The atypical Gaoligong orocline: Its geodynamic origin and evolution

Various orocline systems around the India–Eurasia collision zone have long been recognized and studied. Different portions of the India–Eurasia boundaries represent various scales and models of orocline-forming processes, such as the Baluchistan orocline formed by multiple deformation events and the Himalayan orocline formed by a mixture of complex structural mechanisms. The curvature from the eastern Himalayan syntaxis through east Burma to west Yunnan showed a unique convex curvature toward the mantle wedge. This is different from the concave Baluchistan orocline and the Himalayan orocline. The unique geometry of the Gaoligong orocline shows an N-S trend for the northern section and a NE-SW trend for the southern section. This curvature also marks the boundary between the Tengchong and Baoshan blocks along the Santaishan suture in western Yunnan, China. Our structural reconstruction identified five deformation events: 1) D1 is km-scale upright folding, which only affected the Neoproterozoic meta-sedimentary unit, 2) D2 recumbent folding, which only developed in the southern section of the Gaoligong orocline, 3) D3 large-scale gently westward-inclined thrust folding, 4) D4 right-lateral shear belt, and 5) the D5 normal faults. Since the D3 structure is the earliest event that shows penetrative foliation development along the orocline, we consider D1 and D2 as pre-orocline-forming events. The geometry of the Gaoligong orocline is controlled by the distribution of the Ordovician basement between the Tengchong and Baoshan blocks. Both north and south sections experienced the same structural evolution since D3 (a fault-propagation fold system occurred between 40 Ma and 28 Ma), D4 (steep right-lateral shear belt occurred between 28 Ma and 15 Ma), and D5 (normal faults after 15 Ma). The curvature first developed as a shovel-like top-to-the-NE thrust plane (S3) that formed under amphibolite-facies conditions between 40 Ma and 28 Ma. The following deformation events (D4 and D5) show orocline parallel foliation development under lower metamorphic conditions, indicating that the curvature of the Gaoligong orocline is not generated by additional rotation along multiple deformation events. However, due to the lack of orocline parallel foliation development for S3, and the lack of a proper position of the indenter, the Gaoligong orocline cannot be classified as a primary orocline nor a rotational orocline. The curved geometry is an interference pattern of topography relief to the shovel-like thrust plane that developed during D3. Our new reconstructed structural evolution concludes that the Gaoligong orocline is an “atypical” orocline

PARENTAGE OF OVERLAPPING OFFSPRING OF AN ARBOREAL-BREEDING FROG WITH NO NEST DEFENSE: IMPLICATIONS FOR NEST SITE SELECTION AND REPRODUCTIVE STRATEGY

Overlapping offspring occurs when eggs are laid in a nest containing offspring from earlier reproduction. To unveil the parentage between overlapping offspring and parents is critical in understanding oviposition site selection and the reproductive strategies of parents. Amplectant pairs of an arboreal-breeding frog, Kurixalus eiffingeri, lay eggs in tadpole-occupied nests where offspring of different life stages (embryos and tadpoles) coexist. We used five microsatellite DNA markers to assess the parentage between parents and overlapping offspring. Results showed varied parentage patterns, which may differ from the phenomenon of overlapping egg clutches reported earlier. Parentage analyses showed that only 58 and 25% of the tadpole-occupied stumps were reused by the same male and female respectively, partially confirming our prediction. Re-nesting by the same individual was more common in males than females, which is most likely related to the cost of tadpole feeding and/or feeding schemes of females. On the other hand, results of parentage analyses showed that about 42 and 75 % of male and female respectively bred in tadpole-occupied stumps where tadpoles were genetically unrelated. Results of a nest-choice experiment revealed that 40% of frogs chose tadpole-occupied bamboo cups when we presented identical stumps, without or with tadpoles, suggesting that the habitat saturation hypothesis does not fully explain why frogs used the tadpole-occupied stumps. Several possible benefits of overlapping offspring with different life stages were proposed. Our study highlights the importance of integrating molecular data with field observations to better understand the reproductive biology and nest site selection of anuran amphibians

PARENTAGE OF OVERLAPPING OFFSPRING OF AN ARBOREAL-BREEDING FROG WITH NO NEST DEFENSE: IMPLICATIONS FOR NEST SITE SELECTION AND REPRODUCTIVE STRATEGY

Overlapping offspring occurs when eggs are laid in a nest containing offspring from earlier reproduction. To unveil the parentage between overlapping offspring and parents is critical in understanding oviposition site selection and the reproductive strategies of parents. Amplectant pairs of an arboreal-breeding frog, Kurixalus eiffingeri, lay eggs in tadpole-occupied nests where offspring of different life stages (embryos and tadpoles) coexist. We used five microsatellite DNA markers to assess the parentage between parents and overlapping offspring. Results showed varied parentage patterns, which may differ from the phenomenon of overlapping egg clutches reported earlier. Parentage analyses showed that only 58 and 25% of the tadpole-occupied stumps were reused by the same male and female respectively, partially confirming our prediction. Re-nesting by the same individual was more common in males than females, which is most likely related to the cost of tadpole feeding and/or feeding schemes of females. On the other hand, results of parentage analyses showed that about 42 and 75 % of male and female respectively bred in tadpole-occupied stumps where tadpoles were genetically unrelated. Results of a nest-choice experiment revealed that 40% of frogs chose tadpole-occupied bamboo cups when we presented identical stumps, without or with tadpoles, suggesting that the habitat saturation hypothesis does not fully explain why frogs used the tadpole-occupied stumps. Several possible benefits of overlapping offspring with different life stages were proposed. Our study highlights the importance of integrating molecular data with field observations to better understand the reproductive biology and nest site selection of anuran amphibians

The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance

Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.published_or_final_versio

Phase 1 study of capmatinib in MET-positive solid tumor patients: Dose escalation and expansion of selected cohorts

Capmatinib is an oral, ATP-competitive, and highly potent, type 1b MET inhibitor. Herein, we report phase 1 dose-escalation results for capmatinib in advanced METpositive solid tumor patients and dose expansion in advanced non-lung tumors. Capmatinib was well tolerated with a manageable safety profile across all explored doses. Dose-limiting toxicities (DLT) occurred at 200 mg twice daily (bid), 250 mg bid, and 450 mg bid capsules; however, no DLT were reported at 600 mg bid (capsules). Capmatinib tablets at 400 mg bid had comparable tolerability and exposure to that of 600 mg bid capsules. Maximum tolerated dose was not reached; recommended phase 2 dose was 400 mg bid tablets/600 mg bid capsules; at this dose, C-trough >EC90 (90% inhibition of c-MET phosphorylation in animal models) is expected to be achieved and maintained. Among the dose-expansion patients (N = 38), best overall response across all cohorts was stable disease (gastric cancer 22%, hepatocellular carcinoma 46%, other indications 28%); two other indication patients with gene copy number (GCN) >= 6 achieved substantial tumor reduction. Near-complete immunohistochemically determined phospho-MET inhibition (H-score = 2) was shown following capmatinib 450 mg bid capsule in paired biopsies obtained from one advanced colorectal cancer patient. Incidence of high-level MET GCN (GCN >= 6) and MET-overexpressing (immunohistochemistry 3+) tumors in the expansion cohorts was 8% and 13%, respectively; no MET mutations were observed. Thus, the recommended phase 2 dose (RP2D) of capmatinib was 600 mg bid capsule/400 mg bid tablet. Capmatinib was well tolerated and showed antitumor activity and acceptable safety profile at the (ClinicalTrials.gov Identifier: NCT01324479).

Honokiol Eliminates Human Oral Cancer Stem-Like Cells Accompanied with Suppression of Wnt/ β

Honokiol, an active compound of Magnolia officinalis, exerted many anticancer effects on various types of cancer cells. We explored its effects on the elimination of cancer stem-like side population (SP) cells in human oral squamous cell carcinoma SAS cells. The sorted SP cells possessed much higher expression of stemness genes, such as ABCG2, ABCC5, EpCAM, OCT-4, CD133, CD44, and β-catenin, and more clonogenicity as compared with the Non-SP cells. After 48 h of treatment, honokiol dose dependently reduced the proportion of SP from 2.53% to 0.09%. Apoptosis of honokiol-treated SP cells was evidenced by increased annexin V staining and cleaved caspase-3 as well as decreased Survivin and Bcl-2. Mechanistically, honokiol inhibited the CD44 and Wnt/β-catenin signaling of SP cells. The Wnt signaling transducers such as β-catenin and TCF-4 were decreased in honokiol-treated SP cells, while the β-catenin degradation promoting kinase GSK-3α/β was increased. Consistently, the protein levels of β-catenin downstream targets such as c-Myc and Cyclin D1 were also downregulated. Furthermore, the β-catenin-related EMT markers such as Slug and Snail were markedly suppressed by honokiol. Our findings indicate honokiol may be able to eliminate oral cancer stem cells through apoptosis induction, suppression of Wnt/β-catenin signaling, and inhibition of EMT

Associations of Problematic Internet Use, Weight-Related Self-Stigma, and Nomophobia with Physical Activity: Findings from Mainland China, Taiwan, and Malaysia

Insufficient physical activity is a common problem for university students because they may engage in sedentary lifestyle owing to excessive time spent on their smartphones and social media use. This may result in problematic internet use (PIU) and nomophobia (fear of not having a mobile phone). Moreover, prior evidence shows that weight-related self-stigma is an important factor contributing to low physical activity. Therefore, the present study examined the associations between PIU, nomophobia, and physical activity among university students across mainland China, Taiwan, and Malaysia. Participants (3135 mainland Chinese, 600 Taiwanese, and 622 Malaysian) completed the Bergen Social Media Addiction Scale (BSMAS), Smartphone Application-Based Addiction Scale (SABAS), Nomophobia Questionnaire (NMPQ), Weight Self-Stigma Questionnaire (WSSQ), and International Physical Activity Questionnaire Short Form (IPAQ-SF). The measurement invariance of the assessed questionnaires was supported across the three regions. The present findings analyzed using partial least squares structural equation modeling showed that (i) greater nomophobia was associated with higher levels of physical activity, (ii) greater weight-related self-stigma was associated with higher levels of physical activity, and (iii) greater nomophobia was associated with greater weight-related self-stigma. Although the present findings suggest the possibility that experiencing some level of nomophobia or weight-related self-stigma appears to help improve physical activity, it is not recommended that these be encouraged, but reducing PIU should be targeted as a means to improve physical activit

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data