Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are ...consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.
The development of bone‐rebuilding anabolic agents for potential use in the treatment of bone loss conditions, such as osteoporosis, has been a long‐standing goal. Genetic studies in humans and mice ...have shown that the secreted protein sclerostin is a key negative regulator of bone formation, although the magnitude and extent of sclerostin's role in the control of bone formation in the aging skeleton is still unclear. To study this unexplored area of sclerostin biology and to assess the pharmacologic effects of sclerostin inhibition, we used a cell culture model of bone formation to identify a sclerostin neutralizing monoclonal antibody (Scl‐AbII) for testing in an aged ovariectomized rat model of postmenopausal osteoporosis. Six‐month‐old female rats were ovariectomized and left untreated for 1 yr to allow for significant estrogen deficiency‐induced bone loss, at which point Scl‐AbII was administered for 5 wk. Scl‐AbII treatment in these animals had robust anabolic effects, with marked increases in bone formation on trabecular, periosteal, endocortical, and intracortical surfaces. This not only resulted in complete reversal, at several skeletal sites, of the 1 yr of estrogen deficiency‐induced bone loss, but also further increased bone mass and bone strength to levels greater than those found in non‐ovariectomized control rats. Taken together, these preclinical results establish sclerostin's role as a pivotal negative regulator of bone formation in the aging skeleton and, furthermore, suggest that antibody‐mediated inhibition of sclerostin represents a promising new therapeutic approach for the anabolic treatment of bone‐related disorders, such as postmenopausal osteoporosis.
Introduction: Sclerosteosis is a rare high bone mass genetic disorder in humans caused by inactivating mutations in SOST, the gene encoding sclerostin. Based on these data, sclerostin has emerged as ...a key negative regulator of bone mass. We generated SOST knockout (KO) mice to gain a more detailed understanding of the effects of sclerostin deficiency on bone.
Materials and Methods: Gene targeting was used to inactivate SOST and generate a line of SOST KO mice. Radiography, densitometry, μCT, histomorphometry, and mechanical testing were used to characterize the impact of sclerostin deficiency on bone in male and female mice. Comparisons were made between same sex KO and wildtype (WT) mice.
Results: The results for male and female SOST KO mice were similar, with differences only in the magnitude of some effects. SOST KO mice had increased radiodensity throughout the skeleton, with general skeletal morphology being normal in appearance. DXA analysis of lumbar vertebrae and whole leg showed that there was a significant increase in BMD (>50%) at both sites. μCT analysis of femur showed that bone volume was significantly increased in both the trabecular and cortical compartments. Histomorphometry of trabecular bone revealed a significant increase in osteoblast surface and no significant change in osteoclast surface in SOST KO mice. The bone formation rate in SOST KO mice was significantly increased for trabecular bone (>9‐fold) at the distal femur, as well as for the endocortical and periosteal surfaces of the femur midshaft. Mechanical testing of lumbar vertebrae and femur showed that bone strength was significantly increased at both sites in SOST KO mice.
Conclusions: SOST KO mice have a high bone mass phenotype characterized by marked increases in BMD, bone volume, bone formation, and bone strength. These results show that sclerostin is a key negative regulator of a powerful, evolutionarily conserved bone formation pathway that acts on both trabecular and cortical bone.
Most agronomic traits in rice are complex and polygenic. The identification of quantitative trait loci (QTL) for grain length is an important objective of rice genetic research and breeding programs.
...Herein, we identified 99 QTL for grain length by GWAS based on approximately 10 million single nucleotide polymorphisms from 504 cultivated rice accessions (Oryza sativa L.), 13 of which were validated by four linkage populations and 92 were new loci for grain length. We scanned the Ho (observed heterozygosity per locus) index of coupled-parents of crosses mapping the same QTL, based on linkage and association mapping, and identified two new genes for grain length. We named this approach as Ho-LAMap. A simulation study of six known genes showed that Ho-LAMap could mine genes rapidly across a wide range of experimental variables using deep-sequencing data. We used Ho-LAMap to clone a new gene, OsLG3, as a positive regulator of grain length, which could improve rice yield without influencing grain quality. Sequencing of the promoter region in 283 rice accessions from a wide geographic range identified four haplotypes that seem to be associated with grain length. Further analysis showed that OsLG3 alleles in the indica and japonica evolved independently from distinct ancestors and low nucleotide diversity of OsLG3 in indica indicated artificial selection. Phylogenetic analysis showed that OsLG3 might have much potential value for improvement of grain length in japonica breeding.
The results demonstrated that Ho-LAMap is a potential approach for gene discovery and OsLG3 is a promising gene to be utilized in genomic assisted breeding for rice cultivar improvement.
Little research has been conducted on the human immunodeficiency virus (HIV) epidemic and the sexual intercourse habits of men who have sex with men (MSM) in crowded places, both locally and abroad. ...This study conducted a survey of MSM in different locales of Inner Mongolia to provide a reference for developing strategies or measures to prevent and control HIV among this understudied population.
We conducted a cross-sectional survey of men aged 18 years and older at different venues popular among MSM in Inner Mongolia. Between April and July 2012, MSM volunteered to participate in this study, receive HIV/syphilis testing, and complete a questionnaire about their behavior. A total of 1611 MSM participated. Participants signed a voluntary informed consent form, completed an anonymous questionnaire and were tested for HIV and syphilis antibodies.
Of the 1611 MSM surveyed, 6.83 and 23.65 % had HIV and syphilis, respectively, and the co-infection rate was 3.17 %. Sociodemographic factors such as age, culture, marital status, knowledge of acquired immune deficiency syndrome (AIDS) transmission, and peer education significantly differed between venues (P < 0.01). MSM who were under 22 years, 23-35 years, and over 36 years primarily contacted their potential partners online, at bars/other (streetwalkers), and at public baths/parks, respectively. MSM partners found in bars, in public baths, in parks and online were primarily high school students and technical secondary school students. MSM who were streetwalkers or cross-dressing male sex workers primarily had junior middle school education levels or below. Married MSM primarily had intercourse in public baths and parks, and MSM who had intercourse in public baths and parks also reported the greatest proportions of intercourse with women (39.1 and 35.0 %, respectively). Furthermore, MSM who had intercourse in parks reported having the most anal sex with same-sex partners and unprotected intercourse in the past 6 months. Unprotected intercourse with women in the past 6 months was also common among MSM who met partners in bathhouses or online. MSM were most likely to have anal sex with other men in public baths. MSM who had intercourse in bars were the least likely to have used a condom with female partners in the past 6 months. The culture of the MSM who had frequent intercourse with streetwalkers and cross-dressing male sex workers did not predict behavior.
This study indicated that AIDS-related risky behaviors as well as HIV and syphilis infection were associated with the different locations frequented by MSM. When developing intervention strategies for AIDS, it is better to conduct targeted health education and behavioral interventions at bars/online for MSM aged 23-35 years and at public baths/parks for MSM over 36 years. Additionally, the current survey showed that information on AIDS/sexually transmitted diseases (STDs) must be popularized to reach streetwalkers and cross-dressing male sex workers, whose mobility limits their attainment of higher levels of health education.
Roots are a vital organ for absorbing soil moisture and nutrients and influence drought resistance. The identification of quantitative trait loci (QTLs) with molecular markers may allow the ...estimation of parameters of genetic architecture and improve root traits by molecular marker-assisted selection (MAS). A mapping population of 120 recombinant inbred lines (RILs) derived from a cross between japonica upland rice 'IRAT109' and paddy rice 'Yuefu' was used for mapping QTLs of developmental root traits. All plant material was grown in PVC-pipe. Basal root thickness (BRT), root number (RN), maximum root length (MRL), root fresh weight (RFW), root dry weight (RDW) and root volume (RV) were phenotyped at the seedling (I), tillering (II), heading (III), grain filling (IV) and mature (V) stages, respectively. Phenotypic correlations showed that BRT was positively correlated to MRL at the majority of stages, but not correlated with RN. MRL was not correlated to RN except at the seedling stage. BRT, MRL and RN were positively correlated to RFW, RDW and RV at all growth stages. QTL analysis was performed using QTLMapper 1.6 to partition the genetic components into additive-effect QTLs, epistatic QTLs and QTL-by-year interactions (Q x E) effect. The results indicated that the additive effects played a major role for BRT, RN and MRL, while for RFW, RDW and RV the epistatic effects showed an important action and Q x E effect also played important roles in controlling root traits. A total of 84 additive-effect QTLs and 86 pairs of epistatic QTLs were detected for the six root traits at five stages. Only 12 additive QTLs were expressed in at least two stages. This indicated that the majority of QTLs were developmental stage specific. Two main effect QTLs, brt9a and brt9b, were detected at the heading stage and explained 19% and 10% of the total phenotypic variation in BRT without any influence from the environment. These QTLs can be used in breeding programs for improving root traits.
•Testcrosses between 57 introgression lines and four male sterile lines were used to dissect the genetic basis of combining ability.•Thirty-two main- effect QTL and 92 epistatic QTL pairs were ...identified for GCA of grain yield and eight related traits.•Forty-five main- effect QTL were identified for SCA of grain yield and eight related traits.•The Shuhui527 alleles at the markers RM508 and RM587 on chromosome 6 played important roles in making Shuhui527 a key parent in hybrid rice breeding.•The ZDZ057 alleles at markers RM4584 on chromosome 7 and RM224 on chromosome 11 could be used to improve GCA for GY of Shuhui527.
Combining ability analysis is commonly used to obtain information for designing more efficient hybrid breeding strategies in rice. However, genetic basis of combining ability is less studied. Two hundred and twenty eight testcross combinations developed by crossing 57 introgression lines derived from two donor parents with four types of widely used male sterile lines were used to conduct combining ability analysis and dissect the genetic basis of combining ability for grain yield and eight related traits. The variances of general combining ability (GCA) and special combining ability (SCA) for all nine traits were highly significant in both years. A total of 32 and 45 main effect QTL controlling GCA and SCA for the nine traits were identified across the two years, respectively. Only six QTL were commonly identified for GCA and SCA. Twenty one of the GCA QTL had the positive alleles from the recurrent parent, Shuhui527. Only 11 and six QTL were commonly detected in the two years, and in the two populations classified by the donor parents, respectively. As for SCA, 22 out of the 45 QTL were commonly identified in the two years and 25 QTL had positive effects. A total of 92 epistatic QTL pairs for GCA were identified. The Shuhui527 alleles at the markers RM508 and RM587 on chromosome 6 had the largest effects on GCA for GY and thus played important roles in making Shuhui527 a key parent in hybrid rice breeding. The ZDZ057 alleles at markers RM4584 on chromosome 7 and RM224 on chromosome 11 could be used to further improve GY GCA of Shuhui527.
MCF-7/AdrVp is a multidrug-resistant human breast cancer subline that displays an ATP-dependent reduction in the intracellular accumulation of anthracycline anticancer drugs in the absence of ...overexpression of known multidrug resistance transporters such as P glycoprotein or the multidrug resistance protein. RNA fingerprinting led to the identification of a 2.4-kb mRNA that is overexpressed in MCF-7/AdrVp cells relative to parental MCF-7 cells. The mRNA encodes a 663-aa member of the ATP-binding cassette superfamily of transporters that we term breast cancer resistance protein (BCRP). Enforced expression of the full-length BCRP cDNA in MCF-7 breast cancer cells confers resistance to mitoxantrone, doxorubicin, and daunorubicin, reduces daunorubicin accumulation and retention, and causes an ATP-dependent enhancement of the efflux of rhodamine 123 in the cloned transfected cells. BCRP is a xenobiotic transporter that appears to play a major role in the multidrug resistance phenotype of MCF-7/AdrVp human breast cancer cells.
Identification of metabolites responsible for tolerance to low nitrogen availability (low-N) will aid in the genetic improvement of rice yield under nitrogen deficiency. In this study, a backcross ...introgression line (G9) and its recurrent parent Shuhui 527 (SH527), which show differential responses to low-N stress, were used to identify metabolites associated with low-N tolerance in rice. Differences in metabolite contents in the leaves of G9 and SH527 at three growth stages under low-N stress were assessed by gas chromatography–mass spectrometry. Many metabolites, including amino acids and derivatives, were highly enriched in G9 compared with SH527 under the control condition, suggesting that the two genotypes had basal metabolite differences. Low-N stress induced genotype-specific as well as growth stage-dependent metabolite changes. Metabolites induced specifically in G9 that were involved in glycolysis and tricarboxylic acid metabolism were enriched at the tillering and grain filling stages, and metabolites involved in nitrogen and proline metabolism were enriched at the booting stage. Enrichment of pyroglutamate, glutamate, 2-oxoglutarate, sorbose, glycerate-2-P, and phosphoenolpyruvic acid in G9 suggests that these metabolites could be involved in low-N stress tolerance. The results presented here provide valuable information for further elucidation of the molecular mechanisms of low-N tolerance in crops.
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