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  1. Fulltext Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities
    Ikeda T, Ong EB, Watanabe N, Sakaguchi N, Maeda K, Koito A
    Sci Rep, 2016;6:19035.
    PMID: 26738439 DOI: 10.1038/srep19035
    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.
  2. Retention marker excretion suggests incomplete digesta mixing across the order primates
    Matsuda I, Espinosa-Gómez FC, Ortmann S, Sha JCM, Osman I, Nijboer J, et al.
    Physiol Behav, 2019 09 01;208:112558.
    PMID: 31125579 DOI: 10.1016/j.physbeh.2019.112558
    The digestive tract of animals, and the patterns how passage markers are excreted from them, have been fruitfully compared to chemical reactor models from engineering science. An important characteristic of idealized reactor models is the smoothness of the curves plotting marker concentrations in outflow (i.e., faeces) over time, which is the result of the assumed complete mixing of the marker with the reactor contents. Published excretion patterns from passage experiments in non-primate mammals appear to indicate a high degree of digesta mixing. In order to assess whether marker excretion graphs from primates differ from ideal outflow graphs, we performed passage experiments in eight individuals of three foregut-fermenting species (Pygathrix nemaeus, Trachypithecus auratus and Semnopithecus vetulus), and added them to available marker excretion curves from the literature. In the resulting collection, 23 out of a total of 25 patterns in foregut fermenters (21 individuals of 10 species from 7 studies), and 13 out of 15 in hindgut fermenters (9 individuals of 2 species from 2 studies), showed an irregular, 'spiky' pattern. We consider this proportion to be too high to be explained by experimental errors, and suggest that this may indicate a taxon-wide characteristic of particularly incomplete digesta mixing, acknowledging that further data from less related primate species are required for corroboration. Our hypothesis is in accordance with previous findings of a comparatively low degree of 'digesta washing' (differential retention of particulate and fluid digesta) in primates. Together with literature findings that suggest a low chewing efficiency in primates compared to other mammals, these observations indicate that in contrast to other herbivores, the success of the primate order is not derived from particularly elaborate adaptations of their ingestive and digestive physiology.
  3. Fulltext Chronic obstructive pulmonary disease and β-blocker treatment in Asian patients with heart failure
    Kubota Y, Tay WT, Asai K, Murai K, Nakajima I, Hagiwara N, et al.
    ESC Heart Fail, 2018 04;5(2):297-305.
    PMID: 29055972 DOI: 10.1002/ehf2.12228
    AIMS: Chronic obstructive pulmonary disease (COPD) and heart failure (HF) are increasingly frequent in Asia and commonly coexist in patients. However, the prevalence of COPD among Asian patients with HF and its impact on HF treatment are unclear.

    METHODS AND RESULTS: We compared clinical characteristics and treatment approaches between patients with or without a history of COPD, before and after 1:2 propensity matching (for age, sex, geographical region, income level, and ethnic group) in 5232 prospectively recruited patients with HF and reduced ejection fraction (HFrEF, <40%) from 11 Asian regions (Northeast Asia: South Korea, Japan, Taiwan, Hong Kong, and China; South Asia: India; Southeast Asia: Thailand, Malaysia, Philippines, Indonesia, and Singapore). Among the 5232 patients with HFrEF, a history of COPD was present in 8.3% (n = 434), with significant variation in geography (11.0% in Northeast Asia vs. 4.7% in South Asia), regional income level (9.7% in high income vs. 5.8% in low income), and ethnicity (17.0% in Filipinos vs. 5.2% in Indians) (all P 

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