Mortonkristoffersen1551

We successfully recovered up to 2945 loci with a mean of 1788 loci across the exome of specimens of varying age. Coverage was not significantly linked to specimen age, demonstrating the wide exploitability of museum specimens. We also recovered fragmentary mitogenomes compatible with Sanger-sequenced mtDNA. Our phylogenomic timetree revealed a Lower Cretaceous origin for crown group Carabinae, with the extinct Aplothorax nested within the genus Calosoma demonstrating the junior synonymy of Aplothorax syn. nov., resulting in the new combination Calosoma (Ctenosta) burchellii (Waterhouse, 1841) comb. nov. This study compellingly illustrates that HyRAD-X and phyloHyRAD efficiently provide genomic-level datasets informative at deep evolutionary scales.Quantification of inter-individual variability is a continuing challenge in risk assessment, particularly for compounds with complex metabolism and multi-organ toxicity. Toxicokinetic variability for perchloroethylene (perc) was previously characterized across three mouse strains and in one mouse strain with various degrees of liver steatosis. To further characterize the role of genetic variability in toxicokinetics of perc, we applied Bayesian population physiologically-based pharmacokinetic (PBPK) modeling to the data on perc and metabolites in blood/plasma and tissues of male mice from 45 inbred strains from the Collaborative Cross (CC) mouse population. After identifying the most influential PBPK parameters based on global sensitivity analysis, we fit the model with a hierarchical Bayesian population analysis using Markov chain Monte Carlo simulation. We found that the data from three commonly used strains were not representative of the full range of variability in perc and metabolite blood/plasma and tissue concentrations across the CC population. Using inter-strain variability as a surrogate for human inter-individual variability, we calculated dose-dependent, chemical-, and tissue-specific toxicokinetic variability factors (TKVFs) as candidate science-based replacements for the default uncertainty factor for human toxicokinetic variability of 100.5. We found that TKVFs for glutathione conjugation metabolites of perc showed the greatest variability, often exceeding the default, whereas those for oxidative metabolites and perc itself were generally less than the default. Overall, we demonstrate how a combination of a population-based mouse model such as the CC with Bayesian population PBPK modeling can reduce uncertainty in human toxicokinetic variability and increase accuracy and precision in quantitative risk assessment.The nucleotide composition, dinucleotide composition, and codon usage of many viruses differs from their hosts. These differences arise because viruses are subject to unique mutation and selection pressures that do not apply to host genomes; however, the molecular mechanisms that underlie these evolutionary forces are unclear. Here, we analysed the patterns of codon usage in 1,520 vertebrate-infecting viruses, focusing on parameters known to be under selection and associated with gene regulation. We find that GC content, dinucleotide content, and splicing and m6A modification-related sequence motifs are associated with the type of genetic material (DNA or RNA), strandedness, and replication compartment of viruses. In an experimental follow-up, we find that the effects of GC content on gene expression depend on whether the genetic material is delivered to the cell as DNA or mRNA, whether it is transcribed by endogenous or exogenous RNA polymerase, and whether transcription takes place in the nucleus or cytoplasm. Our results suggest that viral codon usage cannot be explained by a simple adaptation to the codon usage of the host - instead, it reflects the combination of multiple selective and mutational pressures, including the need for efficient transcription, export, and immune evasion.Color and color pattern are critical for animal camouflage, reproduction, and defense. Few studies, however, have attempted to identify candidate genes for color and color pattern in squamate reptiles, a colorful group with over 10,000 species. We used comparative transcriptomic analyses between white, orange, and yellow skin in a color-polymorphic species of anole lizard to 1) identify candidate color and color-pattern genes in squamates and 2) assess if squamates share an underlying genetic basis for color and color pattern variation with other vertebrates. Squamates have three types of chromatophores that determine color pattern guanine-filled iridophores, carotenoid- or pteridine-filled xanthophores/erythrophores, and melanin-filled melanophores. We identified 13 best candidate squamate color and color-pattern genes shared with other vertebrates six genes linked to pigment synthesis pathways, and seven genes linked to chromatophore development and maintenance. In comparisons of expression profiles between pigment-rich and white skin, pigment-rich skin upregulated the pteridine pathway as well as xanthophore/erythrophore development and maintenance genes; in comparisons between orange and yellow skin, orange skin upregulated the pteridine and carotenoid pathways as well as melanophore maintenance genes. Our results corroborate the predictions that squamates can produce similar colors using distinct color-reflecting molecules, and that both color and color-pattern genes are likely conserved across vertebrates. Furthermore, this study provides a concise list of candidate genes for future functional verification, representing a first step in determining the genetic basis of color and color pattern in anoles.LC3s are canonical proteins necessary for the formation of autophagosomes. We have previously established that two paralogs, LC3B and LC3C, have opposite activities in renal cancer, with LC3B playing an oncogenic role and LC3C a tumor-suppressing role. LC3C is an evolutionary late gene present only in higher primates and humans. Vacuolin-1 Its most distinct feature is a C-terminal 20-amino acid peptide cleaved in the process of glycine 126 lipidation. Here, we investigated mechanisms of LC3C-selective autophagy. LC3C autophagy requires noncanonical upstream regulatory complexes that include ULK3, UVRAG, RUBCN, PIK3C2A, and a member of ESCRT, TSG101. We established that postdivision midbody rings (PDMBs) implicated in cancer stem-cell regulation are direct targets of LC3C autophagy. LC3C C-terminal peptide is necessary and sufficient to mediate LC3C-dependent selective degradation of PDMBs. This work establishes a new noncanonical human-specific selective autophagic program relevant to cancer stem cells.Polarization of the actin cytoskeleton is vital for the collective migration of cells in vivo. During invasive border cell migration in Drosophila, actin polarization is directly controlled by the Hippo signaling complex, which resides at contacts between border cells in the cluster. Here, we identify, in a genetic screen for deubiquitinating enzymes involved in border cell migration, an essential role for nonstop/USP22 in the expression of Hippo pathway components expanded and merlin. Loss of nonstop function consequently leads to a redistribution of F-actin and the polarity determinant Crumbs, loss of polarized actin protrusions, and tumbling of the border cell cluster. Nonstop is a component of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional coactivator complex, but SAGA's histone acetyltransferase module, which does not bind to expanded or merlin, is dispensable for migration. Taken together, our results uncover novel roles for SAGA-independent nonstop/USP22 in collective cell migration, which may help guide studies in other systems where USP22 is necessary for cell motility and invasion.Dynamic targeting of the ULK1 complex to the ER is crucial for initiating autophagosome formation and for subsequent formation of ER-isolation membrane (IM; autophagosomal precursor) contact during IM expansion. Little is known about how the ULK1 complex, which comprises FIP200, ULK1, ATG13, and ATG101 and does not exist as a constitutively coassembled complex, is recruited and stabilized on the ER. Here, we demonstrate that the ER-localized transmembrane proteins Atlastin 2 and 3 (ATL2/3) contribute to recruitment and stabilization of ULK1 and ATG101 at the FIP200-ATG13-specified autophagosome formation sites on the ER. In ATL2/3 KO cells, formation of FIP200 and ATG13 puncta is unaffected, while targeting of ULK1 and ATG101 is severely impaired. Consequently, IM initiation is compromised and slowed. ATL2/3 directly interact with ULK1 and ATG13 and facilitate the ATG13-mediated recruitment/stabilization of ULK1 and ATG101. ATL2/3 also participate in forming ER-IM tethering complexes. Our study provides insights into the dynamic assembly of the ULK1 complex on the ER for autophagosome formation.Most cancer cells show chromosomal instability, a condition where chromosome missegregation occurs frequently. We found that chromosome oscillation, an iterative chromosome motion during metaphase, is attenuated in cancer cell lines. We also found that metaphase phosphorylation of Hec1 at serine 55, which is mainly dependent on Aurora A on the spindle, is reduced in cancer cell lines. The Aurora A-dependent Hec1-S55 phosphorylation level was regulated by the chromosome oscillation amplitude and vice versa Hec1-S55 and -S69 phosphorylation by Aurora A is required for efficient chromosome oscillation. Furthermore, enhancement of chromosome oscillation reduced the number of erroneous kinetochore-microtubule attachments and chromosome missegregation, whereas inhibition of Aurora A during metaphase increased such errors. We propose that Aurora A-mediated metaphase Hec1-S55 phosphorylation through chromosome oscillation, together with Hec1-S69 phosphorylation, ensures mitotic fidelity by eliminating erroneous kinetochore-microtubule attachments. Attenuated chromosome oscillation and the resulting reduced Hec1-S55 phosphorylation may be a cause of CIN in cancer cell lines.A set of recent neuroimaging studies observed that the perception of an illusory shape can elicit both positive and negative feedback modulations in different parts of the early visual cortex. When three Pac-Men shapes were aligned in such a way that they created an illusory triangle (i.e., the Kanizsa illusion), neural activity in early visual cortex was enhanced in those neurons that had receptive fields that overlapped with the illusory shape but suppressed in neurons whose receptive field overlapped with the Pac-Men inducers. These results were interpreted as congruent with the predictive coding framework, in which neurons in early visual cortex enhance or suppress their activity depending on whether the top-down predictions match the bottom-up sensory inputs. However, there are several plausible alternative explanations for the activity modulations. Here we tested a recent proposal (Moors, 2015) that the activity suppression in early visual cortex during illusory shape perception reflects neural adaptation to perceptually stable input. Namely, the inducers appear perceptually stable during the illusory shape condition (discs on which a triangle is superimposed), but not during the control condition (discs that change into Pac-Men). We examined this hypothesis by manipulating the perceptual stability of inducers. When the inducers could be perceptually interpreted as persistent circles, we replicated the up- and downregulation pattern shown in previous studies. However, when the inducers could not be perceived as persistent circles, we still observed enhanced activity in neurons representing the illusory shape but the suppression of activity in neurons representing the inducers was absent. Thus our results support the hypothesis that the activity suppression in neurons representing the inducers during the Kanizsa illusion is better explained by neural adaptation to perceptually stable input than by reduced prediction error.