Stable Display of Artificially Long Foreign Antigens on Chimeric Bamboo mosaic virus Particles

Plant viruses can be genetically modified to generate chimeric virus particles (CVPs) carrying heterologous peptides fused on the surface of coat protein (CP) subunits as vaccine candidates. However, some factors may be especially significant in determining the properties of chimeras. In this study, peptides from various sources and of various lengths were inserted into the Bamboo mosaic virus-based (BaMV) vector CP N-terminus to examine the chimeras infecting and accumulating in plants. Interestingly, it was found that the two different strains Foot-and-mouth disease virus (FMDV) VP1 antigens with flexible linker peptides (77 or 82 amino acids) were directly expressed on the BaMV CP, and the chimeric particles self-assembled and continued to express FMDV antigens. The chimeric CP, when directly fused with a large foreign protein (117 amino acids), can self-fold into incomplete virus particles or disks. The physicochemical properties of heterologus peptides N-terminus, complex strand structures of heterologus peptides C-terminus and different flexible linker peptides, can affect the chimera accumulation. Based on these findings, using plant virus-based chimeras to express foreign proteins can increase their length limitations, and engineered plant-made CVP-based vaccines have increasing potential for further development as novel vaccines.     

Relationship between uric acid and lipid accumulation product index by gender in Korean adults: The 2016 Korean National Health and Nutrition Examination Survey

AimsThe present study assesses the relationship between uric acid (UA) and lipid accumulation product index (LAP) by gender among Korean adults.MethodsData from 5670 subjects (2463 men and 3207 women) in the Korean National Health and Nutrition Examination Survey (KNHANES VII-1) 2016 were analyzed. LAP was divided into four quartiles (Q1–Q4).ResultsThere were several key findings. Compared with Q1, in the overall population, the odds ratios (ORs) of hyperuricemia (UA ≥ 7.0 mg/dL in men or UA ≥ 6.0 mg/dL in women) were significantly higher in Q2 [1.847 (95% confidence interval [CI], 1.325–2.575)], Q3 [3.050 (95% CI, 2.216–4.198)], and Q4 of LAP [6.367 (95% CI, 4.658–8.704)]. In men, the ORs of hyperuricemia were significantly higher in Q2 [1.658 (95% CI, 1.162–2.367)], Q3 [2.341 (95% CI, 1.656–3.308)], and Q4 [4.633 (95% CI, 3.290–6.525)] than Q1. In women, the ORs of hyperuricemia were significantly higher in Q2 [2.254 (95% CI, 1.085–4.680)], Q3 [5.402 (95% CI, 2.735–10.668)], and Q4 [11.025 (95% CI, 5.620–21.628)] than Q1. In addition, UA levels were positively associated with LAP level in men (r = 0.218; p < 0.001), women (r = 0.261; p < 0.001), and the overall population (r = 0.260; p < 0.001).ConclusionsHyperuricemia was positively associated with LAP in Korean men and women.     

Evaluation of the antidiarrhoeal effects of Zizyphus spina-christi stem bark in rats

The antidiarrhoeal effects of the methanol extract of Zizyphus spina-christi stem bark were evaluated in laboratory rodents. Studies on castor oil induced diarrhoea, intraluminal fluid accumulation, and gastrointestinal transit time were carried out. Results obtained revealed that the extract caused a dose dependent protection of rats against castor oil induced diarrhoea, decreased the intraluminal fluid accumulation and gastrointestinal transit. The intraperitoneal and oral LD(50) values were found to be 346+/-5.6 and 1200+/-41.2 mg/kg in mice. Preliminary phytochemical screening revealed the presence of glycosides, resins, saponins, and tannins. It is suggested that the extract may contain biologically active components that may be useful against diarrhoea, thereby justifying its use in ethnomedical practice as an antidiarrhoeal agent.     

Comparative evolutionary genetics of spontaneous mutations affecting fitness in rhabditid nematodes

Deleterious mutations are of fundamental importance to all aspects of organismal biology. Evolutionary geneticists have expended tremendous effort to estimate the genome-wide rate of mutation and the effects of new mutations on fitness, but the degree to which genomic mutational properties vary within and between taxa is largely unknown, particularly in multicellular organisms. Beginning with two highly inbred strains from each of three species in the nematode family Rhabditidae (Caenorhabditis briggsae, Caenorhabditis elegans, and Oscheius myriophila), we allowed mutations to accumulate in the relative absence of natural selection for 200 generations. We document significant variation in the rate of decay of fitness because of new mutations between strains and between species. Estimates of the per-generation mutational decay of fitness were very consistent within strains between assays 100 generations apart. Rate of mutational decay in fitness was positively associated with genomic mutation rate and negatively associated with average mutational effect. These results provide unambiguous experimental evidence for substantial variation in genome-wide properties of mutation both within and between species and reinforce conclusions from previous experiments that the cumulative effects on fitness of new mutations can differ markedly among related taxa.     

Mono-2-ethylhexyl phthalate induces the expression of genes involved in fatty acid synthesis in HepG2 cells

Mono-2-ethylhexyl phthalate (MEHP) is a major bioactive metabolite in the widely used industrial plasticizer diethylhexyl phthalate (DEHP) that has been found to be toxic to the liver. The aim of this study is to determine whether MEHP exposure can change the expression of fatty acid metabolism-related genes in HepG2 cells, which might be related to non-alcoholic fatty liver disease (NAFLD). The results revealed that exposure to MEHP promoted lipid accumulation in HepG2 cells. The levels of intracellular triglycerides in the hepatocytes increased after exposure to 0.8–100 μM MEHP for 24 h and 48 h. The genetic expressions of SREBP-1c, ChREBP, ACC1, FASN, and SCD significantly increased at 6 h after exposure to MEHP. At 24 h, the expression of the SREBP-1c and ChREBP genes remained increased, while the expression of the FASN and SCD genes decreased. At 48 h, the expression of SREBP-1c, ChREBP, ACC1, FASN, and SCD decreased. Furthermore, the levels of proteins including ACC1, FASN, SCD, and ChREBP (except SREBP-1c) increased at 24 h. These findings suggest that MEHP exposure can promote fatty acid synthesis in hepatocytes by regulating the expression of relevant genes and proteins, contributing to NAFLD.     

Clade extinction appears to balance species diversification in sister lineages of Afro-Oriental passerine birds

Recent analyses suggest that the number of species in a clade often increases rapidly at first, but that diversification subsequently slows, apparently as species fill ecological space. Support for diversity dependence comes largely from the failure of species richness to increase with clade age in some analyses of contemporary diversity. However, clades chosen for analysis generally are named taxa and thus are not selected at random. To avoid this potential bias, we analyzed the numbers of species and estimated ages of 150 pairs of sister clades established by dispersal of ancestral species between the Oriental and African biogeographic regions. The observed positive exponential relationship between clade size and age suggests that species diversify within clades without apparent limit. If this were true, the pattern of accumulation of sister-clade pairs with increasing age would be consistent with the random decline and extinction of entire clades, maintaining an overall balance in species richness. This “pulse” model of diversification is consistent with the fossil record of most groups and reconciles conflicting evidence concerning diversity dependence of clade growth.The close relationship between local species richness and characteristics of the physical environment supports the existence of ecological constraints on species coexistence mediated through competition and other interactions (1–3), although historical influences on diversity sometimes parallel gradients in the physical environment (4–6). If species richness were limited as ecological space filled, one would expect the net rate of species production to slow and the number of species in a clade to level off as species richness approached ecological constraints.Evidence for such “diversity-dependent diversification” consists mostly of (i) nonrandom concentrations of branch points (speciation events) toward the origin of a clade (7–12) and (ii) independence of the number of species and clade age in comparisons among clades (11–14). However, clades included in such analyses often are not randomly chosen. In particular, small clades may be ignored because they do not command interest, and large, older clades are often passed over because of incomplete sampling (15, 16). Moreover, most phylogenetic analyses of diversification include species in named higher taxa rather than clades that have diversified within particular regions.Further support for diversity limits comes from the fossil records of many higher taxa, which exhibit long-term stability in number of species (17–19). It is also clear that species and entire clades continually replace each other through time, and the dynamics of this process appear to include the decline and extinction of evolutionary groups as a component of the local and regional regulation of the number of coexisting species (20–25).We take advantage of the sister relationships of clades of passerine birds in two major biogeographic regions—tropical southern Asia [Oriental (OR)] and the continent of Africa [African (AF)]—to examine the independent diversification of sister clades of known stem ages, selected only because one of the ancestors had dispersed between the two continents at some time in the past. Movement of species between these regions occurred either over water across the Indian Ocean, possibly using island stepping-stones, or through the Arabian Peninsula during periods of suitable environment. Each dispersal event defines the origin of a pair of same-aged sister clades in the two regions.If each diversifying clade filled a certain part of ecological space to a carrying capacity for species, after which diversification slowed, the sizes of clades filling this space would level off over time (26). Furthermore, the number of species per sister clade, particularly among older clades that have filled ecological space, might be correlated between regions, with species richness reflecting the ecological space available to each of the sister lineages (27). Finally, for those dispersal events whose directionality can be inferred, the rate of diversification should be higher, leading to larger clade size compared between sister lineages, in the newly colonized region, which initially would have fewer close (and ecologically similar) relatives of the ancestral species.We include all species of passerine birds (Passeriformes) and, separately, species in nonpasserine orders, of small, terrestrial birds, in the Oriental and African biogeographic regions (SI Appendix, section S1). The passerine avifauna of these regions accumulated from several sources over most of the Cenozoic Era (28, 29), with an old Gondwanan clade of suboscine passerines diversifying in tropical Africa and southern Asia early in the Tertiary, followed by radiations of core corvoid and passerid oscine passerines out of Australia during the early to mid-Cenozoic, through Wallacea to southern Asia, or directly across the Indian Ocean to Africa (30, 31). Thus, the diversification of sister clades in the African and Oriental regions takes place against a background of an increasing number of lineages of modern passerine birds as a whole within the region. Nonpasserine orders of terrestrial birds are likely to have diversified earlier within these regions (32) and perhaps were replaced to some extent by the passerines.Characteristics of a sample of clades include the distribution of node ages and the relationship between clade size and stem age, as well as the distribution of clade sizes regardless of age, including the proportion of clades that contain a single species. Any process-based model of diversification should be judged by how well it reproduces these characteristics. We use these criteria to evaluate simulations in which we attempt to reconstruct the underlying diversification process.     

Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs

To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot‐Marie‐Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light‐chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype.