Bone size is an important determinant of bone strength and is under strong genetic control.
To identify quantitative trait loci (QTL) for areal bone size variation, a large‐scale genomewide linkage scan was carried out in 451 Caucasian families.
Participants and methods
Of 4124 people with phenotypes, 3899 were genotyped with 410 microsatellite markers. Multipoint linkage analyses were carried out in the entire sample, as well as in men and women separately. Potential epistatic interactions between identified genomic regions were also assessed.
Several potentially important genomic regions were identified, such as 8q24 for hip bone size (logarithm of the ratio of the odds that two loci are linked (LOD) 3.27) and 2p24 (LOD 2.04) for spine bone size. 8q24 may also interact with 19p13 to affect hip bone size. Several sex‐specific QTL were also detected, such as 14q21 (LOD 2.94) for wrist bone size in women and 16q12 (LOD 2.19) for hip bone size in men.
Together with previous findings, this study has further delineated the genetic basis of bone size and laid a foundation for future studies to eventually elucidate the mechanisms of bone size regulation and associated fracture risks.
Investigations using Drosophila melanogaster have shown that the circadian clock gene period can influence behavioral responses to cocaine, and the mouse homologues, mPer1 and mPer2, modulate cocaine sensitization and reward. In the present study, we applied DNAzyme targeting mPer1 to interfere the expression of mPer1 in CNS in mice and studied the role of mPer1 on morphine dependence. We found that the DNAzyme could attenuate the expression of mPer1 in CNS in mice. Mice treated with DNAzyme and morphine synchronously did not show preference to the morphine-trained side, whereas the control group did. In contrast, mice treated with DNAzyme after morphine showed preference to the morphine-trained side as well as the control group did. These results indicate that drug dependence seems to be influenced at least partially by mPer1, but mPer1 cannot affect morphine dependence that has been formed.
drug dependence; DNAzyme; learning and memory; circadian; i.c.v.
Objective: To test the hypothesis that activation of peroxisome proliferator activated receptor γ (PPAR-γ) reduces experimental autoimmune myocarditis (EAM) associated with inhibitor κB (IκB) α induction, blockade of nuclear factor κB (NF-κB), and inhibition of inflammatory cytokine expression.
Methods: EAM was induced in Lewis rats by immunisation with porcine cardiac myosin. PPAR-γ activators 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) and pioglitazone (PIO) were administered to rats with EAM.
Results: Enhanced PPAR-γ expression was prominently stained in the nuclear and perinuclear regions of infiltrating inflammatory cells. Administration of 15d-PGJ2 and PIO greatly reduced the severity of myocarditis and suppressed myocardial mRNA and protein expression of inflammatory cytokines in rats with EAM. In addition, treatment with PPAR-γ activators enhanced IκB concentrations in the cytoplasmic fractions and nuclear fractions from inflammatory myocardium. Concurrently, NF-κB was greatly activated in myocarditis; this activation was blocked in the 15d-PGJ2 treated and PIO treated groups.
Conclusions: PPAR-γ may have a role in the pathophysiology of EAM. Because an increase in IκB expression and inhibition of translocation of the NF-κB subunit p65 to the nucleus in inflammatory cells correlated with the protective effects of PPAR-γ activators, these results suggest that PPAR-γ activators act sequentially through PPAR-γ activation, IκB induction, blockade of NF-κB activation, and inhibition of inflammatory cytokine expression. These results suggest that PPAR-γ activators such as 15d-PGJ2 and PIO may have the potential to modulate human inflammatory heart diseases such as myocarditis.
myocarditis; immunity; PPAR-γ; NF-κB; cytokine; inflammation
To evaluate the efficacy and safety of phacoemulsification using torsional modality with different parameter settings for hard nucleus cataract extraction.
A prospective, randomised clinical study.
A clinical practice study conducted at the Cataract Service, Zhongshan Ophthalmic Center, Sun-Yat-Sen University, and Guangzhou. One eye each from 198 consecutive patients with cataract density grade IV according to the Emery–Little system classification system, requiring phacoemulsification and intraocular lens implantation, was included. Eyes were randomly assigned to the Linear Torsional combined with Ultrasound power group (Linear Tor+US group, n = 66), 100% Fixed Torsional group (Fixed Tor group, n = 65) and conventional Ultrasound burst group (US group, n = 67). All surgeries were performed by a single experienced surgeon and outcomes evaluated by another surgeon masked to treatment. Intraoperative parameters were Ultrasound Time (UST), Cumulative Dissipated Energy (CDE) and surgical complications. Patients were examined on post-op days 1, 7 and 30. Postoperative outcomes were final best corrected visual acuity (BCVA), average central and incisional corneal thickness and central endothelial cell counts.
The mean UST was lower in the Fixed Tor group than in the US group and in the Lin US+Tor group (p⩽0.0001). The mean CDE was lower in the Lin Tor+US group and in the Fixed Tor group than in the US group (p⩽0.0001). Comparing with the two Tor group, the US group had a lower average BCVA on post-op 1, 7 (p⩽0.0001) and 30 (p>0.01), greater average central corneal and incisional thickness on days 1, 7 (p⩽0.0001) and 30 (p>0.01), and higher average corneal endothelial cell losses on day 7 and 30 days (p⩽0.0001).
Torsional combined with ultrasound power or high fixed torsional amplitude can yield more effective hard nucleus phacoemulsification than conventional ultrasound modality.
Background: Osteoporosis is a major public health problem, mainly quantified by low bone mineral density (BMD). The majority of BMD variation is determined by genetic effects. A pilot whole genome linkage scan (WGS) was previously reported in 53 white pedigrees with 630 subjects. Several genomic regions were suggested to be linked to BMD variation.
Objective: To substantiate these previous findings and detect new genomic regions.
Methods: A WGS was conducted on an extended sample where the size was almost tripled (1816 subjects from 79 pedigrees). All the subjects were genotyped with 451 microsatellite markers spaced ∼8.1 cM apart across the human genome. Two point and multipoint linkage analyses were carried out using the variance component method.
Results: The strongest linkage signal was obtained on Xq27 with two point LOD scores of 4.30 for wrist BMD, and 2.57 for hip BMD, respectively. Another important region was 11q23, which achieved a maximum LOD score of 3.13 for spine BMD in multipoint analyses, confirming the results on this region in two earlier independent studies. Suggestive linkage evidence was also found on 7p14 and 20p12.
Conclusions: Together with the findings from other studies, the current study has further delineated the genetic basis of bone mass and highlights the importance of increasing sample size to confirm linkage findings and to identify new regions of linkage.
The phonon spectrum of Ge2Sb2Te5 is a signature of its crystallographic structure and underlies the phase transition process used in memory applications. Epitaxial materials allow coherent optical phonons to be studied in femtosecond anisotropic reflectance measurements. A dominant phonon mode with frequency of 3.4 THz has been observed in epitaxial Ge2Sb2Te5 grown on GaSb(001). The dependence of signal strength upon pump and probe polarization is described by a theory of transient stimulated Raman scattering that accounts for the symmetry of the crystallographic structure through use of the Raman tensor. The 3.4 THz mode has the character of the 3 dimensional T2 mode expected for the Oh point group, confirming that the underlying crystallographic structure is cubic. New modes are observed in both Ge2Sb2Te5 and GaSb after application of large pump fluences, and are interpreted as 1 and 2 dimensional modes associated with segregation of Sb.
Tissue-specific amplification of glucocorticoid action through 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) affects the development of the metabolic syndrome. Hexose-6-phosphate dehydrogenase (H6PDH) mediates intracellular NADPH availability for 11β-HSD1 and depends on the glucose-6-phosphate transporter (G6PT). Little is known about the tissue-specific alterations of H6PDH and G6PT and their contributions to local glucocorticoid action in db/db mice.
We characterised the role of H6PDH and G6PT in pre-receptor metabolism of glucocorticoids by examining the production of the hepatic 11β-HSD1-H6PDH–G6PT system in db/db mice.
We observed that increased production of hepatic H6PDH in db/db mice was paralleled by upregulation of hepatic G6PT production and responded to elevated circulating levels of corticosterone. Treatment of db/db mice with the glucocorticoid antagonist RU486 markedly reduced production of both H6PDH and 11β-HSD1 and improved hyperglycaemia and insulin resistance. The reduction of H6PDH and 11β-HSD1 production by RU486 was accompanied by RU486-induced suppression of hepatic G6pt (also known as Slc37a4) mRNA. Incubation of mouse primary hepatocytes with corticosterone enhanced G6PT and H6PDH production with corresponding activation of 11β-HSD1 and PEPCK: effects that were blocked by RU486. Knockdown of H6pd by small interfering RNA showed effects comparable with those of RU486 for attenuating the corticosterone-induced H6PDH production and 11β-HSD1 reductase activity in these intact cells. Addition of the G6PT inhibitor chlorogenic acid to primary hepatocytes suppressed H6PDH production.
These findings suggest that increased hepatic H6PDH and G6PT production contribute to 11β-HSD1 upregulation of local glucocorticoid action that may be related to the development of type 2 diabetes.
11β-HSD1; G6PT; G6PT inhibitor; H6PDH; H6PDH siRNA; Insulin resistance; NADPH; Type 2 diabetes
In the current study, the mechanical and hypothermic damage induced by vibration and cold storage on human mesenchymal stem cells (hMSCs) stored at 2–8°C was quantified by measuring the total cell number and cell viability after exposure to vibration at 50 Hz (peak acceleration 140 m s−2 and peak displacement 1.4 mm), 25 Hz (peak acceleration 140 m s−2, peak displacement 5.7 mm), 10 Hz (peak acceleration 20 m s−2, peak displacement 5.1 mm) and cold storage for several durations. To quantify the viability of the cells, in addition to the trypan blue exclusion method, the combination of annexin V-FITC and propidium iodide was applied to understand the mode of cell death. Cell granularity and a panel of cell surface markers for stemness, including CD29, CD44, CD105 and CD166, were also evaluated for each condition. It was found that hMSCs were sensitive to vibration at 25 Hz, with moderate effects at 50 Hz and no effects at 10 Hz. Vibration at 25 Hz also increased CD29 and CD44 expression. The study further showed that cold storage alone caused a decrease in cell viability, especially after 48 h, and also increased CD29 and CD44 and attenuated CD105 expressions. Cell death would most likely be the consequence of membrane rupture, owing to necrosis induced by cold storage. The sensitivity of cells to different vibrations within the mechanical system is due to a combined effect of displacement and acceleration, and hMSCs with a longer cold storage duration were more susceptible to vibration damage, indicating a coupling between the effects of vibration and cold storage.
stem cells; mechanical stress; vibration; regenerative medicine; hypothermia; viability
The main objective of this study was to investigate the feasibility of using PharmGKB, a pharmacogenomic database, as a source of training data in combination with text of MEDLINE abstracts for a text mining approach to identification of potential gene targets for pathway-driven pharmacogenomics research. We used the manually curated relations between drugs and genes in PharmGKB database to train a support vector machine predictive model and applied this model prospectively to MEDLINE abstracts. The gene targets suggested by this approach were subsequently manually reviewed. Our quantitative analysis showed that a support vector machine classifiers trained on MEDLINE abstracts with single words (unigrams) used as features and PharmGKB relations used for supervision, achieve an overall sensitivity of 85% and specificity of 69%. The subsequent qualitative analysis showed that gene targets “suggested” by the automatic classifier were not anticipated by expert reviewers but were subsequently found to be relevant to the three drugs that were investigated: carbamazepine, lamivudine and zidovudine. Our results show that this approach is not only feasible but may also find new gene targets not identifiable by other methods thus making it a valuable tool for pathway-driven pharmacogenomics research.
pharmacogenomics; text mining; support vector machine; pathway-driven analysis; gene-drug associations; PharmGKB
Hematopoietic stem cells (HSCs) possess long-term self-renewal capacity and multipotent differentiative capacity, to maintain the hematopoietic system. Long-term hematopoietic homeostasis requires effective control of genotoxic damage to maintain HSC function and prevent propagation of deleterious mutations. Here we investigate the role of the BH3-only Bcl-2 family member Bid in the response of murine hematopoietic cells to long-term replicative stress induced by hydroxyurea (HU). The PI3-like serine/threonine kinase, ATR, initiates the DNA damage response (DDR) to replicative stress. The pro-apoptotic Bcl-2 family member, Bid, facilitates this response to replicative stress in hematopoietic cells, but the in vivo role of this DDR function of Bid has not been defined. Surprisingly, we demonstrate that long-term HU treatment expands wild-type myeloid progenitor cells (MPCs) and HSC-enriched Lin−Sca1+Kit+ (LSK) cells to maintain bone marrow function as measured by long-term competitive repopulating ability. Bid−/− MPCs demonstrate increased sensitivity to HU and are depleted. Bid−/− LSK cells demonstrate increased mobilization manifest by increased Bromodeoxyuridine (BrdU) incorporation. Bid−/− MPCs and LSK cells are relatively depleted, however, and bone marrow from Bid−/− mice demonstrates decreased long-term competitive repopulating ability in both primary and secondary transplants. We thus describe a survival function of Bid in hematopoiesis in the setting of chronic replicative stress.
Bid; DNA damage response; hematopoiesis; Bcl-2 family
Glaucoma is one of the leading causes of blindness in the world. Juvenile-onset open-angle is a subtype of glaucoma. In this context, we investigate the possible mutations in the promoter and coding regions of the CYP1B1 gene among patients suffering juvenile-onset open-angle glaucoma (JOAG).
The CYP1B1 gene was analysed for mutations in 61 unrelated Taiwanese probands with JOAG and in 100 healthy control subjects. Genomic DNA was extracted from peripheral blood leukocytes and then subjected to PCR. The amplified products were screened for base mutations by autosequence. Next, data from the two groups were compared using the χ2 test. Additionally, three-dimensional (3D) modelling of the human wild-type and p.R390H mutation was performed using SWISS-MODEL, an automated homology modelling program. Finally, the figure was prepared for the modelled structures by using the Accelrys ViewerLite 5.0 program.
Analysis results indicated two CYP1B1 mutations and five polymorphisms. The prevalence of CYP1B1 gene mutations in this study was 4.92% (3/61). The mutations included a missense mutation (p.Arg390His; 2/3) and a mutation in the 5′-untranslated region (c.1–313A>C; 1/3). Moreover, computer-assisted modelling revealed that this p.R390H mutation affects the intra-molecular interaction in the hydrogen-bonding interaction with Glu387 and Asn428, thus altering significantly the efficiency of the haem-binding and proper folding of the molecule.
As a result, the p.Arg390His mutation might affect the protein structure and, ultimately, the normal function of CYP1B1. Therefore, we suggest that the c.1169G>A (p.Arg390His) mutation of CYP1B1 may be a risk factor for the development of JOAG.
CYP1B1; polymorphism; glaucoma; JOAG; mutation
Many complex disease traits are observed to be associated with single nucleotide polymorphism (SNP) interactions. In testing small-scale SNP-SNP interactions, variable selection procedures in logistic regressions are commonly used. The empirical evidence of variable selection for testing interactions in logistic regressions is limited. This simulation study was designed to compare nine variable selection procedures in logistic regressions for testing SNP-SNP interactions. Data on 10 SNPs were simulated for 400 and 1000 subjects (case/control ratio=1). The simulated model included one main effect and two 2-way interactions. The variable selection procedures included automatic selection (stepwise, forward and backward), common 2-step selection, AIC- and BIC-based selection. The hierarchical rule effect, in which all main effects and lower order terms of the highest-order interaction term are included in the model regardless of their statistical significance, was also examined. We found that the stepwise variable selection without the hierarchical rule which had reasonably high authentic (true positive) proportion and low noise (false positive) proportion, is a better method compared to other variable selection procedures. The procedure without the hierarchical rule requires fewer terms in testing interactions, so it can accommodate more SNPs than the procedure with the hierarchical rule. For testing interactions, the procedures without the hierarchical rule had higher authentic proportion and lower noise proportion compared with ones with the hierarchical rule. These variable selection procedures were also applied and compared in a rheumatoid arthritis study.
single nucleotide polymorphisms; gene interaction; logistic model; variable selection
Low-density lipoprotein-related receptor protein 1 (LRP1) is a multi-functional endocytic receptor and signaling molecule that is expressed in adipose and the hypothalamus. Evidence for a role of LRP1 in adiposity is accumulating from animal and in vitro models, but data from human studies are limited. The study objectives were to evaluate (i) relationships between LRP1 genotype and anthropometric traits, and (ii) whether these relationships were modified by dietary fatty acids.
DESIGN AND METHODS
We conducted race/ethnic-specific meta-analyses using data from 14 studies of US and European whites and 4 of African Americans to evaluate associations of dietary fatty acids and LRP1 genotypes with body mass index (BMI), waist circumference and hip circumference, as well as interactions between dietary fatty acids and LRP1 genotypes. Seven single-nucleotide polymorphisms (SNPs) of LRP1 were evaluated in whites (N up to 42 000) and twelve SNPs in African Americans (N up to 5800).
After adjustment for age, sex and population substructure if relevant, for each one unit greater intake of percentage of energy from saturated fat (SFA), BMI was 0.104 kg m−2 greater, waist was 0.305 cm larger and hip was 0.168 cm larger (all P<0.0001). Other fatty acids were not associated with outcomes. The association of SFA with outcomes varied by genotype at rs2306692 (genotyped in four studies of whites), where the magnitude of the association of SFA intake with each outcome was greater per additional copy of the T allele: 0.107 kg m−2 greater for BMI (interaction P=0.0001), 0.267 cm for waist (interaction P=0.001) and 0.21 cm for hip (interaction P=0.001). No other significant interactions were observed.
Dietary SFA and LRP1 genotype may interactively influence anthropometric traits. Further exploration of this, and other diet x genotype interactions, may improve understanding of interindividual variability in the relationships of dietary factors with anthropometric traits.
low-density lipoprotein receptor-related protein 1; SNPs; saturated fatty acids; gene–diet interactions
Cell sheet engineering has been developed as an alternative approach to improve mesenchymal stem cell-mediated tissue regeneration. In this study, we found that vitamin C (Vc) was capable of inducing telomerase activity in periodontal ligament stem cells (PDLSCs), leading to the up-regulated expression of extracellular matrix type I collagen, fibronectin, and integrin β1, stem cell markers Oct4, Sox2, and Nanog as well as osteogenic markers RUNX2, ALP, OCN. Under Vc treatment, PDLSCs can form cell sheet structures because of increased cell matrix production. Interestingly, PDLSC sheets demonstrated a significant improvement in tissue regeneration compared with untreated control dissociated PDLSCs and offered an effective treatment for periodontal defects in a swine model. In addition, bone marrow mesenchymal stem cell sheets and umbilical cord mesenchymal stem cell sheets were also well constructed using this method. The development of Vc-mediated mesenchymal stem cell sheets may provide an easy and practical approach for cell-based tissue regeneration.
Recent rapid advances in “-omics” technologies have yielded new insights into the interaction of the oral microbiome with its host. Associations of species that are usually considered to be acid-tolerant with caries have been confirmed, while some recognized as health-associated are often present in greater proportions in the absence of caries. In addition, some newly identified bacteria have been suggested as potential contributors to the caries process. In spite of this progress, two major challenges remain. The first is that there is a great deal of heterogeneity in the phenotypic capabilities of individual species of oral bacteria. The second is that the most abundant taxa in oral biofilms display remarkable phenotypic plasticity, i.e., the bacteria associated most strongly with health or with caries can morph rapidly in response to alterations in environmental pH, carbohydrate availability and source, and oxygen tension and redox environment. However, new technologic advances coupled with “old-fashioned microbiology” are starting to erode the barriers to a more complete understanding of oral biofilm physiology and ecology, and in doing so are beginning to provide insights for the creation of novel cost-effective caries control therapies.
biofilm; 16S rRNA; acid tolerance; arginine metabolism; ecology; pH homeostasis
Long-distance migrants are, by definition, highly mobile but it is poorly understood if this leads to high rates of gene flow and an essentially panmictic global population structure. Genetic divergence in migratory species could be promoted, for example, by fidelity to distinct migratory pathways. In this study, we investigate the population genetic structure of tufted duck (Aythya fuligula), a long-distance migrant with a largely continuous breeding distribution across Eurasia. Distinct, longitudinally oriented flyways have been postulated based on geographically disjunct wintering areas and are supported by evidence from ringing data. We generated sequences of the mitochondrial control region and multi-locus microsatellite genotypes for several hundreds of samples from the European and Asian breeding and wintering grounds including some individuals infected with highly pathogenic avian influenza virus H5N1. Significant differentiation between breeding sites was observed for both marker types, but FST values were approximately 10 times higher for maternally inherited mitochondrial DNA than for biparentally transmitted nuclear markers. The genetic differentiation between the postulated European and Asian flyways was similar to that observed within continents and, in general, genetic divergence was not associated with geographic distance. Neither marker type showed evidence of genetic substructure among aggregations on the European wintering grounds. Our results suggest some breeding site fidelity, especially in females, but extensive population admixture on the wintering grounds. Several scenarios may explain the observed lack of genetic divergence between Europe and Asia including non-equilibrium conditions following a recent range expansion or contemporary gene flow across the postulated migratory divides.
bird migration; population structure; flyway; microsatellites; mitochondrial DNA; avian flu
We previously reported that marchantin M (Mar) is an active agent to induce apoptosis in human prostate cancer (PCa), but the molecular mechanisms of action remain largely unknown. Here, we demonstrate that Mar potently inhibited chymotrypsin-like and peptidyl-glutamyl peptide-hydrolyzing activities of 20S proteasome both in in vitro and intracellular systems and significantly induced the accumulation of polyubiquitinated proteins in PCa cells. The computational modeling analysis suggested that Mar non-covalently bound to active sites of proteasome β5 and β1 subunits, resulting in a non-competitive inhibition. Proteasome inhibition by Mar subsequently resulted in endoplasmic reticulum (ER) stress, as evidenced by elevated glucose-regulated protein 78 and CHOP, increased phospho-eukaryotic translation initiation factor 2α (eIF2α), splicing of X-box-binding protein-1 and dilation of the ER. However, Mar-mediated cell death was not completely impaired by a pan inhibitor of caspases. Further studies revealed that the Mar-induced cell death was greatly associated with the activation of autophagy, as indicated by the significant induction of microtubule-associated protein-1 light chain-3 beta (LC3B) expression and conversion. Electron microscopic and green fluorescent protein-tagged LC3B analyses further demonstrated the ability of autophagy induction by Mar. Time kinetic studies revealed that Mar induced a rapid and highly sustained processing of LC3B in treated cells and simultaneously decreased the expression of p62/SQSTM1. Pharmacological blockade or knockdown of LC3B and Atg5 attenuated Mar-mediated cell death. The autophagic response triggered by Mar required the activation of RNA-dependent protein kinase-like ER kinase/eIF2α and suppression of the phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin axis via preventing activation and expression of Akt. Our results identified a novel mechanism for the cytotoxic effect of Mar, which strengthens it as a potential agent in cancer chemotherapy.
marchantin M; proteasome; ER stress; autophagic cell death; prostate cancer
Erythema of rosacea is thought to result from abnormal cutaneous vasomotor activity. Brimonidine tartrate (BT) is a highly selective α2-adrenergic receptor agonist with vasoconstrictive activity.
To determine the optimal concentration and dose regimen of topical BT gel for the treatment of erythema of rosacea and to evaluate its efficacy and safety.
In study A, 122 subjects were randomized to receive a single application of BT 0·07%, 0·18%, 0·5% or vehicle. In study B (4-week treatment and 4-week follow-up), 269 subjects were randomized to receive BT 0·5% once daily, BT 0·18% once daily, vehicle once daily, BT 0·18% twice daily or vehicle twice daily. Evaluations included Clinician’s Erythema Assessment (CEA), Patient’s Self-Assessment (PSA), Chroma Meter measurements and adverse events.
In study A, a single application of topical BT gel reduced facial erythema in a dose-dependent fashion. A significant difference between BT 0·5% and vehicle in Chroma Meter redness value was observed from 30 min to 12 h after application. In study B, BT 0·5% once daily had a statistically superior success profile (defined as a two-grade improvement on both CEA and PSA over 12 h) compared with vehicle once daily on days 1, 15 and 29 (all P < 0·001). No tachyphylaxis, rebound of erythema or aggravation of other disease signs (telangiectasia, inflammatory lesions) was observed. All regimens were safe and well tolerated with similarly low incidence of adverse events.
Once-daily BT gel 0·5% is well tolerated and provides significantly greater efficacy than vehicle gel for the treatment of moderate to severe erythema of rosacea.
Association mapping of important traits of crop plants relies on first understanding the extent and patterns of linkage disequilibrium (LD) in the particular germplasm being investigated. We characterize here the genetic diversity, population structure and genome wide LD patterns in a set of asparagus bean (Vigna. unguiculata ssp. sesquipedialis) germplasm from China. A diverse collection of 99 asparagus bean and normal cowpea accessions were genotyped with 1127 expressed sequence tag-derived single nucleotide polymorphism markers (SNPs). The proportion of polymorphic SNPs across the collection was relatively low (39%), with an average number of SNPs per locus of 1.33. Bayesian population structure analysis indicated two subdivisions within the collection sampled that generally represented the ‘standard vegetable' type (subgroup SV) and the ‘non-standard vegetable' type (subgroup NSV), respectively. Level of LD (r2) was higher and extent of LD persisted longer in subgroup SV than in subgroup NSV, whereas LD decayed rapidly (0–2 cM) in both subgroups. LD decay distance varied among chromosomes, with the longest (≈5 cM) five times longer than the shortest (≈1 cM). Partitioning of LD variance into within- and between-subgroup components coupled with comparative LD decay analysis suggested that linkage group 5, 7 and 10 may have undergone the most intensive epistatic selection toward traits favorable for vegetable use. This work provides a first population genetic insight into domestication history of asparagus bean and demonstrates the feasibility of mapping complex traits by genome wide association study in asparagus bean using a currently available cowpea SNPs marker platform.
asparagus bean; association mapping; cowpea; domestication history; linkage disequilibrium; population structure
Little is known about quality-of-life (QOL) differences over time between incident ductal carcinoma in situ (DCIS) and early-stage invasive breast cancer (EIBC) cases as compared with same-aged women without breast cancer (controls). We prospectively recruited and interviewed 1096 women (16.8% DCIS, 33.3% EIBC [25.7% Stage I, 7.6% Stage IIA], 49.9% controls; mean age 58; 23.7% non-white) a mean 6.7 weeks (T1), and 6.2 (T2), 12.3 (T3), and 24.4 months (T4) after surgery (patients) or screening mammogram (controls). We tested two hypotheses: (1) DCIS patients would report lower levels of QOL compared with controls but would report similar QOL compared with EIBC patients at baseline; and (2) DCIS patients’ QOL would improve during 2-year follow-up and approach levels similar to that of controls faster than EIBC patients. We tested Hypothesis 1 using separate general linear regression models for each of the eight subscales on the RAND 36-item Health Survey, controlling for variables associated with at least one subscale at T1. Both DCIS and EIBC patients reported lower QOL at T1 than controls on all subscales (each p < .05). We tested Hypothesis 2 using generalized estimating equations to examine change in each QOL subscale over time across the three diagnostic groups adjusting for covariates. By T3, physical functioning, role limitations due to physical problems, energy/fatigue, and general health each differed significantly by diagnostic group at P < 0.05, due to larger differences between EIBC patients and controls; but DCIS patients no longer differed significantly from controls on any of the QOL subscales. At T4, EIBC patients still reported worse physical functioning (P = 0.0001) and general health (P = 0.0017) than controls, possibly due to lingering treatment effects. DCIS patients’ QOL was similar to that of controls two years after diagnosis, but some aspects of EIBC patients’ QOL remained lower.
Breast cancer; ductal carcinoma in situ (DCIS); early-stage invasive breast cancer; quality of life
To evaluate different features between benign and malignant pulmonary focal ground-glass opacity (fGGO) on multidetector CT (MDCT).
82 pathologically or clinically confirmed fGGOs were retrospectively analysed with regard to demographic data, lesion size and location, attenuation value and MDCT features including shape, margin, interface, internal characteristics and adjacent structure. Differences between benign and malignant fGGOs were analysed using a χ2 test, Fisher's exact test or Mann–Whitney U-test. Morphological characteristics were analysed by binary logistic regression analysis to estimate the likelihood of malignancy.
There were 21 benign and 61 malignant lesions. No statistical differences were found between benign and malignant fGGOs in terms of demographic data, size, location and attenuation value. The frequency of lobulation (p=0.000), spiculation (p=0.008), spine-like process (p=0.004), well-defined but coarse interface (p=0.000), bronchus cut-off (p=0.003), other air-containing space (p=0.000), pleural indentation (p=0.000) and vascular convergence (p=0.006) was significantly higher in malignant fGGOs than that in benign fGGOs. Binary logistic regression analysis showed that lobulation, interface and pleural indentation were important indicators for malignant diagnosis of fGGO, with the corresponding odds ratios of 8.122, 3.139 and 9.076, respectively. In addition, a well-defined but coarse interface was the most important indicator of malignancy among all interface types. With all three important indicators considered, the diagnostic sensitivity, specificity and accuracy were 93.4%, 66.7% and 86.6%, respectively.
An fGGO with lobulation, a well-defined but coarse interface and pleural indentation gives a greater than average likelihood of being malignant.