Sequence-Based Mapping and Genome Editing Reveal Mutations in Stickleback Hps5 Cause Oculocutaneous Albinism and the casper Phenotype.

Here, we present and characterize the spontaneous X-linked recessive mutation casper, which causes oculocutaneous albinism in threespine sticklebacks (Gasterosteus aculeatus). In humans, Hermansky-Pudlak syndrome results in pigmentation defects due to disrupted formation of the melanin-containing lysosomal-related organelle (LRO), the melanosome. casper mutants display not only reduced pigmentation of melanosomes in melanophores, but also reductions in the iridescent silver color from iridophores, while the yellow pigmentation from xanthophores appears unaffected. We mapped casper using high-throughput sequencing of genomic DNA from bulked casper mutants to a region of the stickleback X chromosome (chromosome 19) near the stickleback ortholog of Hermansky-Pudlak syndrome 5 (Hps5). casper mutants have an insertion of a single nucleotide in the sixth exon of Hps5, predicted to generate an early frameshift. Genome editing using CRISPR/Cas9 induced lesions in Hps5 and phenocopied the casper mutation. Injecting single or paired Hps5 guide RNAs revealed higher incidences of genomic deletions from paired guide RNAs compared to single gRNAs. Stickleback Hps5 provides a genetic system where a hemizygous locus in XY males and a diploid locus in XX females can be used to generate an easily scored visible phenotype, facilitating quantitative studies of different genome editing approaches. Lastly, we show the ability to better visualize patterns of fluorescent transgenic reporters in Hps5 mutant fish. Thus, Hps5 mutations present an opportunity to study pigmented LROs in the emerging stickleback model system, as well as a tool to aid in assaying genome editing and visualizing enhancer activity in transgenic fish

SPG20 protein spartin is recruited to midbodies by ESCRT-III protein Ist1 and participates in cytokinesis.

Hereditary spastic paraplegias (HSPs, SPG1-46) are inherited neurological disorders characterized by lower extremity spastic weakness. Loss-of-function SPG20 gene mutations cause an autosomal recessive HSP known as Troyer syndrome. The SPG20 protein spartin localizes to lipid droplets and endosomes, and it interacts with tail interacting protein 47 (TIP47) as well as the ubiquitin E3 ligases atrophin-1-interacting protein (AIP)4 and AIP5. Spartin harbors a domain contained within microtubule-interacting and trafficking molecules (MIT) at its N-terminus, and most proteins with MIT domains interact with specific ESCRT-III proteins. Using yeast two-hybrid and in vitro surface plasmon resonance assays, we demonstrate that the spartin MIT domain binds with micromolar affinity to the endosomal sorting complex required for transport (ESCRT)-III protein increased sodium tolerance (Ist)1 but not to ESCRT-III proteins charged multivesicular body proteins 1-7. Spartin colocalizes with Ist1 at the midbody, and depletion of Ist1 in cells by small interfering RNA significantly decreases the number of cells where spartin is present at midbodies. Depletion of spartin does not affect Ist1 localization to midbodies but markedly impairs cytokinesis. A structure-based amino acid substitution in the spartin MIT domain (F24D) blocks the spartin-Ist1 interaction. Spartin F24D does not localize to the midbody and acts in a dominant-negative manner to impair cytokinesis. These data suggest that Ist1 interaction is important for spartin recruitment to the midbody and that spartin participates in cytokinesis

Taxes as Pandemic Controls

Tax policy can play important roles in limiting the spread of communicable disease and in managing the economic fallout of a pandemic. Taxes on business activities that bring workers or customers into close contact with each other offer efficient alternatives to broad regulatory measures, such as shutdowns, that have been effective but enormously costly. Corrective taxation also helps raise the revenue required to cover elevated government expenditure during a pandemic. Moreover, the restricted consumer choice that accompanies a pandemic reduces the welfare cost of raising tax revenue from higher-income taxpayers, making it a good time for deficit closure. Current U.S. tax measures serve some of these functions, but additional measures could further limit the spread of disease while also addressing government budget deficits

Revised Distribution Records of Some Minnesota Fishes

Recent collections of fishes from Minnesota have resulted in the addition of one species, Fundulus sciadicus (Cyprinodontidae), to the state\u27s inland faunal list. Additional information on the distribution of 12 other species (Notropis topeka, Notropis spilooterus, Ictiobus byprinellus, Carpiodes byprinus, Moxostoma valenciennesi, Notorus flavus, Morone chrysops, Lepomis megalotis, Stizostedion canadense, Percina shumardi, Etheostoma caeruleum, and Cottus bairdi) is presented. These new records are the result of field work in the Missouri River, Red River, and Lake Superior drainage systems of Minnesota

Proprioceptive perception of phase variability

Previous work has established that judgments of relative phase variability of 2 visually presented oscillators covary with mean relative phase. Ninety degrees is judged to be more variable than 0° or 180°, independently of the actual level of phase variability. Judged levels of variability also increase at 180°. This pattern of judgments matches the pattern of movement coordination results. Here, participants judged the phase variability of their own finger movements, which they generated by actively tracking a manipulandum moving at 0°, 90°, or 180°, and with 1 of 4 levels of Phase Variability. Judgments covaried as an inverted U-shaped function of mean relative phase. With an increase in frequency, 180° was judged more variable whereas 0° was not. Higher frequency also reduced discrimination of the levels of Phase Variability. This matching of the proprioceptive and visual results, and of both to movement results, supports the hypothesized role of online perception in the coupling of limb movements. Differences in the 2 cases are discussed as due primarily to the different sensitivities of the systems to the information

Issue-related learning in a gubernatorial campaign : a panel study.

This study is based on data from a three-wave telephone panel survey conducted during the 1998 governor\u27s race in Florida. The evidence suggests that a considerable amount of issue-related learning (having to do with candidate policy stands and group endorsements) took place over the course of the general election campaign, though substantial differences were observed from one issue area to the next. Further analysis indicates that learning was especially likely to occur among voters who (a) were more knowledgeable about political affairs to start with(confirming that the so-called knowledge gap may be exacerbated during campaigns); (b)scored high on a measure of advertising negativity (for one candidate, but not the other); and (c)early in the campaign, read their local newspaper less frequently. Consistent with prior research,TV news appears to have done little or nothing to boost issue-based learning among the electorate

Detection of Single Ion Spectra by Coulomb Crystal Heating

The coupled motion of ions in a radiofrequency trap has been used to connect the frequency- dependent laser-induced heating of a sympathetically cooled spectroscopy ion with changes in the fluorescence of a laser-cooled control ion. This technique, sympathetic heating spectroscopy, is demonstrated using two isotopes of calcium. In the experiment, a few scattered photons from the spectroscopy ion are transformed into a large deviation from the steady-state fluorescence of the control ion. This allows us to detect an optical transition where the number of scattered photons is below our fluorescence detection limit. Possible applications of the technique to molecular ion spectroscopy are briefly discussed.Comment: 7 Pages,10 Figure

Neurogenesis Deep Learning

Neural machine learning methods, such as deep neural networks (DNN), have achieved remarkable success in a number of complex data processing tasks. These methods have arguably had their strongest impact on tasks such as image and audio processing - data processing domains in which humans have long held clear advantages over conventional algorithms. In contrast to biological neural systems, which are capable of learning continuously, deep artificial networks have a limited ability for incorporating new information in an already trained network. As a result, methods for continuous learning are potentially highly impactful in enabling the application of deep networks to dynamic data sets. Here, inspired by the process of adult neurogenesis in the hippocampus, we explore the potential for adding new neurons to deep layers of artificial neural networks in order to facilitate their acquisition of novel information while preserving previously trained data representations. Our results on the MNIST handwritten digit dataset and the NIST SD 19 dataset, which includes lower and upper case letters and digits, demonstrate that neurogenesis is well suited for addressing the stability-plasticity dilemma that has long challenged adaptive machine learning algorithms.Comment: 8 pages, 8 figures, Accepted to 2017 International Joint Conference on Neural Networks (IJCNN 2017