Genome-wide patterns of nucleotide polymorphism in domesticated rice

Domesticated Asian rice (Oryza sativa) is one of the oldest domesticated crop species in the world, having fed more people than any other plant in human history. We report the patterns of DNA sequence variation in rice and its wild ancestor, O. rufipogon, across 111 randomly chosen gene fragments, and use these to infer the evolutionary dynamics that led to the origins of rice. There is a genome-wide excess of high-frequency derived single nucleotide polymorphisms (SNPs) in O. sativa varieties, a pattern that has not been reported for other crop species. We developed several alternative models to explain contemporary patterns of polymorphisms in rice, including a (i) selectively neutral population bottleneck model, (ii) bottleneck plus migration model, (iii) multiple selective sweeps model, and (iv) bottleneck plus selective sweeps model. We find that a simple bottleneck model, which has been the dominant demographic model for domesticated species, cannot explain the derived nucleotide polymorphism site frequency spectrum in rice. Instead, a bottleneck model that incorporates selective sweeps, or a more complex demographic model that includes subdivision and gene flow, are more plausible explanations for patterns of variation in domesticated rice varieties. If selective sweeps are indeed the explanation for the observed nucleotide data of domesticated rice, it suggests that strong selection can leave its imprint on genome-wide polymorphism patterns, contrary to expectations that selection results only in a local signature of variation.     

Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure

Micro RNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. They play a crucial role in the regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response. Although miRNA levels are substantially altered in tumors, their role in carcinogenesis, specifically at the early pre-cancerous stages, has not been established. Here we report that exposure of Fisher 344 rats to tamoxifen, a potent hepatocarcinogen in rats, for 24 weeks leads to substantial changes in the expression of miRNA genes in the liver. We noted a significant up-regulation of known oncogenic miRNAs, such as the 17-92 cluster, miR-106a, and miR-34. Furthermore, we confirmed the corresponding changes in the expression of proteins targeted by these miRNAs, which include important cell cycle regulators, chromatin modifiers, and expression regulators implicated in carcinogenesis. All these miRNA changes correspond to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Thus, our findings indicate that miRNA changes occur prior to tumor formation and are not merely a consequence of a transformed state.     

Association between frailty and 30-day outcomes after discharge from hospital

Background:Readmissions after hospital discharge are common and costly, but prediction models are poor at identifying patients at high risk of readmission. We evaluated the impact of frailty on readmission or death within 30 days after discharge from general internal medicine wards.Methods:We prospectively enrolled patients discharged from 7 medical wards at 2 teaching hospitals in Edmonton. Frailty was defined by means of the previously validated Clinical Frailty Scale. The primary outcome was the composite of readmission or death within 30 days after discharge.Results:Of the 495 patients included in the study, 162 (33%) met the definition of frailty: 91 (18%) had mild, 60 (12%) had moderate, and 11 (2%) had severe frailty. Frail patients were older, had more comorbidities, lower quality of life, and higher LACE scores at discharge than those who were not frail. The composite of 30-day readmission or death was higher among frail than among nonfrail patients (39 [24.1%] v. 46 [13.8%]). Although frailty added additional prognostic information to predictive models that included age, sex and LACE score, only moderate to severe frailty (31.0% event rate) was an independent risk factor for readmission or death (adjusted odds ratio 2.19, 95% confidence interval 1.12–4.24).Interpretation:Frailty was common and associated with a substantially increased risk of early readmission or death after discharge from medical wards. The Clinical Frailty Scale could be useful in identifying high-risk patients being discharged from general internal medicine wards.Readmissions within 30 days after hospital discharge are common and costly occurrences. Although many studies have attempted to identify patients at highest risk of readmission, neither experienced clinicians nor experienced researchers using rigorously developed administrative data-rich algorithms can accurately predict which patients will not successfully transition back into the community.^1–6 This suggests that currently unrecognized factors likely play a major role in readmission risk. Identification of these factors would be important for future initiatives to reduce readmission rates by targeting resources to those at highest risk.Frailty is a frequently underdiagnosed condition, with prevalence estimates ranging from 27% to 80% among inpatients^7–9 and from 4% to 59% among older adults living in the community,¹⁰ depending on the frailty measure used and the population evaluated. Frailty is a multidimensional syndrome of decreased reserve and resistance to stressors leading to increased vulnerability to adverse outcomes.^11–14 The 2 models of frailty most commonly used in the literature are the phenotype model (e.g., the approach proposed by Fried and colleagues,¹⁵ which is based on 5 objective variables assessed at one point in time that do not include psychosocial and cognitive variables) and the cumulative deficit model (e.g., the Clinical Frailty Index, which is based on a mix of more than 30 variables capturing function in many domains over time).^16–18Although the gold standard for frailty assessment is a comprehensive geriatric assessment by a multidisciplinary team, both the phenotype and cumulative deficit models appear reasonably accurate for identifying frailty. However, both are somewhat cumbersome for routine use at the bedside.¹² For these reasons, the Clinical Frailty Scale was developed and relies on clinical judgment based on history taking and clinical examination. The Clinical Frailty Scale is easy to administer at the bedside; has been used by physicians, allied health professionals and research assistants; does not require any special equipment; is highly correlated with the Fried frailty index (r = 0.8);¹⁷ and appears to be valid, reliable and reproducible.¹⁹ Some risk-prediction models, such as the LACE Index, have tried to incorporate frailty, but they did not find it to be a significant independent variable, possibly owing to the frailty measure used. A systematic review of 30 risk-prediction models for hospital readmission found that only 2 included functional status.⁴We conducted a study to evaluate whether frailty identified using the Clinical Frailty Scale is an independent predictor of death or readmission within 30 days after discharge from hospital.     

Demographically-Based Evaluation of Genomic Regions under Selection in Domestic Dogs

Controlling for background demographic effects is important for accurately identifying loci that have recently undergone positive selection. To date, the effects of demography have not yet been explicitly considered when identifying loci under selection during dog domestication. To investigate positive selection on the dog lineage early in the domestication, we examined patterns of polymorphism in six canid genomes that were previously used to infer a demographic model of dog domestication. Using an inferred demographic model, we computed false discovery rates (FDR) and identified 349 outlier regions consistent with positive selection at a low FDR. The signals in the top 100 regions were frequently centered on candidate genes related to brain function and behavior, including LHFPL3, CADM2, GRIK3, SH3GL2, MBP, PDE7B, NTAN1, and GLRA1. These regions contained significant enrichments in behavioral ontology categories. The 3^rd top hit, CCRN4L, plays a major role in lipid metabolism, that is supported by additional metabolism related candidates revealed in our scan, including SCP2D1 and PDXC1. Comparing our method to an empirical outlier approach that does not directly account for demography, we found only modest overlaps between the two methods, with 60% of empirical outliers having no overlap with our demography-based outlier detection approach. Demography-aware approaches have lower-rates of false discovery. Our top candidates for selection, in addition to expanding the set of neurobehavioral candidate genes, include genes related to lipid metabolism, suggesting a dietary target of selection that was important during the period when proto-dogs hunted and fed alongside hunter-gatherers.     

Distribution and Some Traits of Biology of Sculpins of Genus Triglops (Cottidae) in the Sea of Japan

Journal of Ichthyology - It was revealed that the southern border of the range of spectacled sculpin Triglops scepticus runs in the region of 37°23′ N. It has been confirmed that the...     

Structural basis of diversity and homodimerization specificity of zinc-finger-associated domains in Drosophila

In arthropods, zinc finger-associated domains (ZADs) are found at the N-termini of many DNA-binding proteins with tandem arrays of Cys2-His2 zinc fingers (ZAD-C2H2 proteins). ZAD-C2H2 proteins undergo fast evolutionary lineage-specific expansion and functional diversification. Here, we show that all ZADs from Drosophila melanogaster form homodimers, but only certain ZADs with high homology can also heterodimerize. CG2712, for example, is unable to heterodimerize with its paralog, the previously characterized insulator protein Zw5, with which it shares 46% homology. We obtained a crystal structure of CG2712 protein''s ZAD domain that, in spite of a low sequence homology, has similar spatial organization with the only known ZAD structure (from Grauzone protein). Steric clashes prevented the formation of heterodimers between Grauzone and CG2712 ZADs. Using detailed structural analysis, site-directed mutagenesis, and molecular dynamics simulations, we demonstrated that rapid evolutionary acquisition of interaction specificity was mediated by the more energy-favorable formation of homodimers in comparison to heterodimers, and that this specificity was achieved by multiple amino acid substitutions resulting in the formation or breaking of stabilizing interactions. We speculate that specific homodimerization of ZAD-C2H2 proteins is important for their architectural role in genome organization.     

A 28S rDNA-based phylogeny of the nematode family Acuariidae (Spirurida) parasitic in vertebrates

The aim of this study was to investigate the phylogenetic relationships of nematodes of the family Acuariidae using partial large subunit nuclear ribosomal DNA (28S) sequences of 15 genera represented by 18 species. The results confirmed the monophyly of the family Acuariidae and supported its close relationship with nematodes of the family Cystidicolidae. Two major clades were revealed within Acuariidae, one represented by nematodes of the subfamily Schistorophinae and another composed of members of the subfamilies Acuariinae and Seuratiinae. The collarette was shown to be a structure that arose several times within the clade Acuariinae–Seuratiinae. As a result, we suggest the suppression of the subfamily Seuratiinae and inclusion of its genera within the subfamily Acuariinae. Morphological characters, host ranges and life cycles of the taxa included in the analyses are discussed as well as the possible relationships of remaining acuariid genera within the revealed subclades. Additionally, we propose an amended generic diagnosis of Syncuaria Gilbert, 1927 to accommodate Syncuaria sagittata (Rudolphi, 1809) n. comb. and Syncuaria longevaginata (Molin, 1860) Skrjabin, Sobolev, & Ivashkin, 1965. New host and geographic records are also presented.