environmental correlates of adaptive diversification in postglacial freshwater fishes.

Determining how environmental conditions contribute to divergence among populations and drive speciation is fundamental to resolving mechanisms and understanding outcomes in evolutionary biology. Postglacial freshwater fish species in the Northern Hemisphere are ideal biological systems to explore the effects of environment on diversification in morphology, ecology, and genetics (ecomorph divergences) within lakes. To date, various environmental factors have been implicated in the presence of multiple ecomorphs within particular lakes or regions. However, concerted evidence for generalizable patterns in environmental variables associated with speciation across geographical regions and across species and genera has been lacking. Here, we aimed to identify key biotic and abiotic factors associated with ecological divergence of postglacial freshwater fish species into multiple sympatric ecomorphs, focusing on species in the well-studied, widespread, and co-distributed genera Gasterosteus, Salvelinus, and Coregonus (stickleback, charr, and whitefish, respectively). We found that the presence of multiple sympatric ecomorphs tended to be associated with increasing lake surface area, maximum depth, and nutrient availability. In addition, predation, competition, and prey availability were suggested to play a role in divergence into multiple ecomorphs, but the effects of biotic factors require further study. Although we identified several environmental factors correlated with the presence of multiple ecomorphs, there were substantial data gaps across species and regions. An improved understanding of these systems may provide insight into both generalizable environmental factors involved in speciation in other systems, and potential ecological and evolutionary responses of species complexes when these variables are altered by environmental change.

Improved maize reference genome with single-molecule technologies.

Complete and accurate reference genomes and annotations provide fundamental tools for characterization of genetic and functional variation. These resources facilitate the determination of biological processes and support translation of research findings into improved and sustainable agricultural technologies. Many reference genomes for crop plants have been generated over the past decade, but these genomes are often fragmented and missing complex repeat regions. Here we report the assembly and annotation of a reference genome of maize, a genetic and agricultural model species, using single-molecule real-time sequencing and high-resolution optical mapping. Relative to the previous reference genome, our assembly features a 52-fold increase in contig length and notable improvements in the assembly of intergenic spaces and centromeres. Characterization of the repetitive portion of the genome revealed more than 130,000 intact transposable elements, allowing us to identify transposable element lineage expansions that are unique to maize. Gene annotations were updated using 111,000 full-length transcripts obtained by single-molecule real-time sequencing. In addition, comparative optical mapping of two other inbred maize lines revealed a prevalence of deletions in regions of low gene density and maize lineage-specific genes.

Anatomical study of the mastoid foramina and mastoid emissary veins: classification and application to localizing the sigmoid sinus.

The mastoid foramen (MF) is located on the mastoid process of the temporal bone, adjacent to the occipitomastoid suture or the parietomastoid suture, and contains the mastoid emissary vein (MEV). In retrosigmoid craniotomy, the MEV has been used to localize the position of the sigmoid sinus and, thus, the placement of the initial burr hole. Therefore, this study aimed to examine the exact location and variants of the MF and MEV to determine if their use in localizing the sigmoid sinus is reasonable. The sample in this study comprised 22 adult dried skulls (44 sides). MF were identified and classified into five types based on location, prevalence, whether they communicated with the sigmoid sinus and exact entrance into the groove of the sigmoid sinus. The diameters and relative locations of the MF in the skull were measured and recorded. Finally, the skulls were drilled to investigate the course of the MEV. Additionally, ten latex-injected sides from human cadavers were also dissected to follow the MEV, especially in cases with more than one vein. We found that type I MFs (single foramen) were the most prevalent (50%). These MFs were mainly located on the occipitomastoid suture; only one case on the right side was adjacent to the parietomastoid suture. Type II (paired foramina) was the second most prevalent (22.73%), followed by type III (13.64%), type 0 (9.09%), and type IV (4.55%). The diameter of the external opening in a connecting MF (2.43 ± 0.79) was twice that of a non-connecting MF (1.14 ± 0.56). Interestingly, on one side, two MFs on the external surface shared a single internal opening; the MEV bifurcated. MFs followed three different courses: ascending, almost horizontal, and descending. Regardless of how many external openings there were for the MF, these all ended at a single opening in the groove for the sigmoid sinus. For cadaveric specimens with multiple MEVs, all terminated in the sigmoid sinus as a single vein, with the more medial veins terminating more medially into the sinus. Based on our study, the MF/MEV can guide the surgeon and help localize the deeper-lying sigmoid sinus. Knowledge of this anatomical relationship could be an adjunct to neuronavigational technologies.

Impact of Xylella fastidiosa subspecies pauca in European olives.

Xylella fastidiosa is the causal agent of plant diseases that cause massive economic damage. In 2013, a strain of the bacterium was, for the first time, detected in the European territory (Italy), causing the Olive Quick Decline Syndrome. We simulate future spread of the disease based on climatic-suitability modeling and radial expansion of the invaded territory. An economic model is developed to compute impact based on discounted foregone profits and losses in investment. The model projects impact for Italy, Greece, and Spain, as these countries account for around 95% of the European olive oil production. Climatic suitability modeling indicates that, depending on the suitability threshold, 95.5 to 98.9%, 99.2 to 99.8%, and 84.6 to 99.1% of the national areas of production fall into suitable territory in Italy, Greece, and Spain, respectively. For Italy, across the considered rates of radial range expansion the potential economic impact over 50 y ranges from 1.9 billion to 5.2 billion Euros for the economic worst-case scenario, in which production ceases after orchards die off. If replanting with resistant varieties is feasible, the impact ranges from 0.6 billion to 1.6 billion Euros. Depending on whether replanting is feasible, between 0.5 billion and 1.3 billion Euros can be saved over the course of 50 y if disease spread is reduced from 5.18 to 1.1 km per year. The analysis stresses the necessity to strengthen the ongoing research on cultivar resistance traits and application of phytosanitary measures, including vector control and inoculum suppression, by removing host plants.

Effects of fluoroquinolones and tetracyclines on mitochondria of human retinal MIO-M1 cells.

Our goal was to explore the detrimental impacts of ciprofloxacin (CPFX) and tetracycline (TETRA) on human retinal Müller (MIO-M1) cells in vitro. Cells were exposed to 30, 60 and 120 µg/ml of CPFX and TETRA. The cellular metabolism was measured with the MTT assay. The JC-1 and CM-H2DCFDA assays were used to evaluate the levels of mitochondrial membrane potential (MMP) and ROS (reactive oxygen species), respectively. Mitochondrial DNA (mtDNA) copy number, along with gene expression levels associated with apoptotic (BAX, BCL2-L13, BCL2, CASP-3 and CASP-9), inflammatory (IL-6, IL-1ß, TGF-α, TGF-ß1 and TGF-ß2) and antioxidant pathways (SOD2, SOD3, GPX3 and NOX4) were analyzed via Quantitative Real-Time PCR (qRT-PCR). Bioenergetic profiles were measured using the Seahorse® XF Flux Analyzer. Cells exposed 24 h to 120 µg/ml TETRA demonstrated higher cellular metabolism compared to vehicle-treated cells. At each time points, (i) all TETRA concentrations reduced MMP levels and (ii) ROS levels were reduced by TETRA 120 µg/ml treatment. TETRA caused (i) higher expression of CASP-3, CASP-9, TGF-α, IL-1B, GPX3 and SOD3 but (ii) decreased levels of TGF-B2 and SOD2. ATP production and spare respiratory capacity declined with TETRA treatment. Cellular metabolism was reduced with CPFX 120 µg/ml in all cultures and 60 µg/ml after 72 h. The CPFX 120 µg/ml reduced MMP in all cultures and ROS levels (72 h). CPFX treatment (i) increased expression of CASP-3, CASP-9, and BCL2-L13, (ii) elevated the basal oxygen consumption rate, and (iii) lowered the mtDNA copy numbers and expression levels of TGF-B2, IL-6 and IL-1B compared to vehicle-control cells. We conclude that clinically relevant dosages of bactericidal and bacteriostatic antibiotics can have negative effects on the cellular metabolism and mitochondrial membrane potential of the retinal MIO-M1 cells in vitro. It is noteworthy to mention that apoptotic and inflammatory pathways in exposed cells were affected significantly This is the first study showing the negative impact of fluoroquinolones and tetracyclines on mitochondrial behavior of human retinal MIO-M1 cells.

iMLP, a predictor for internal matrix targeting-like sequences in mitochondrial proteins.

Matrix targeting sequences (MTSs) direct proteins from the cytosol into mitochondria. Efficient targeting often relies on internal matrix targeting-like sequences (iMTS-Ls) which share structural features with MTSs. Predicting iMTS-Ls was tedious and required multiple tools and webservices. We present iMLP, a deep learning approach for the prediction of iMTS-Ls in protein sequences. A recurrent neural network has been trained to predict iMTS-L propensity profiles for protein sequences of interest. The iMLP predictor considerably exceeds the speed of existing approaches. Expanding on our previous work on iMTS-L prediction, we now serve an intuitive iMLP webservice available at http://iMLP.bio.uni-kl.de and a stand-alone command line tool for power user in addition.

Differential effects of risuteganib and bevacizumab on AMD cybrid cells.

PURPOSE: Intravitreal injections of anti-vascular endothelial growth factor (VEGF) treatments are currently used to treat wet age-related macular degeneration (AMD), diabetic retinopathy, and macular edema. Chronic, repetitive treatments with anti-VEGF may have unintended consequences beyond the inhibition of angiogenesis. Most recently, clinical trials have been conducted with risuteganib (RSG, Luminate®), which is anti-angiogenic and has neuroprotective and anti-inflammatory properties. Mitochondrial damage and dysfunction play a major role in development of AMD. Transmitochondrial cybrids are cell lines established by fusing human retinal pigment epithelial (RPE) cells that are Rho0 (lacking mtDNA) with platelets isolated from AMD subjects or age-matched normal subjects. Cybrid cell lines have identical nuclei but mitochondria from different subjects, enabling investigation of the functional consequences of damaged AMD mitochondria. The present study compares the responses of AMD cybrids treated with bevacizumab (Bmab, Avastin®) versus risuteganib (RSG, Luminate®). METHODS: Cybrids were created by fusing mtDNA depleted ARPE-19 cells with platelets from AMD or age-matched normal patients. AMD (n = 5) and normal (n = 3) cybrids were treated for 48 h with or without 1x clinical dose of 1.25 mg/50 µl (25,000 µg/ml) of Bmab or 1.0 mg/50 µl (20,000 µg/ml) of RSG. Cultures were analyzed for levels of cleaved caspase 3/7 and NucLight Rapid Red staining (IncuCyte® Live Cell Imager), mitochondrial membrane potential (ΔΨm, JC1 assay) or reactive oxygen species (ROS, H2DCFDA assay). Expression levels of genes related to the following pathways were analyzed with qRT-PCR: Apoptosis (BAX, BCL2L13, CASP-3, -7, -9); angiogenesis (VEGFA, HIF1α, PDGF); integrins (ITGB-1, -3, -5, ITGA-3, -5, -V); mitochondrial biogenesis (PGC1α, POLG); oxidative stress (SOD2, GPX3, NOX4); inflammation (IL-6, -18, -1ß, IFN-ß1); and signaling (P3KCA, PI3KR1). Statistical analyses were performed using GraphPad Prism software. RESULTS: The untreated AMD cybrids had significantly higher levels of cleaved caspase 3/7 compared to the untreated normal cybrids. The Bmab-treated AMD cybrids showed elevated levels of cleaved caspase 3/7 compared to untreated AMD or RSG-treated AMD cybrids. The Bmab-treated cybrids had lower ΔΨm compared to untreated AMD or RSG-treated AMD cybrids. The ROS levels were not changed with Bmab or RSG treatment. Results showed that Bmab-treated cybrids had higher expression levels of inflammatory (IL-6, IL1-ß), oxidative stress (NOX4) and angiogenesis (VEGFA) genes compared to untreated AMD, while RSG-treated cybrids had lower expression levels of apoptosis (BAX), angiogenesis (VEGFA) and integrin (ITGB1) genes. CONCLUSIONS: These data suggest that the mechanism(s) of action of RSG, an integrin regulator, and Bmab, a recombinant monoclonal antibody, affect the AMD RPE cybrid cells differently, with the former having more anti-apoptosis properties, which may be desirable in treating degenerative ocular diseases.

The pitfalls and virtues of population genetic summary statistics: Detecting selective sweeps in recent divergences.

During evolution, genomes are shaped by a plethora of forces that can leave characteristic signatures. A common goal when studying diverging populations is to detect the signatures of selective sweeps, which can be rather difficult in complex demographic scenarios, such as under secondary contact. Moreover, the detection of selective sweeps, especially in whole-genome data, often relies heavily on a narrow set of summary statistics that are affected by a multitude of factors, frequently leading to false positives and false negatives. Simulating genomic regions makes it possible to control these demographic and population genetic factors. We used simulations of large genomic regions to determine how different secondary contact and sympatric speciation scenarios affect the footprint of hard and soft selective sweeps in the presence of varying degrees of gene flow and recombination. We explored the ability of an array of population genetic summary statistics to detect the footprints of these selective sweeps under specific demographies. We focussed on metrics that do not require phased data or ancestral sequences and therefore have wide applicability. We found that a newly developed beta diversity measure, B¯GD utperformed all other metrics in detecting selective sweeps and that FST also performed well. High accuracy was also found in Δπ and genotype distance-derived metrics. The performance of most metrics strongly depended on factors such as the presence of an allopatric phase, migration rates, recombination, population growth, and whether the sweep was hard or soft. We provide suggestions for locating and analysing the response to selective sweeps in whole-genome data.

Integrated Pedal System for Data Driven Rehabilitation.

We present a system capable of providing visual feedback for ergometer training, allowing detailed analysis and gamification. The presented solution can easily upgrade any existing ergometer device. The system consists of a set of pedals with embedded sensors, readout electronics and wireless communication modules and a tablet device for interaction with the users, which can be mounted on any ergometer, transforming it into a full analytical assessment tool with interactive training capabilities. The methods to capture the forces and moments applied to the pedal, as well as the pedal's angular position, were validated using reference sensors and high-speed video capture systems. The mean-absolute error (MAE) for load is found to be 18.82 N, 25.35 N, 0.153 Nm for Fx, Fz and Mx respectively and the MAE for the pedal angle is 13.2°. A fully gamified experience of ergometer training has been demonstrated with the presented system to enhance the rehabilitation experience with audio visual feedback, based on measured cycling parameters.

Cryptic species in White Cloud Mountain minnow, Tanichthys albonubes: Taxonomic and conservation implications.

Cryptic species describe two or more species that had mistakenly been considered to be a single species, a phenomenon that has been found throughout the tree of life. Recognizing cryptic species is key to estimating the real biodiversity of the world and understanding evolutionary processes. Molecular methods present an unprecedented opportunity for biologists to question whether morphologically similar populations are actually cryptic species. The minnow Tanichthys albonubes is a critically endangered freshwater fish and was classified as a second-class state-protected animal in China. Previous studies have revealed highly divergent lineages with similar morphological characters in this species. Herein, we tested for cryptic species across the ranges of all known wild populations of this minnow. Using multilocus molecular (one mitochondrial gene, two nuclear genes and 13 microsatellite loci) and morphological data for 230 individuals from eight populations, we found deep genetic divergence among these populations with subtle morphological disparity. Morphological examination found variance among these populations in the number of branched anal-fin rays. Based on genetic data, we inferred eight monophyletic groups that were well supported by haplotype network and population clustering analyses. Species delimitation methods suggested eight putative species in the T. albonubes complex. Molecular dating suggested that these cryptic species diverged in the period from the Pliocene to the Pleistocene. Based on these findings, we propose the existence of seven cryptic species in the T. albonubes complex. Our results highlight the need for a taxonomic revision of Tanichthys. What is more, the conservation status of and conservation strategies for the T. albonubes complex should be reassessed as soon as possible.

Native bighead carp Hypophthalmichthys nobilis and silver carp Hypophthalmichthys molitrix populations in the Pearl River are threatened by Yangtze River introductions as revealed by mitochondrial DNA.

Bighead carp Hypophthalmichthys nobilis and silver carp Hypophthalmichthys molitrix have been two economically important aquaculture species in China for centuries. In the past decades, bighead and silver carp have been introduced from the Yangtze River to many river systems in China, including the Pearl River, in annual, large-scale, stocking activities to enhance wild fisheries. Nonetheless, few studies have assessed the ecological or genetic impacts of such introductions on native conspecific fish populations. An mtDNA D-loop segment of 978 bp from 213 bighead carp samples from 9 populations and a 975 bp segment from 204 silver carp samples from 10 populations were obtained to evaluate genetic diversity and population integrity. Results from a haplotype network analysis revealed that most haplotypes of the Pearl River clustered with those of Yangtze River origin and only a small proportion were distinct, suggesting that both the native Pearl River bighead and silver carp populations are currently dominated by genetic material from the Yangtze River. The genetic diversity of Pearl River populations is high in both species because of this inter-population gene flow, but the diversity of native Pearl River populations is low. To preserve the native genetic diversity, stocking of non-native fingerlings should cease immediately and native Pearl River bighead and silver carp fish farms should be established. This research demonstrates the danger to native biodiversity across China because of the substantial, ongoing stock-enhancement activities without prior genetic assessment.

TMEA: A Thermodynamically Motivated Framework for Functional Characterization of Biological Responses to System Acclimation.

The objective of gene set enrichment analysis (GSEA) in modern biological studies is to identify functional profiles in huge sets of biomolecules generated by high-throughput measurements of genes, transcripts, metabolites, and proteins. GSEA is based on a two-stage process using classical statistical analysis to score the input data and subsequent testing for overrepresentation of the enrichment score within a given functional coherent set. However, enrichment scores computed by different methods are merely statistically motivated and often elusive to direct biological interpretation. Here, we propose a novel approach, called Thermodynamically Motivated Enrichment Analysis (TMEA), to account for the energy investment in biological relevant processes. Therefore, TMEA is based on surprisal analysis, which offers a thermodynamic-free energy-based representation of the biological steady state and of the biological change. The contribution of each biomolecule underlying the changes in free energy is used in a Monte Carlo resampling procedure resulting in a functional characterization directly coupled to the thermodynamic characterization of biological responses to system perturbations. To illustrate the utility of our method on real experimental data, we benchmark our approach on plant acclimation to high light and compare the performance of TMEA with the most frequently used method for GSEA.

Parallel selection on ecologically relevant gene functions in the transcriptomes of highly diversifying salmonids.

BACKGROUND: Salmonid fishes are characterised by a very high level of variation in trophic, ecological, physiological, and life history adaptations. Some salmonid taxa show exceptional potential for fast, within-lake diversification into morphologically and ecologically distinct variants, often in parallel; these are the lake-resident charr and whitefish (several species in the genera Salvelinus and Coregonus). To identify selection on genes and gene categories associated with such predictable diversifications, we analysed 2702 orthogroups (4.82 Mbp total; average 4.77 genes/orthogroup; average 1783 bp/orthogroup). We did so in two charr and two whitefish species and compared to five other salmonid lineages, which do not evolve in such ecologically predictable ways, and one non-salmonid outgroup. RESULTS: All selection analyses are based on Coregonus and Salvelinus compared to non-diversifying taxa. We found more orthogroups were affected by relaxed selection than intensified selection. Of those, 122 were under significant relaxed selection, with trends of an overrepresentation of serine family amino acid metabolism and transcriptional regulation, and significant enrichment of behaviour-associated gene functions. Seventy-eight orthogroups were under significant intensified selection and were enriched for signalling process and transcriptional regulation gene ontology terms and actin filament and lipid metabolism gene sets. Ninety-two orthogroups were under diversifying/positive selection. These were enriched for signal transduction, transmembrane transport, and pyruvate metabolism gene ontology terms and often contained genes involved in transcriptional regulation and development. Several orthogroups showed signs of multiple types of selection. For example, orthogroups under relaxed and diversifying selection contained genes such as ap1m2, involved in immunity and development, and slc6a8, playing an important role in muscle and brain creatine uptake. Orthogroups under intensified and diversifying selection were also found, such as genes syn3, with a role in neural processes, and ctsk, involved in bone remodelling. CONCLUSIONS: Our approach pinpointed relevant genomic targets by distinguishing among different kinds of selection. We found that relaxed, intensified, and diversifying selection affect orthogroups and gene functions of ecological relevance in salmonids. Because they were found consistently and robustly across charr and whitefish and not other salmonid lineages, we propose these genes have a potential role in the replicated ecological diversifications.

Inbreeding drives maize centromere evolution.

Functional centromeres, the chromosomal sites of spindle attachment during cell division, are marked epigenetically by the centromere-specific histone H3 variant cenH3 and typically contain long stretches of centromere-specific tandem DNA repeats (∼1.8 Mb in maize). In 23 inbreds of domesticated maize chosen to represent the genetic diversity of maize germplasm, partial or nearly complete loss of the tandem DNA repeat CentC precedes 57 independent cenH3 relocation events that result in neocentromere formation. Chromosomal regions with newly acquired cenH3 are colonized by the centromere-specific retrotransposon CR2 at a rate that would result in centromere-sized CR2 clusters in 20,000-95,000 y. Three lines of evidence indicate that CentC loss is linked to inbreeding, including (i) CEN10 of temperate lineages, presumed to have experienced a genetic bottleneck, contain less CentC than their tropical relatives; (ii) strong selection for centromere-linked genes in domesticated maize reduced diversity at seven of the ten maize centromeres to only one or two postdomestication haplotypes; and (iii) the centromere with the largest number of haplotypes in domesticated maize (CEN7) has the highest CentC levels in nearly all domesticated lines. Rare recombinations introduced one (CEN2) or more (CEN5) alternate CEN haplotypes while retaining a single haplotype at domestication loci linked to these centromeres. Taken together, this evidence strongly suggests that inbreeding, favored by postdomestication selection for centromere-linked genes affecting key domestication or agricultural traits, drives replacement of the tandem centromere repeats in maize and other crop plants. Similar forces may act during speciation in natural systems.

Sign-tracking is an expectancy-mediated behavior that relies on prediction error mechanisms.

When discrete localizable stimuli are used during appetitive Pavlovian conditioning, "sign-tracking" and "goal-tracking" responses emerge. Sign-tracking is observed when conditioned responding is directed toward the CS, whereas goal-tracking manifests as responding directed to the site of expected reward delivery. These behaviors seem to rely on distinct, though overlapping neural circuitries, and, possibly, distinct psychological processes as well, and are thought to be related to addiction vulnerability. One currently popular view is that sign-tracking reflects an incentive motivational process, whereas goal-tracking reflects the influence of more top-down cognitive processes. To test these ideas, we used illness-induced outcome-devaluation and Kamin blocking procedures to determine whether these behaviors rely on similar or distinct underlying associative mechanisms. In Experiments 1 and 2 we showed that outcome-devaluation reduced sign-tracking responses, demonstrating that sign-tracking is controlled by reward expectancies. We also observed that post-CS goal-tracking in these animals is also devaluation sensitive. To test whether these two types of behaviors rely on similar or different prediction error mechanisms, we next tested whether Kamin blocking effects could be observed across these two classes of behaviors. In Experiment 3 we asked if sign-tracking to a lever CS could block the development of goal-tracking to a tone CS; whereas in Experiment 4, we examined whether goal-tracking to a tone CS could block sign-tracking to a lever CS. In both experiments blocking effects were observed suggesting that both sign- and goal-tracking emerge via a common prediction error mechanism. Collectively, the studies reported here suggest that the psychological mechanisms mediating sign- and goal-tracking are more similar than is commonly acknowledged.

Performance of a prototype stationary catadioptric concentrating photovoltaic module.

A stationary catadioptric concentrating photovoltaic module with aperture area over 100 cm2, geometric concentration of 180×, and collection within 60° of polar incidence was designed, prototyped, and characterized. The module performance followed modeling closely with a peak power conversion efficiency of 26% for direct irradiance. Tracking of the sun is accomplished via translational micro-tracking completely internal to the module, avoiding the cost and complexity of mechanical two-axis trackers that point towards the sun. This demonstrates the potential for concentrating photovoltaic modules with significantly higher efficiency than industry standard silicon photovoltaic modules that could be installed in stationary configurations on rooftops.