Molecular population genetics and gene expression analysis of duplicated CBF genes of Arabidopsis thaliana

<p>Abstract</p> <p>Background</p> <p><it>CBF/DREB </it>duplicate genes are widely distributed in higher plants and encode transcriptional factors, or CBFs, which bind a DNA regulatory element and impart responsiveness to low temperatures and dehydration.</p> <p>Results</p> <p>We explored patterns of genetic variations of <it>CBF1, -2</it>, and -<it>3 </it>from 34 accessions of <it>Arabidopsis thaliana</it>. Molecular population genetic analyses of these genes indicated that <it>CBF2 </it>has much reduced nucleotide diversity in the transcriptional unit and promoter, suggesting that <it>CBF2 </it>has been subjected to a recent adaptive sweep, which agrees with reports of a regulatory protein of <it>CBF2</it>. Investigating the ratios of K_a/K_sbetween all paired <it>CBF </it>paralogus genes, high conservation of the AP2 domain was observed, and the major divergence of proteins was the result of relaxation in two regions within the transcriptional activation domain which was under positive selection after <it>CBF </it>duplication. With respect to the level of <it>CBF </it>gene expression, several mutated nucleotides in the promoters of <it>CBF3 </it>and <it>-1 </it>of specific ecotypes might be responsible for its consistently low expression.</p> <p>Conclusion</p> <p>We concluded from our data that important evolutionary changes in <it>CBF1, -2</it>, and -<it>3 </it>may have primarily occurred at the level of gene regulation as well as in protein function.</p

Genetic Analysis of Floral Symmetry Transition in African Violet Suggests the Involvement of Trans-acting Factor for CYCLOIDEA Expression Shifts

With the growing demand for its ornamental uses, the African violet (Saintpaulia ionantha) has been popular owing to its variations in color, shape and its rapid responses to artificial selection. Wild type African violet (WT) is characterized by flowers with bilateral symmetry yet reversals showing radially symmetrical flowers such as dorsalized actinomorphic (DA) and ventralized actinomorphic (VA) peloria are common. Genetic crosses among WT, DA, and VA revealed that these floral symmetry transitions are likely to be controlled by three alleles at a single locus in which the levels of dominance are in a hierarchical fashion. To investigate whether the floral symmetry gene was responsible for these reversals, orthologs of CYCLOIDEA (CYC) were isolated and their expressions correlated to floral symmetry transitions. Quantitative RT-PCR and in situ results indicated that dorsal-specific SiCYC1s expression in WT S. ionantha (SCYC1A and SiCYC1B) shifted in DA with a heterotopically extended expression to all petals, but in VA, SiCYC1s' dorsally specific expressions were greatly reduced. Selection signature analysis revealed that the major high-expressed copy of SCYC1A had been constrained under purifying selection, whereas the low-expressed helper SiCYC1B appeared to be relaxed under purifying selection after the duplication into SCYC1A and SiCYC1B. Heterologous expression of SCYC1A in Arabdiopsis showed petal growth retardation which was attributed to limited cell proliferation. While expression shifts of SCYC1A and SiCYC1B correlate perfectly to the resulting symmetry phenotype transitions in F1s of WT and DA, there is no certain allelic combination of inherited SiCYC1s associated with specific symmetry phenotypes. This floral transition indicates that although the expression shifts of SCYC1A/1B are responsible for the two contrasting actinomorphic reversals in African violet, they are likely to be controlled by upstream trans-acting factors or epigenetic regulations

18F-FDG PET/CT-based gross tumor volume definition for radiotherapy in head and neck Cancer: a correlation study between suitable uptake value threshold and tumor parameters

<p>Abstract</p> <p>Background</p> <p>To define a suitable threshold setting for gross tumor volume (GTV) when using ¹⁸Fluoro-deoxyglucose positron emission tomography and computed tomogram (PET/CT) for radiotherapy planning in head and neck cancer (HNC).</p> <p>Methods</p> <p>Fifteen HNC patients prospectively received PET/CT simulation for their radiation treatment planning. Biological target volume (BTV) was derived from PET/CT-based GTV of the primary tumor. The BTVs were defined as the isodensity volumes when adjusting different percentage of the maximal standardized uptake value (SUVmax), excluding any artifact from surrounding normal tissues. CT-based primary GTV (C-pGTV) that had been previously defined by radiation oncologists was compared with the BTV. Suitable threshold level (sTL) could be determined when BTV value and its morphology using a certain threshold level was observed to be the best fitness of the C-pGTV. Suitable standardized uptake value (sSUV) was calculated as the sTL multiplied by the SUVmax.</p> <p>Results</p> <p>Our result demonstrated no single sTL or sSUV method could achieve an optimized volumetric match with the C-pGTV. The sTL was 13% to 27% (mean, 19%), whereas the sSUV was 1.64 to 3.98 (mean, 2.46). The sTL was inversely correlated with the SUVmax [sTL = -0.1004 Ln (SUVmax) + 0.4464; R²= 0.81]. The sSUV showed a linear correlation with the SUVmax (sSUV = 0.0842 SUVmax + 1.248; R²= 0.89). The sTL was not associated with the value of C-pGTVs.</p> <p>Conclusion</p> <p>In PET/CT-based BTV for HNC, a suitable threshold or SUV level can be established by correlating with SUVmax rather than using a fixed threshold.</p

Impact of body-mass factors on setup displacement in patients with head and neck cancer treated with radiotherapy using daily on-line image guidance

BACKGROUND: To determine the impact of body-mass factors (BMF) before radiotherapy and changes during radiotherapy on the magnitude of setup displacement in patients with head and neck cancer (HNC). METHODS: The clinical data of 30 patients with HNC was analyzed using the alignment data from daily on-line on-board imaging from image-guided radiotherapy. BMFs included body weight, body height, and the circumference and bilateral thickness of the neck. Changes in the BMFs during treatment were retrieved from cone beam computed tomography at the 10th and 20th fractions. Setup errors for each patient were assessed by systematic error (SE) and random error (RE) through the superior-inferior (SI), anterior-posterior (AP), and medial-lateral (ML) directions, and couch rotation (CR). Using the median values of the BMFs as a cutoff, the impact of the factors on the magnitude of displacement was assessed by the Mann–Whitney U test. RESULTS: A higher body weight before radiotherapy correlated with a greater AP-SE (p = 0.045), SI-RE (p = 0.023), and CR-SE (p = 0.033). A longer body height was associated with a greater SI-RE (p = 0.002). A performance status score of 1 or 2 was related to a greater AP-SE (p = 0.043), AP-RE (p = 0.015), and SI-RE (p = 0.043). Among the ratios of the BMFs during radiotherapy, the values at the level of mastoid tip at the 20(th) fraction were associated with greater setup errors. CONCLUSIONS: To reduce setup errors in patients with HNC receiving RT, the use of on-line image-guided radiotherapy is recommended for patients with a large body weight or height, and a performance status score of 1–2. In addition, adaptive planning should be considered for those who have a large reduction ratio in the circumference (<1) and thickness (<0.94) over the level of the mastoid tip during the 20(th) fraction of treatment

Morphological and Molecular Defects in Human Three-Dimensional Retinal Organoid Model of X-Linked Juvenile Retinoschisis

X-linked juvenile retinoschisis (XLRS), linked to mutations in the RS1 gene, is a degenerative retinopathy with a retinal splitting phenotype. We generated human induced pluripotent stem cells (hiPSCs) from patients to study XLRS in a 3D retinal organoid in vitro differentiation system. This model recapitulates key features of XLRS including retinal splitting, defective retinoschisin production, outer-segment defects, abnormal paxillin turnover, and impaired ER-Golgi transportation. RS1 mutation also affects the development of photoreceptor sensory cilia and results in altered expression of other retinopathy-associated genes. CRISPR/Cas9 correction of the disease-associated C625T mutation normalizes the splitting phenotype, outer-segment defects, paxillin dynamics, ciliary marker expression, and transcriptome profiles. Likewise, mutating RS1 in control hiPSCs produces the disease-associated phenotypes. Finally, we show that the C625T mutation can be repaired precisely and efficiently using a base-editing approach. Taken together, our data establish 3D organoids as a valid disease model

Multi-parametric neuroimaging evaluation of cerebrotendinous xanthomatosis and its correlation with neuropsychological presentations

<p>Abstract</p> <p>Background</p> <p>Cerebrotendinous xanthomatosis (CTX) is a rare genetic disorder. Recent studies show that brain damage in CTX patients extends beyond the abnormalities observed on conventional magnetic resonance imaging (MRI). We studied the MRI and ^{99 m}Tc-ethyl cysteinate dimer single photon emission computed tomography (SPECT) findings of CTX patients and made a correlation with the neuropsychological presentations.</p> <p>Methods</p> <p>Diffusion tensor imaging (DTI) and 3D T1-weighted images of five CTX patients were compared with 15 age-matched controls. Voxel-based morphometry (VBM) was use to delineate gray matter (GM) and white matter (WM) volume loss. Fractional anisotropy (FA), mean diffusivity (MD), and eigenvalues derived from DTI were used to detect WM changes and correlate with neuropsychological results. SPECT functional studies were used to correlate with GM changes.</p> <p>Results</p> <p>Cognitive results showed that aside from moderate mental retardation, the patient group performed worse in all cognitive domains. Despite the extensive GM atrophy pattern, the cerebellum, peri-Sylvian regions and parietal-occipital regions were correlated with SPECT results. WM atrophy located in the peri-dentate and left cerebral peduncle areas corresponded with changes in diffusion measures, while axial and radial diffusivity suggested both demyelinating and axonal changes. Changes in FA and MD were preceded by VBM in the corpus callosum and corona radiata. Cognitive results correlated with FA changes.</p> <p>Conclusion</p> <p>In CTX, GM atrophy affected the perfusion patterns. Changes in WM included atrophy, and axonal changes with demyelination. Disconnection of major fiber tracts among different cortical regions may contribute to cognitive impairment.</p

Etiological Analysis of Neurodevelopmental Disabilities: Single-Center Eight-Year Clinical Experience in South China

Etiology determination of neurodevelopmental disabilities (NDDs) currently remains a worldwide common challenge on child health. We herein reported the etiology distribution feature in a cohort of 285 Chinese patients with NDDs. Although concrete NDD etiologies in 48.4% of the total patients could not be identified, genetic diseases (with the proportion of 35.8% in the total cases) including inborn errors of metabolism (IEM) and congenital dysmorphic diseases, constituted the commonest etiology category for NDDs in this study. The two key experimental technologies in pediatric metabolomics, gas chromatography-mass spectrometry (GC-MS), and tandem mass spectrometry (MS-MS), proved to be substantially helpful for the exploration of the NDD etiologies in this clinical investigation. The findings in this paper provided latest epidemiologic information on the etiology distribution of NDDs in Chinese, and the syndromic NDDs caused by citrin deficiency and the novel chromosomal karyotype, respectively, further expanded the etiology spectrum of NDDs

Origin, Transport, and Vertical Distribution of Atmospheric Polluntants over the Northern Sourth China Sea During the 7-SEAS-Dongsha Experiment

During the spring of 2010, comprehensive in situ measurements were made for the first time on a small atoll (Dongsha Island) in the northern South China Sea (SCS), a key region of the 7-SEAS (the Seven South East Asian Studies) program. This paper focuses on characterizing the source origins, transport processes, and vertical distributions of the Asian continental outflows over the region, using measurements including mass concentration, optical properties, hygroscopicity, and vertical distribution of the aerosol particles, as well as the trace gas composition. Cluster analysis of backward trajectories classified 52% of the air masses arriving at ground level of Dongsha Island as having a continental origin, mainly from northern China to the northern SCS, passing the coastal area and being confined in the marine boundary layer (0-0.5 km). Compared to aerosols of oceanic origin, the fine mode continental aerosols have a higher concentration, extinction coefficient, and single-scattering albedo at 550 nm (i.e., 19 vs. 14 microg per cubic meter in PM(sub 2.5); 77 vs. 59 M per meter in beta(sub e); and 0.94 vs. 0.90 in omega, respectively). These aerosols have a higher hygroscopicity (f at 85% RH = 2.1) than those in the upwind inland regions, suggesting that the aerosols transported to the northern SCS were modified by the marine environment. In addition to the near-surface aerosol transport, a significant upper-layer (3-4 km) transport of biomass-burning aerosols was observed. Our results suggest that emissions from both China and Southeast Asia could have a significant impact on the aerosol loading and other aerosol properties over the SCS. Furthermore, the complex vertical distribution of aerosols-coinciding-with-clouds has implications for remote-sensing observations and aerosol-cloud-radiation interactions