Telomerase flies the coop: the telomerase RNA component as a viral-encoded oncogene

Telomerase, the enzyme that elongates our telomeres, is crucial for cancer development based on extensive analyses of human cells, human cancers, and mouse models. New data now suggest that a viral telomerase RNA gene encoded by Marek's disease virus (MDV), an oncogenic herpesvirus of chickens, promotes tumor formation. These findings highlight the importance of telomerase in cancer and raise new questions regarding the mechanisms by which the telomerase RNA component supports tumorigenesis

Telomere Uncapping, Chromosomes, and Carcinomas

SummaryData from mouse models and from human cancers have supported the idea that telomere shortening leads to chromosomal instability and epithelial carcinogenesis. In this issue of Cancer Cell, Else et al. demonstrate that telomere uncapping—altering a protein that protects chromosome ends without shortening telomeres—also results in epithelial cancers

PENGUATAN DUKUNGAN SOSIAL TERHADAP KORBAN PEMERKOSAAN DI P2TP2A PEKANBARU PROVINSI RIAU

Permasalahan yang diteliti adalah upaya penguatan dukungan social terhadap korban pemerkosaan oleh P2TP2A Pekanbaru Provinsi Riau. Tujuan dari penelitian ini adalah untuk memahami sejauh mana penguatan dukungan sosial keluarga terhadap korban pemorkosaan di P2TP2A Pekanbaru Provinsi Riau. Metode penelitian yang digunakan adalah deskriptif kualitatif. Lokasi penelitian adalah tempat yang akan dijadikan subjek penelitian kali ini, yaitu di P2TP2A Pekanbaru Provinsi Riau. Sumber data primer dari hasil wawancara dan data sekunder jurnal dan buku. Key informan dalam penelitian ini adalah Kepala dan Pegawai P2TP2A. Hasil penelitian adalah Upaya penguatan sosial yang dilkukan P2TP2A dengan melakukan pembinaan terhadap korban perkosaan dengan langkah, pembinaan mental dan spiritual, pembinaan Sosial dan Psikologis serta pembinaan Kerampilan/kreatifita

Telomere length is a critical determinant for survival in multiple myeloma

The variable clinical outcomes of Multiple Myeloma (MM) patients are incompletely defined by current prognostication tools. We examined the clinical utility of high‐resolution telomere length analysis as a prognostic marker in MM. Cohort stratification, using a previously determined length threshold for telomere dysfunction, revealed that patients with short telomeres had a significantly shorter overall survival (P < 0·0001; HR = 3·4). Multivariate modelling using forward selection identified International Staging System (ISS) stage as the most important prognostic factor, followed by age and telomere length. Importantly, each ISS prognostic subset could be further risk‐stratified according to telomere length, supporting the inclusion of this parameter as a refinement of the ISS. Despite the introduction of novel therapeutic modalities, patients with multiple myeloma (MM) display a heterogeneous clinical course, with survival ranging from a few months to over 10 years. Therefore, there is a requirement for reliable prognostic and predictive markers in this disease to allow for risk stratification and rational clinical decision‐making. The most commonly used prognostic system in MM is the International Staging System (ISS) that is based on serum levels of both β2‐micoglobulin and albumin (Greipp et al, 2005). Recently the ISS has been improved upon by the inclusion of cytogenetic information to take into account the level of lactate dehydrogenase and the considerable genetic heterogeneity known to occur in this disease (Palumbo et al, 2015). Hyperdiploidy and the loss of whole chromosome arms is frequently detected in MM, which includes, amongst others, gains of 1q in 30% of cases and the loss of 17p in 7% of cases (Walker et al, 2010). Short dysfunctional telomeres are susceptible to DNA repair activities that can result in chromosomal fusion and the initiation of cycles of anaphase‐bridging, breakage and fusion that can drive genomic instability and clonal evolution (Artandi et al, 2000; Roger et al, 2013; Jones et al, 2014). Telomere dysfunction has been documented in numerous haematological malignancies (Jones et al, 2012), and is one putative mechanism that may lead to the genetic and clinical heterogeneity observed in MM (Wu et al, 2003) and may relate to changes in the 3D telomeric architecture that have been documented in MM cells (Klewes et al, 2013). Recently, we have shown that high‐resolution telomere analysis, combined with a functional definition of telomere length, can provide powerful prognostic information in several tumour types, including chronic lymphocytic leukaemia (CLL)(Lin et al, 2014), myelodysplasia (unpublished observations) and breast cancer (Simpson et al, 2015). Here we sought to apply these technologies to examine the prognostic utility of telomere length in MM

TERT Promotes Epithelial Proliferation through Transcriptional Control of a Myc- and Wnt-Related Developmental Program

Telomerase serves a critical role in stem cell function and tissue homeostasis. This role depends on its ability to synthesize telomere repeats in a manner dependent on the reverse transcriptase (RT) function of its protein component telomerase RT (TERT), as well as on a novel pathway whose mechanism is poorly understood. Here, we use a TERT mutant lacking RT function (TERTci) to study the mechanism of TERT action in mammalian skin, an ideal tissue for studying progenitor cell biology. We show that TERTci retains the full activities of wild-type TERT in enhancing keratinocyte proliferation in skin and in activating resting hair follicle stem cells, which triggers initiation of a new hair follicle growth phase and promotes hair synthesis. To understand the nature of this RT-independent function for TERT, we studied the genome-wide transcriptional response to acute changes in TERT levels in mouse skin. We find that TERT facilitates activation of progenitor cells in the skin and hair follicle by triggering a rapid change in gene expression that significantly overlaps the program controlling natural hair follicle cycling in wild-type mice. Statistical comparisons to other microarray gene sets using pattern-matching algorithms revealed that the TERT transcriptional response strongly resembles those mediated by Myc and Wnt, two proteins intimately associated with stem cell function and cancer. These data show that TERT controls tissue progenitor cells via transcriptional regulation of a developmental program converging on the Myc and Wnt pathways

PARTISIPASI MASYARAKAT DALAM OPEN GOVERNMENT PARTNERSHIP (OGP) DI PEMERINTAH KABUPATEN BOJONEGORO (STUDI KASUS DIALOG PUBLIK)

Abstrak Dinas Komunikasi dan Informatika Kabupaten Bojonegoro dalam kebijakan Open Government Partnership memiliki inovasi program dialog publik. Gambaran umum dialog publik yaitu diawali penjelasan seputar isu terkini yang disampaikan oleh OPD terkait, kemudian dilanjut dengan penyampaian ide gagasan maupun kritikan dari masyrakat. Program dialog publik terdapat masalah terkait partisipasi masyarakat menurun. Tujuan Penelitian untuk menggambarkan partisipasi Masyarakat dalam kebijakan Open Goverment Partnership (OGP) pada Dialog Publik di Pemerintah Kabupaten Bojonegoro.Jenis penelitian yang digunakan adalah penelitian deskriptif dengan pendekatan kualitatif. Sedangkan fokus penelitian yang terdiri dari partisipasi dalam pengambilan keputusan, partisipasi dalam pelaksanaan, Partisipasi dalam pengambilan manfaat, partisipasi dalam evaluasi. Teknik pengumpulan data yaitu teknik wawancara, observasi, dan dokumentasi yang dianalisis menggunakan teknik analisis data menurut Miles dan Huberman, antara lain pengumpulan data, reduksi data atau pengolahan data, penyajian data serta pemaparan dan penarikan kesimpulan. Hasil analisis tentang partisipasi dalam pengambilan keputusan masyarakat sebagai peserta dialog publik telah berpatisipasi secara langsung maupun tidak langsung dalam pengambilan keputusan dialog. Partisipasi dalam pelaksanaan masyarakat menyampaikan gagasan ide kritikan kepada Pemerintah Kabupaten Bojonegoro. Partisipasi masyarakat terhadap dialog publik selama ini mengalami naik turun karena ada beberapa faktor. Pertama dikarenakan cuaca tidak menentu seperti hujan deras yang menyebabkan masyarakat hanya mendengarkan lewat radio. Kedua, aspirasi sifatnya kelompok golongan atau individu. Biasanya kalau kelompok datangnya bersamaan contoh dari paguyuban parkir Desa Ledok, disabilitas Bojonegoro. Partisipasi dalam pengambilan manfaat pertama, masyarakat lebih berani menyampaikan gagasan, ide maupun kritikan kepada Pemerintah Kabupaten Bojonegoro. Kedua, ada keberanian Pemerintah menanggapi dengan baik dan cerdas. Ketiga, pemerintah bisa lebih mudah mendengar penyampaian gagasan ide maupun kritikan dari masyarakat. Partisipasi dalam evaluasi penyampaian evaluasi kepada masyarakat Dinas Kominfo dilaksanakan pada pertemuan Jumat berikutnya. Harapan disampaikan masyarakat berkali-kali siapapun yang akan melanjutkan pemimpin Kabupaten Bojonegoro agar tetap melanjutkan tradisi keterbukaan antara pejabat dengan rakyat melalui dialog publik. Adapun saran dari penelitian ini yaitu perlu adanya sosialisasi kembali terhadap pentingnya dialog publik terhadap masyarakat. Tanggapan ataupun jawaban yang diberikan oleh OPD terkait tindak lanjut pada dialog publik harus terdapat kepastian agar masyarakat yang memberikan gagasan, ide, maupun kritikan tidak disampaikan berulang-ulang pada pertemuan dialog publik yang mendatang. Kekhawatiran masyarakat terhadap dialog publik yaitu agar tetap diselenggarakan dan direncanakan, walaupun pada masa mendatang akan ada pergantian Bupati dan Wakil Bupati Kabupaten Bojonegoro Kata Kunci : Partisipasi masyarakat, Dialog publik Abstract Office of communications and Informatics in Bojonegoro Regency policy Open Government Partnership has a public dialog program innovation. An overview of the public dialogue that is preceded explanations regarding current issues presented by OPD are related, then dilanjut with the submission of the idea of the idea as well as criticism from people. The program of public dialog there is a problem regarding public participation is declining. Research objectives to describe the public participation in the policy of Open Government Partnership (OGP) on Public Dialogue in Bojonegoro regency Government.This type of research is descriptive research with qualitative approach. While the focus of the research consisted of participation in decision-making, participation in the implementation of, the participation in the taking of benefits, participation in the evaluation. Engineering data collection i.e., interview techniques, observation, and documentation that can be analyzed using techniques of data analysis according to Miles and Huberman, among others, data collection, data processing or data reduction, the presentation of data as well as exposure and the withdrawal of the conclusion.The results of the analysis of the participation in decision-making of the community as a participant in the public dialogue has participated directly or indirectly in the decision-making dialogue. Participation in the implementation of the community delivered the idea the idea of criticism to the Government District Bojonegoro. Public participation against public dialogue over this experience up and down because there are a number of factors. First because of the uncertain weather as heavy rain which caused the community just listen by radio. Second, the aspirations of the group or individual nature. Usually when a group coming of concurrent instances of associations Ledok Village parking, disability Bojonegoro. Participation in the taking of the first benefits, more daring society conveys ideas, ideas or criticism to the Government District Bojonegoro. Second, there is the courage of the Government responding with good and smart. Third, the Government can more easily hear submission idea ideas or criticism from the community. Participation in the evaluation of the submission Evaluation Service to the community at a meeting held Friday Kominfo next. Hope community delivered many times anyone that County leaders will continue the Bojonegoro still continue the tradition of openness between officials with the people through public dialogue. As for the suggestion of the study i.e. need for socializing back against the importance of the public dialogue on the community. Responses or answers given by OPD related follow-up on public dialogue must be certainty so that communities that give you an idea, ideas, criticism or not delivered over and over again at the next meeting of the public dialogue. Community concerns against the public dialogue that is to keep organized and planned, even if in the future there will be a changing of the Regent and Vice Regent Kabupaten Bojonegoro Keywords: public participation, public Dialogu

Proteostatic Control of Telomerase Function through TRiC-Mediated Folding of TCAB1

SummaryTelomere maintenance by telomerase is impaired in the stem cell disease dyskeratosis congenita and during human aging. Telomerase depends upon a complex pathway for enzyme assembly, localization in Cajal bodies, and association with telomeres. Here, we identify the chaperonin CCT/TRiC as a critical regulator of telomerase trafficking using a high-content genome-wide siRNA screen in human cells for factors required for Cajal body localization. We find that TRiC is required for folding the telomerase cofactor TCAB1, which controls trafficking of telomerase and small Cajal body RNAs (scaRNAs). Depletion of TRiC causes loss of TCAB1 protein, mislocalization of telomerase and scaRNAs to nucleoli, and failure of telomere elongation. DC patient-derived mutations in TCAB1 impair folding by TRiC, disrupting telomerase function and leading to severe disease. Our findings establish a critical role for TRiC-mediated protein folding in the telomerase pathway and link proteostasis, telomere maintenance, and human disease

Stem Cells and Aging:What's Next?

We asked 12 leaders in the stem cell and aging fields to share their personal perspectives on the future of the field and the unanswered questions that drive them to work in this exciting area