28 research outputs found

    Inhibition of the mitochondria-shaping protein Opa1 restores sensitivity to Gefitinib in a lung adenocarcinomaresistant cell line

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    Drug resistance limits the efficacy of chemotherapy and targeted cancer treatments, calling for the identification of druggable targets to overcome it. Here we show that the mitochondria-shaping protein Opa1 participates in resistance against the tyrosine kinase inhibitor gefitinib in a lung adenocarcinoma cell line. Respiratory profiling revealed that oxidative metabolism was increased in this gefitinib-resistant lung cancer cell line. Accordingly, resistant cells depended on mitochondrial ATP generation, and their mitochondria were elongated with narrower cristae. In the resistant cells, levels of Opa1 were increased and its genetic or pharmacological inhibition reverted the mitochondrial morphology changes and sensitized them to gefitinib-induced cytochrome c release and apoptosis. In vivo, the size of gefitinib-resistant lung orthotopic tumors was reduced when gefitinib was combined with the specific Opa1 inhibitor MYLS22. The combo gefitinib-MYLS22 treatment increased tumor apoptosis and reduced its proliferation. Thus, the mitochondrial protein Opa1 participates in gefitinib resistance and can be targeted to overcome it

    Enabling oxygen-controlled microfluidic cultures for spatiotemporal microbial single-cell analysis

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    Microfluidic cultivation devices that facilitate O2 control enable unique studies of the complex interplay between environmental O2 availability and microbial physiology at the single-cell level. Therefore, microbial single-cell analysis based on time-lapse microscopy is typically used to resolve microbial behavior at the single-cell level with spatiotemporal resolution. Time-lapse imaging then provides large image-data stacks that can be efficiently analyzed by deep learning analysis techniques, providing new insights into microbiology. This knowledge gain justifies the additional and often laborious microfluidic experiments. Obviously, the integration of on-chip O2 measurement and control during the already complex microfluidic cultivation, and the development of image analysis tools, can be a challenging endeavor. A comprehensive experimental approach to allow spatiotemporal single-cell analysis of living microorganisms under controlled O2 availability is presented here. To this end, a gas-permeable polydimethylsiloxane microfluidic cultivation chip and a low-cost 3D-printed mini-incubator were successfully used to control O2 availability inside microfluidic growth chambers during time-lapse microscopy. Dissolved O2 was monitored by imaging the fluorescence lifetime of the O2-sensitive dye RTDP using FLIM microscopy. The acquired image-data stacks from biological experiments containing phase contrast and fluorescence intensity data were analyzed using in-house developed and open-source image-analysis tools. The resulting oxygen concentration could be dynamically controlled between 0% and 100%. The system was experimentally tested by culturing and analyzing an E. coli strain expressing green fluorescent protein as an indirect intracellular oxygen indicator. The presented system allows for innovative microbiological research on microorganisms and microbial ecology with single-cell resolution

    Possible interpretations of the joint observations of UHECR arrival directions using data recorded at the Telescope Array and the Pierre Auger Observatory

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    Evidence from Natural and Field Experiments in a Developing Country

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    This study tests alternative hypotheses concerning the motivations behind the participation by rural households in community work. Using unique data from natural and field experiments in southern Sri Lanka, where irrigated fields have been allocated to farmers by government lottery, we compare quantitatively five possible motives behind community participation: public goods investment, general social capital accumulation, production network formation, risk sharing network formation, and pure altruism. Our empirical results show that community participation patterns are consistent with social capital accumulation behavior to form risk sharing networks. Only a few studies have investigated empirically the process of social capital formation, and our analysis fills the gap in the literature. Our findings also suggest the possibility of a poverty trap: facing negative shocks, poor households may have difficulty in finding time for social capital accumulation and risk sharing network formation; this, in turn, may cause them to become more vulnerable and even poorer

    ―Evidence from Sri Lanka―

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    This study uses a unique long panel dataset from Sri Lanka to examine the mechanism of social capital formation in an imperfect credit market. The authors show that households in the face of credit constraints reduce the time allocation for social capital investment, such as participation in community works. The paper also finds that temporal declines in social capital investment persistently reduce the level of trust in the community. These findings imply the existence of a poverty trap, because the absence of a credit market access generates poor social capital which, in turn, leads to poor access to the informal credit market, causing further credit constraints

    ―Evidence from Sri Lanka―

    No full text
    This study uses a unique long panel dataset from Sri Lanka to examine the mechanism of social capital formation in an imperfect credit market. The authors show that households in the face of credit constraints reduce the time allocation for social capital investment, such as participation in community works. The paper also finds that temporal declines in social capital investment persistently reduce the level of trust in the community. These findings imply the existence of a poverty trap, because the absence of a credit market access generates poor social capital which, in turn, leads to poor access to the informal credit market, causing further credit constraints
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