Advanced Application of Diffusion Kurtosis Imaging

Diffusion tensor imaging (DTI) has become a standard procedure in clinical routine as well as research as it enables the reconstruction and visualization of fiber tracts in the human brain. Due to the simplified assumption the tensor model – a Gaussian distribution of the diffusion – it typically fails to provide neither accurate spatial mapping nor quantification of crossing or kissing fibers. A clinically feasible development might be diffusion kurtosis imaging (DKI), an extension of DTI also integrating non-Gaussian distribution diffusion processes and thereby shall overcome some of its limitations. The potential DKI will be evaluated in case of the detection of the interhemispheric asymmetry of the white matter in healthy volunteers (n = 20), as well as the analysis of tumor-related impairments of fiber tracts and their correlation with neurological deficits in patients (n = 13) diagnosed with glioma. In order to analyze interhemispheric asymmetry across the whole brain, especially of nine large fiber tracts, tract-based spatial statistics (TBSS) analysis was performed using DTI- and DKI-based parameters, a laterality index was calculated for asymmetries and DTI- and DKI-based results were compared. With regard to fractional anisotropy as marker of integrity, asymmetry was found for all nine fiber tracts based on DTI and seven tracts based on DKI. For mean diffusivity, asymmetries were found for three (DTI) and two (DKI) fiber tracts. Regarding mean kurtosis, asymmetry was found in one tract. The interhemispheric asymmetry thereby varied in anatomical location as well as in cluster size. Only small parts of the tracts were affected. A comparison of DTI and DKI showed significantly higher fractional anisotropy and mean diffusivity based on DKI compared to DTI. Gender and handedness did not seem to have any influence. For the assessment of tumor-related changes of fiber tracts in patients diagnosed with glioma, especially in relation to pre-existing and postoperative neurological deficits (hemiparesis, aphasia), templates for the corticospinal tract and the arcuate fasciculus were created based on DTI- and DKI-derived parameters, respectively. The corticospinal tract and the arcuate fasciculus were reconstructed for each patient and the associated parametric maps were projected onto the templates. Based on this, alterations along the tracts could be identified and quantified. Alterations were found on fiber tracts regardless of the spatial proximity to the lesion. There was a correlation between alterations based on fractional anisotropy, mean diffusivity and mean kurtosis. Increased mean diffusivity was associated with alteration in mean kurtosis, a decreased fractional anisotropy was found concurrent with a likewise decreased mean kurtosis. In the case of pre-existing neurological deficits (hemiparesis, aphasia) with regard to the changes along the fiber tracts (corticospinal tract, left arcuate fasciculus), most often increased mean diffusivity and altered mean kurtosis was found. Applying this pattern for prediction of corresponding postoperative neurological deficits a sensitivity of 75.0% and a specificity of 87.5% was achieved. DKI seems to more precisely estimated and depict the underlying microstructure in comparison to DTI. Thereby, in pathological cases especially the mean kurtosis seems to be of special interest. A combination of DTI- and DKI based parameters, particularly with regard to its clinical usability and value, offers great potential in clinical routine

Trade linkages and growth in South Africa: an SVAR analysis

This paper investigates the vulnerability of South Africa to the shocks that originate from its major trading partners over time using a structural vector autoregressive framework. We examine the impact of shocks emanating from the EU, the US, China, Japan, India and Brazil on South Africa’s output growth through both direct and indirect trade linkages, by considering the changing trade patterns from 1996 to 2017. The results suggest that the South African economy has become more integrated with emerging economies. Furthermore, China has increased its impact on the output growth of the other sample economies through trade linkages, which implies that developments in China are of increasing importance to other economies. The US and the EU are still dominated in propagating shocks despite their declining impact on the output growth of other economies in this sample

Involvement of TNF-alpha and IL-10 in breast cancer and patient survival

Purpose: To investigate the involvement of tumor necrosis factor α (TNF-α) and interleukin 10 (IL-10) in the pathogenesis of breast cancer in vivo as well as the activity of ten Chinese herbal compounds in human breast cancer (MCF-7) cell proliferation in vitro.Methods: In the in vivo study, the association of serum TNF-α and IL-10 with breast cancer cell invasiveness and prognosis was determined in female patients (n = 192) with breast cancer, while in the in vitro study, ten herbal Chinese compounds were screened for their effectiveness against MCF-7 cells. The levels of TNF-α, IL-10, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor-2 (HER2/neu) were assayed using their respective enzyme-linked immunosorbent assay (ELISA) kits. Molecular docking was used to determine the lead compound(s) that can effectively inhibit TNF-α and IL-10.Results: Raised serum levels of TNF-α and IL-10 were significantly associated with breast cancer cell invasiveness and poor prognosis (p < 0.05). Moreover, there was a strong association between breast cancer prognosis and the expression levels of ER, PR and HER2/neu. Serum TNF-α and IL-10 levels were significantly elevated in stages II and III patients and in those with lymph node metastasis. Treatment of MCF-7 cells with the herbal compounds significantly reduced the synthesis and release of TNF-α and IL-10 (p < 0.05). The results of molecular docking showed that baicalein and oridonin significantly inhibited TNF- α and IL-10. The two herbal compounds had the highest docking scores for inhibition of cytokines, as well as favorable interaction energies.Conclusion: These results indicate that TNF-α and IL-10 are involved in the pathogenesis of breast cancer, and that baicalein and oridonin effectively inhibit the proliferation of the cells. Keywords: Baicalein, Breast cancer, Interleukin 10, Oridonin, Tumor necrosis factor alph

Distribution of MAs.

<p>(A) The number of MAs in HERVs of the 24 human chromosomes. (B)The number of MAs per bp in HERVs of the 24 human chromosomes.</p

A computational method for prediction of matrix proteins in endogenous retroviruses

<div><p>Human endogenous retroviruses (HERVs) encode active retroviral proteins, which may be involved in the progression of cancer and other diseases. Matrix protein (MA), in group-specific antigen genes (<i>gag</i>) of retroviruses, is associated with the virus envelope glycoproteins in most mammalian retroviruses and may be involved in virus particle assembly, transport and budding. However, the amount of annotated MAs in ERVs is still at a low level so far. No computational method to predict the exact start and end coordinates of MAs in gags has been proposed yet. In this paper, a computational method to identify MAs in ERVs is proposed. A divide and conquer technique was designed and applied to the conventional prediction model to acquire better results when dealing with gene sequences with various lengths. Initiation sites and termination sites were predicted separately and then combined according to their intervals. Three different algorithms were applied and compared: weighted support vector machine (WSVM), weighted extreme learning machine (WELM) and random forest (RF). <i>G</i> − <i>mean</i> (geometric mean of sensitivity and specificity) values of initiation sites and termination sites under 5-fold cross validation generated by random forest models are 0.9869 and 0.9755 respectively, highest among the algorithms applied. Our prediction models combine RF & WSVM algorithms to achieve the best prediction results. 98.4% of all the collected ERV sequences with complete MAs (125 in total) could be predicted exactly correct by the models. 94,671 HERV sequences from 118 families were scanned by the model, 104 new putative MAs were predicted in human chromosomes. Distributions of the putative MAs and optimizations of model parameters were also analyzed. The usage of our predicting method was also expanded to other retroviruses and satisfying results were acquired.</p></div

Stilbenoids and Flavonoids from <i>Cajanus cajan</i> (L.) Millsp. and Their <i>α</i>-Glucosidase Inhibitory Activities

Two new stilbenoids, cajanstilbenoid C (1) and cajanstilbenoid D (2), together with eight other known stilbenoids (3-10) and seventeen known flavonoids (11-27), were isolated from the petroleum ether and ethyl acetate portions of the 95% ethanol extract of leaves of Cajanus cajan (L.) Millsp. The planar structures of the new compounds were elucidated by NMR and high-resolution mass spectrometry, and their absolute configurations were determined by comparison of their experimental and calculated electronic circular dichroism (ECD) values. All the compounds were assayed for their inhibitory activities against yeast α-glucosidase. The results demonstrated that compounds 3, 8-9, 11, 13, 19-21, and 24-26 had strong inhibitory activities against α-glucosidase, with compound 11 (IC50 = 0.87 ± 0.05 μM) exhibiting the strongest activity. The structure–activity relationships were preliminarily summarized. Moreover, enzyme kinetics showed that compound 8 was a noncompetitive inhibitor, compounds 11, 24-26 were anticompetitive, and compounds 9 and 13 were mixed-competitive

Motifs of residues adjacent to boundaries of MAs in ERV sequences.

<p>It shows motifs of surrounding residues of ERVs’ (A) MA initiation sites, (B) MA Termination sites.</p

Prediction performance on sequences with intact MAs from different retrovirus genuses.

<p>Prediction performance on sequences with intact MAs from different retrovirus genuses.</p