Nuclear localization of orphan receptor protein kinase (Ror1) is mediated through the juxtamembrane domain

<p>Abstract</p> <p>Background</p> <p>Several receptor tyrosine kinases (RTKs) such as EGFR, FGFR, TRK, and VEGFR are capable of localizing in the cell nucleus in addition to their usual plasma membrane localization. Recent reports also demonstrate that nuclear-localized RTKs have important cellular functions such as transcriptional activation. On the basis of preliminary bioinformatic analysis, additional RTKs, including receptor tyrosine kinase-like orphan receptor 1 (Ror1) were predicted to have the potential for nuclear subcellular localization. Ror1 is a receptor protein tyrosine kinase that modulates neurite growth in the central nervous system. Because the nuclear localization capability of the Ror1 cytoplasmic domain has not been reported, we examined the cellular expression distribution of this region.</p> <p>Results</p> <p>The Ror1 cytoplasmic region was amplified and cloned into reporter constructs with fluorescent tags. Following transfection, the nuclear distribution patterns of transiently expressed fusion proteins were observed. Serial deletion constructs were then used to map the juxtamembrane domain of Ror1 (aa_471-513) for this nuclear translocation activity. Further site-directed mutagenesis suggested that a KxxK-16 aa-KxxK sequence at residues 486-509 is responsible for the nuclear translocation interaction. Subsequent immunofluorescence analysis by cotransfection of Ran and Ror1 implied that the nuclear translocation event of Ror1 might be mediated through the Ran pathway.</p> <p>Conclusions</p> <p>We have predicted several RTKs that contain the nuclear localization signals. This is the first report to suggest that the juxtamembrane domain of the Ror1 cytoplasmic region mediates the translocation event. Ran GTPase is also implicated in this event. Our study might be beneficial in future research to understand the Ror1 biological signaling pathway.</p

Applying the Resilience to the Community Development in Taiwan

In 1999, the Shishui community in Nantou County, Taiwan was severely damaged by the 921 earthquakes, with many houses collapsing and community facilities suffering unprecedented damage. In late 2001, a community development association was established, and with the efforts of residents, the community was awarded the title of Classic Rural Area by the government in 2007, becoming a nationally recognized leisure agriculture demonstration base. However, with the subsequent reduction of external resources, continuous loss of internal talents, and operational dysfunction of community organizations, the Shishui community eventually stagnated. How can we evaluate the community\u27s resilience in this situation? This study takes the Shishui community as its research field, integrates expert and scholar research on community resilience, constructs the elements of Shishui community development resilience through in-depth interviews with community residents, and analyzes Shishui community resilience indicators using the Fuzzy Delphi Method (FDM), with five main dimensions: sustainable development capacity, organizational leadership capacity, financial management capacity, community cohesion, and network resource capacity. Then, using the Similarity-based Importance-Performance Analysis (SBIPA) method, the study analyzes the evaluations of Shishui community residents on the satisfaction and importance of each resilience indicator. Finally, a total of 18 issues that residents consider important but have not yet reached the expected level of performance are identified, such as community resources and mechanisms to support young people returning to their hometowns and fair distribution of community resources by community organizations, which will become important directions for future community governance improvement

Deep ploughing localized services; expanding international horizons : Collaborative English Teaching Service-Learning Program between Minghsin University of Science and Technology and primary & junior high schools

On the basis of our experience in promoting localized service-learning programs over the past 6 years, our school, in collaboration with local primary and junior high schools, planned a Cooperative Service Learning Program with an emphasis on reflection and reciprocity in service learning. This Program was implemented in coordination with a Service-Learning Program (named Professional Ethics) initiated by the Department of Applied Foreign Languages of our school. In practice, college students are dispatched to primary and junior high schools to teach their students English and lead the primary and junior high school students to establish a campus English catchphrases environment. In the meantime, through structured reflective activities, this Program allows both college students and primary and junior high school students to benefit from service learning. The results of this Program include: 1) shared and handed over the experience and resources of colleges and universities in promoting service-learning to primary and junior high schools so as to push ahead the deep ploughing and sustainability of service learning in the local communities; 2) achieved the goal of mutual benefit between service providers and service receivers and assisted in improving the problem of lack of international education resources in remote villages in Hsinchu County so as to realize the spirit of social justice that is emphasized in the concept of service learning; 3) planned diversified and structured service-learning reflective activities for different target groups to allow both college students and primary & junior high school students to grow in actual service -learning experience in order to cultivate students’ awareness of social care and civic engagement and inspire students to agree with the concept of service learning so as to make a commitment to turn it into their personal value; 4) organized service-learning teacher training activities to cultivate service-learning seed teachers in primary and junior high schools so as to establish a localized service-learning network and build up a transformative service-learning partnership with local primary and junior high schools

Benchmarking of eight recurrent neural network variants for breath phase and adventitious sound detection on a self-developed open-access lung sound database-HF_Lung_V1

A reliable, remote, and continuous real-time respiratory sound monitor with automated respiratory sound analysis ability is urgently required in many clinical scenarios-such as in monitoring disease progression of coronavirus disease 2019-to replace conventional auscultation with a handheld stethoscope. However, a robust computerized respiratory sound analysis algorithm has not yet been validated in practical applications. In this study, we developed a lung sound database (HF_Lung_V1) comprising 9,765 audio files of lung sounds (duration of 15 s each), 34,095 inhalation labels, 18,349 exhalation labels, 13,883 continuous adventitious sound (CAS) labels (comprising 8,457 wheeze labels, 686 stridor labels, and 4,740 rhonchi labels), and 15,606 discontinuous adventitious sound labels (all crackles). We conducted benchmark tests for long short-term memory (LSTM), gated recurrent unit (GRU), bidirectional LSTM (BiLSTM), bidirectional GRU (BiGRU), convolutional neural network (CNN)-LSTM, CNN-GRU, CNN-BiLSTM, and CNN-BiGRU models for breath phase detection and adventitious sound detection. We also conducted a performance comparison between the LSTM-based and GRU-based models, between unidirectional and bidirectional models, and between models with and without a CNN. The results revealed that these models exhibited adequate performance in lung sound analysis. The GRU-based models outperformed, in terms of F1 scores and areas under the receiver operating characteristic curves, the LSTM-based models in most of the defined tasks. Furthermore, all bidirectional models outperformed their unidirectional counterparts. Finally, the addition of a CNN improved the accuracy of lung sound analysis, especially in the CAS detection tasks.Comment: 48 pages, 8 figures. To be submitte

Look, the World is Watching How We Treat Migrants! The Making of the Anti-Trafficking Legislation during the Ma Administration

Employing the spiral model, this research analyses how anti-human trafficking legislation was promulgated during the Ma Ying-jeou (Ma Yingjiu) presidency. This research found that the gov- ernment of Taiwan was just as accountable for the violation of mi- grants’ human rights as the exploitive placement agencies and abusive employers. This research argues that, given its reliance on the United States for political and security support, Taiwan has made great ef- forts to improve its human rights records and meet US standards for protecting human rights. The reform was a result of multilevel inputs, including US pressure and collaboration between transnational and domestic advocacy groups. A major contribution of this research is to challenge the belief that human rights protection is intrinsic to dem- ocracy. In the same light, this research also cautions against Taiwan’s subscription to US norms since the reform was achieved at the cost of stereotyping trafficking victimhood, legitimising state surveillance, and further marginalising sex workers

Assessing, quantifying and valuing the ecosystem services of coastal lagoons

The natural conservation of coastal lagoons is important not only for their ecological importance, but also because of the valuable ecosystem services they provide for human welfare and wellbeing. Coastal lagoons are shallow semi-enclosed systems that support important habitats such as wetlands, mangroves, salt-marshes and seagrass meadows, as well as a rich biodiversity. Coastal lagoons are also complex social-ecological systems with ecosystem services that provide livelihoods, wellbeing and welfare to humans. This study assessed, quantified and valued the ecosystem services of 32 coastal lagoons. The main findings of the study are: (i) the definitions of ecosystem services are still not generally accepted; (ii) the quantification of ecosystem services is made in many different ways, using different units; (iii) the evaluation in monetary terms of some ecosystem service is problematic, often relying on non-monetary evaluation methods; (iv) when ecosystem services are valued in monetary terms, this may represent very different human benefits; and, (v) different aspects of climate change, including increasing temperature, sea-level rise and changes in rainfall patterns threaten the valuable ecosystem services of coastal lagoons.DEVOTES project, from the European Union's Seventh Framework Programme for research, technological development and demonstration [308392]; networks and communities of Eurolag; Future Earth Coasts; SCOR; Fundacao para a Ciencia e a Tecnologia (FCT) Investigador Programme [IF/00331/2013]; Fundacao para a Ciencia e a Tecnologia [UID/MAR/04292/2013]; CESAM by FCT/MEC national funds (PIDDAC) [UID/AMB/50017/2013 - POCI-01-0145-FEDER-007638]; FEDER; European Commission, under the 7th Framework Programme through the collaborative research project LAGOONS [283157]; FCT [SFRH/BPD/107823/2015, SFRH/BPD/91494/2012