Exploring the elephant: histopathology in high-throughput phenotyping of mutant mice

Recent advances in gene knockout techniques and the in vivo analysis of mutant mice, together with the advent of large-scale projects for systematic mouse mutagenesis and genome-wide phenotyping, have allowed the creation of platforms for the most complete and systematic analysis of gene function ever undertaken in a vertebrate. The development of high-throughput phenotyping pipelines for these and other large-scale projects allows investigators to search and integrate large amounts of directly comparable phenotype data from many mutants, on a genomic scale, to help develop and test new hypotheses about the origins of disease and the normal functions of genes in the organism. Histopathology has a venerable history in the understanding of the pathobiology of human and animal disease, and presents complementary advantages and challenges to in vivo phenotyping. In this review, we present evidence for the unique contribution that histopathology can make to a large-scale phenotyping effort, using examples from past and current programmes at Lexicon Pharmaceuticals and The Jackson Laboratory, and critically assess the role of histopathology analysis in high-throughput phenotyping pipelines

Effect of Tempering on the Bainitic Microstructure Evolution Correlated with the Hardness in a Low-Alloy Medium-Carbon Steel

A low-alloy medium-carbon bainitic steel was isothermally tempered at 300 degrees C for up to 24 hours which led to a significant hardness decrease. In order to explain the decreasing hardness, extensive microstructural characterization using scanning and transmission electron microscopy, X-ray diffraction, and atom probe tomography was conducted. The experimental work was further supplemented by thermodynamic and kinetic simulations. It is found that the main underlying reason for the hardness reduction during tempering is related to dislocation annihilation, possibly also with corresponding changes in Cottrell atmospheres. On the other hand, cementite precipitate size, effective grain size of the bainite, and retained austenite fraction appear unchanged over the whole tempering cycle

Verbal behavior

Many children with autism cannot effectively ask wh-questions to mand for information, even though they may have extensive tact, intraverbal, and receptive language skills. Whquestions are typically mands because they occur under the control of establishing operations (EOs) and result in specific reinforcement. The current study first investigated a procedure to teach the mand ''where?'' to children with autism by contriving an EO for the location of a missing item. Following the successful acquisition of this mand, an establishing operation for a specific person was contrived to teach the mand ''who?'' The results showed that the children acquired these mands when the relevant establishing operations were manipulated as independent variables. The children also demonstrated generalization to untrained items and to the natural environment. These results have implications for methods of language instruction for children who have difficulty acquiring mands for information

Rapport för 2018 års kusttrålningsundersökning av kustnära fiskbestånd längs den svenska västkusten

Kusttrålningar har genomförts längs svenska kusten i Västerhavet sedan 2001. En huvudsaklig målsättning sedan starten har varit att övervaka utvecklingen av lokala bestånd och kustkomponenter av bestånd för ett urval av fiskarter med särskild fokus på torsk. Sedan 2009 är provtagningen fokuserad till kustavsnittet med skärgård mellan Fladen banken i söder och Singlefjorden i norr och sedan 2013 är provtagningen anpassad för att även övervaka fisksamhällets utveckling för Havsmiljödirektivet vad det gäller biologisk mångfald och marina näringsvävar. Årets kusttrålning genomfördes den 3-13 september 2018 då sammanlagt 32 trålstationer besöktes i norra Västerhavet. I kustområden gjordes 24 tråldrag och i utsjön gjordes åtta tråldrag. Fångsterna av torsk längs kusten under 2018 låg i stort sätt på samma låga nivå som föregående år. Förekomsten av stor könsmogen torsk längs kusten var fortsatt mycket låg; den största torsken som fångades i kustområdena under 2018 var 56 cm lång och fångades i Askeröfjorden. Fångsterna av torsk i utsjön under 2018 indikerar i jämförelse med 2017 års provtagning en fortsatt minskning. Fångsterna av torsk i utsjön 2018 var de lägsta som registrerats sedan provtagningen började. Vitling är en av de vanligaste fiskarterna som fångas i kusttrålningen under de senaste åren (2013-2018). De negativa trenderna för vitling både i utsjön och i kustområdena fortsatte under 2018 på samma sätt som under 2017. Fångstnivåerna för kolja i kustområdena var på en liknande nivå som under 2017 års kusttrålning samtidigt som koljan i utsjön befann sig på den lägsta nivå som registrerats sedan kusttrålningen startade. Generellt, vad det gäller torskfiskar så utgjordes fångsterna nästan uteslutande av juvenil fisk. Två arter av rocka fångades – knaggrocka och klorocka. Totalt fångades 48 olika fiskarter

ADAM12 induces actin cytoskeleton and extracellular matrix reorganization during early adipocyte differentiation by regulating beta1 integrin function

Changes in cell shape are a morphological hallmark of differentiation. In this study we report that the expression of ADAM12, a disintegrin and metalloprotease, dramatically affects cell morphology in preadipocytes, changing them from a flattened, fibroblastic appearance to a more rounded shape. We showed that the highest levels of ADAM12 mRNA were detected in preadipocytes at the critical stage when preadipocytes become permissive for adipogenic differentiation. Furthermore, as assessed by immunostaining, ADAM12 was transiently expressed at the cell surface concomitant with the reduced activity of beta1 integrin. Co-immunoprecipitation studies indicated the formation of ADAM12/beta1 integrin complexes in these preadipocytes. Overexpression of ADAM12 at the cell surface of 3T3-L1 preadipocytes achieved by transient transfection or retroviral transduction led to the disappearance of the extensive network of actin stress fibers that are characteristic of these cells, and its reorganization into a cortical network located beneath the cell membrane. The cells became more rounded, exhibited fewer vinculin-positive focal adhesions, and adhered less efficiently to fibronectin in attachment assays. Moreover, ADAM12-expressing cells were more prone to apoptosis, which could be prevented by treating the cells with beta1-activating antibodies. A reduced and re-organized fibronectin-rich extracellular matrix accompanied these changes. In addition, beta1 integrin was more readily extracted with Triton X-100 from cells overexpressing ADAM12 than from control cells. Collectively, these results show that surface expression of ADAM12 impairs the function of beta1 integrins and, consequently, alters the organization of the actin cytoskeleton and extracellular matrix. These events may be necessary for early adipocyte differentiation