Salt Content Distribution and Paleoclimatic Significance of the Lop Nur “Ear” Feature: Results from Analysis of EO-1 Hyperion Imagery

Lop Nur, a playa lake located on the eastern margin of Tarim Basin in northwestern China, is famous for the “Ear” feature of its salt crust, which appears in remote-sensing images. In this study, partial least squares (PLS) regression was used to estimated Lop Nur playa salt-crust properties, including total salt, Ca2+, Mg2+, Na+, Si2+, and Fe2+ using laboratory hyperspectral data. PLS results for laboratory-measured spectra were compared with those for resampled laboratory spectra with the same spectral resolution as Hyperion using the coefficient of determination (R2) and the ratio of standard deviation of sample chemical concentration to root mean squared error (RPD). Based on R2 and RPD, the results suggest that PLS can predict Ca2+ using Hyperion reflectance spectra. The Ca2+ distribution was compared to the “Ear area” shown in a Landsat Thematic Mapper (TM) 5 image. The mean value of reflectance from visible bands for a 14 km transversal profile to the “Ear area” rings was extracted with the TM 5 image. The reflectance was used to build a correlation with Ca2+ content estimated with PLS using Hyperion. Results show that the correlation between Ca2+ content and reflectance is in accordance with the evolution of the salt lake. Ca2+ content variation was consistent with salt deposition. Some areas show a negative correlation between Ca2+ content and reflectance, indicating that there could have been a small-scale temporary runoff event under an arid environmental background. Further work is needed to determine whether these areas of small-scale runoff are due to natural (climate events) or human factors (upstream channel changes

Pathological Tau From Alzheimer’s Brain Induces Site-Specific Hyperphosphorylation and SDS- and Reducing Agent-Resistant Aggregation of Tau in vivo

Neurofibrillary tangles (NFTs) made up of hyperphosphorylated tau are a histopathological hallmark of Alzheimer’s disease (AD) and related tauopathies. Hyperphosphorylation of tau is responsible for its loss of normal physiological function, gain of toxicity and its aggregation to form NFTs. Injection of misfolded tau seeds into mouse brain induces tau aggregation, but the nature of tau phosphorylation in pathologic tau seeded pathology is unclear. In the present study, we injected hyperphosphorylated and oligomeric tau isolated from AD brain (AD P-tau) into hippocampus of human tau transgenic mice and found that in addition to tau aggregation/pathology, tau was hyperphosphorylated at Ser202/Thr205, Thr212, Ser214, Thr217, Ser262, and Ser422 in AD P-tau injected hippocampus and at Ser422 in the contralateral hippocampus and in the ipsilateral cortex. AD P-tau-induced AD-like high molecular weight aggregation of tau that was SDS- and reducing agent-resistant and site-specifically hyperphosphorylated in the ipsilateral hippocampus. There were no detectable alterations in levels of tau phosphatases or tau kinases in AD P-tau-injected brains. Furthermore, we found that hyperphosphorylated tau was easier to be captured by AD P-tau and that aggregated tau was more difficult to be dephosphorylated than the non-aggregated tau by protein phosphatase 2A (PP2A). Based on these findings, we speculate that AD P-tau seeds hyperphosphorylated tau to form aggregates, which resist to the dephosphorylation by PP2A, resulting in hyperphosphorylation and pathology of tau

Efficacy and safety of the compound Chinese medicine SaiLuoTong in vascular dementia: A randomized clinical trial

Introduction: No licensed medications are available to treat vascular dementia (VaD). Methods: Patients were randomly assigned to experimental groups (SaiLuoTong [SLT] 360 or 240 mg for groups A and B for 52 weeks, respectively) or placebo group (SLT 360 mg and 240 mg for group C only from weeks 27 to 52, respectively). Results: Three hundred twenty-five patients were included in final analysis. At week 26, the difference in VaD Assessment Scale-cognitive subscale scores was 2.67 (95% confidence interval, 1.54 to 3.81) for groups A versus C, and 2.48 (1.34 to 3.62) for groups B versus C (both Discussion: This study suggests that SLT is effective for treatment of VaD, and this compound Chinese medicine may represent a better choice to treat VaD

Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis Through miR-3546/SOX4/Survivin Axis in Rat Thy-1 Nephritis

Background/Aims: The activation of complement system and the formation of C5b-9 complex have been confirmed in the glomeruli of patients with mesangioproliferative glomerulonephritis (MsPGN). However, the role and mechanism of C5b-9-induced injury in glomerular mesangial cell (GMC) are poorly understood. Rat Thy-1N is an animal model for studying MsPGN. It has been revealed that the attack of C5b-9 to the GMC in rat Thy-1N is sublytic, and sublytic C5b-9 can cause GMC apoptosis, but the underlying mechanism is not fully elucidated. To explore the role and regulatory mechanism of C5b-9 in MsPGN lesion, we used rat Thy-1N model and first detected the change of microRNA (miRNA) profiles both in Thy-1N rat renal tissues (in vivo) and in the cultured GMCs with sublytic C5b-9 stimulation (in vitro). Then we determined the effect of miR-3546, which increased both in vivo and in vitro, on GMC apoptosis upon sublytic C5b-9 as well as the involved mechanism. Methods: Rat Thy-1N model was established and GMCs were treated with sublytic C5b-9. The rat renal cortex and the stimulated GMCs were obtained for miRNA microarray detection. Subsequently, the increased miRNAs were verified by real-time PCR. Meanwhile, to ascertain the ability of some miRNAs to upregulate cleaved caspase 3 and induce GMC apoptosis, the corresponding miRNA mimics were transfected into GMCs, followed by western blotting (WB) and flow cytometry mesurement. Thereafter, the miR-3546-targeted gene (SOX4) was predicted using bioinformatics approaches, and SOX4 expression in Thy-1N tissues and in the GMCs upon sublytic C5b-9 stimulation or miR-3546 mimic/inhibitor transfection were detected using real-time PCR and WB. To prove that miR-3546 can affect SOX4 gene transcription and SOX4 can regulate survivin expression, dual luciferase reporter assay, real-time PCR, WB and chromatin immunoprecipitation (ChIP) assays were performed. Furthermore, the role of miR-3546/SOX4/survivin axis in the GMC apoptosis induced by sublytic C5b-9 was examined using WB and flow cytometry. Results: Compared with normal renal tissues and untreated GMCs, there were 43 and 62 upregulated miRNAs (> 2-fold) in Thy-1N tissues and sublytic C5b-9-stimulated GMCs respectively. A total of 17 miRNAs were increased both in vivo and in vitro, 11 of which were validated by real-time PCR. Among them, miR-3546 could markedly promote GMC apoptosis and inhibit SOX4 or survivin expression in response to sublytic C5b-9, and either SOX4 or survivin overexpression markedly rescued the GMC apoptosis mediated by miR-3546 mimic. Additionally, SOX4 overexpression could reverse the survivin suppression by miR-3546 mimic, and SOX4 could bind to survivin promoter (-1,278 to -853 nt) and activate survivin gene transcription. Conclusion: MiR-3546/ SOX4/survivin axis has a promoting role in the GMC apoptosis triggered by sublytic C5b-9, and our findings may provide a new insight into the pathogenesis of rat Thy-1N and human MsPGN

Morphological diversity of single neurons in molecularly defined cell types.

Dendritic and axonal morphology reflects the input and output of neurons and is a defining feature of neuronal types1,2, yet our knowledge of its diversity remains limited. Here, to systematically examine complete single-neuron morphologies on a brain-wide scale, we established a pipeline encompassing sparse labelling, whole-brain imaging, reconstruction, registration and analysis. We fully reconstructed 1,741 neurons from cortex, claustrum, thalamus, striatum and other brain regions in mice. We identified 11 major projection neuron types with distinct morphological features and corresponding transcriptomic identities. Extensive projectional diversity was found within each of these major types, on the basis of which some types were clustered into more refined subtypes. This diversity follows a set of generalizable principles that govern long-range axonal projections at different levels, including molecular correspondence, divergent or convergent projection, axon termination pattern, regional specificity, topography, and individual cell variability. Although clear concordance with transcriptomic profiles is evident at the level of major projection type, fine-grained morphological diversity often does not readily correlate with transcriptomic subtypes derived from unsupervised clustering, highlighting the need for single-cell cross-modality studies. Overall, our study demonstrates the crucial need for quantitative description of complete single-cell anatomy in cell-type classification, as single-cell morphological diversity reveals a plethora of ways in which different cell types and their individual members may contribute to the configuration and function of their respective circuits

Discovery of Novel 1,2,3-triazole Derivatives as IDO1 Inhibitors

Indoleamine 2,3-dioxygenase 1 (IDO1) has received much attention as an immunomodulatory enzyme in the field of cancer immunotherapy. While several IDO1 inhibitors have entered clinical trials, there are currently no IDO1 inhibitor drugs on the market. To explore potential IDO1 inhibitors, we designed a series of compounds with urea and 1,2,3-triazole structures. Organic synthesis and IDO1 enzymatic activity experiments verified the molecular-level activities of the designed compounds, and the IC50 value of compound 3a was 0.75 μM. Molecular docking and quantum mechanical studies further explained the binding mode and reaction potential of compound 3a with IDO1. Our research has resulted in a series of novel IDO1 inhibitors, which is beneficial to the development of drugs targeting IDO1 in numerous cancer diseases

Salt Content Distribution and Paleoclimatic Significance of the Lop Nur “Ear” Feature: Results from Analysis of EO-1 Hyperion Imagery

Lop Nur, a playa lake located on the eastern margin of Tarim Basin in northwestern China, is famous for the “Ear” feature of its salt crust, which appears in remote-sensing images. In this study, partial least squares (PLS) regression was used to estimated Lop Nur playa salt-crust properties, including total salt, Ca2+, Mg2+, Na+, Si2+, and Fe2+ using laboratory hyperspectral data. PLS results for laboratory-measured spectra were compared with those for resampled laboratory spectra with the same spectral resolution as Hyperion using the coefficient of determination (R2) and the ratio of standard deviation of sample chemical concentration to root mean squared error (RPD). Based on R2 and RPD, the results suggest that PLS can predict Ca2+ using Hyperion reflectance spectra. The Ca2+ distribution was compared to the “Ear area” shown in a Landsat Thematic Mapper (TM) 5 image. The mean value of reflectance from visible bands for a 14 km transversal profile to the “Ear area” rings was extracted with the TM 5 image. The reflectance was used to build a correlation with Ca2+ content estimated with PLS using Hyperion. Results show that the correlation between Ca2+ content and reflectance is in accordance with the evolution of the salt lake. Ca2+ content variation was consistent with salt deposition. Some areas show a negative correlation between Ca2+ content and reflectance, indicating that there could have been a small-scale temporary runoff event under an arid environmental background. Further work is needed to determine whether these areas of small-scale runoff are due to natural (climate events) or human factors (upstream channel changes)