Name and Subject Heading Reconciliation to Linked Open Data Authorities using Virtual International Authority File and Library of Congress Linked Data Service APIs: A Case Study featuring Emblematica Online

Libraries are actively exploring ways to use Linked Open Data (LOD) services to enhance discovery and facilitate the use of collections. Emblematica Online, which provides integrated discovery of digitized emblem books, incorporates LOD in its design. As an implementation prerequisite, the Virtual International Authority File (VIAF) and Library of Congress (LC) Linked Data Service APIs were used to reconcile name and subject strings from legacy catalog records with global authoritative links from LOD resources. This case study reports on the automated reconciliation process used and examines the efficacy of the APIs in reconciling name and subject heading entities. While a majority of strings were successfully reconciled, analysis suggests that data cleanup, rigorously consistent formatting of metadata strings, and addressing challenges in existing LOD resources and services could improve results for this corpus

Knockdown of Brm and Baf170, Components of Chromatin Remodeling Complex, Facilitates Reprogramming of Somatic Cells

© Copyright 2015, Mary Ann Liebert, Inc. 2015. The SWI/SNF (SWItch/Sucrose NonFermentable or BAF, Brg/Brahma-associated factors) complexes are epigenetic modifiers of chromatin structure and undergo progressive changes in subunit composition during cellular differentiation. For example, in embryonic stem cells, esBAF contains Brg1 and Baf155, while their homologs, Brm and Baf170, are present in BAF of somatic cells. In this study, we sought to determine whether Brm and Baf170 play any roles in induced pluripotent stem cell (iPSC) reprogramming by using shRNA-mediated knockdown studies in the mouse model. We found that knocking down Brm during early, mid, and late stages (days 3, 6, and 9 after initial iPSC induction) and knocking down Baf170 during late-stage (day 9) reprogramming improve the numbers of iPSC colonies formed. We further showed that inhibition of these somatic BAF components also promotes complete reprogramming of partially reprogrammed somatic cells (pre-iPSCs). Finally, we found that the expression of Brm and Baf170 during reprogramming was regulated by Jak/Stat3 activity. Taken together, these data suggest that inhibiting somatic BAF improves complete reprogramming by facilitating the activation of the pluripotency circuitry

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Name and Subject Heading Reconciliation to Linked Open Data Authorities using Virtual International Authority File and Library of Congress Linked Data Service APIs: A Case Study featuring Emblematica Online

Libraries are actively exploring ways to use Linked Open Data (LOD) services to enhance discovery and facilitate the use of collections. Emblematica Online, which provides integrated discovery of digitized emblem books, incorporates LOD in its design. As an implementation prerequisite, the Virtual International Authority File (VIAF) and Library of Congress (LC) Linked Data Service APIs were used to reconcile name and subject strings from legacy catalog records with global authoritative links from LOD resources. This case study reports on the automated reconciliation process used and examines the efficacy of the APIs in reconciling name and subject heading entities. While a majority of strings were successfully reconciled, analysis suggests that data cleanup, rigorously consistent formatting of metadata strings, and addressing challenges in existing LOD resources and services could improve results for this corpus

Differential effects of Akt isoforms on somatic cell reprogramming

© 2014. Akt plays an important role in cell growth, proliferation and survival. The specific roles of the three Akt isoforms in somatic cell reprogramming have not been investigated. Here we report that, during iPSC generation, enhanced Akt1 activity promotes complete reprogramming mainly through increased activation of Stat3 in concert with leukemia inhibitory factor (LIF) and, to a lesser extent, through promotion of colony formation. Akt1 augments Stat3 activity through activation of mTOR and upregulation of LIF receptor expression. Similarly, enhanced Akt2 or Akt3 activation also promotes reprogramming and coordinates with LIF to activate Stat3. Blocking Akt1 or Akt3 but not Akt2 expression prohibits cell proliferation and reprogramming. Furthermore, the halt in cell proliferation and reprogramming caused by mTOR and Akt inhibitors can be reversed by inhibition of GSK3. Finally, we found that expressing the GSK3b target Esrrb overrides inhibition of Akt and restores reprogramming. Our data demonstrated that during reprogramming, Akt promotes establishment of pluripotency through co-stimulation of Stat3 activity with LIF. Akt1 and Akt3 are essential for the proliferation of reprogrammed cells, and Esrrb supports cell proliferation and complete reprogramming during Akt signaling

LIF-activated Jak signaling determines Esrrb expression during late-stage reprogramming

The regulatory process of naïve-state induced pluripotent stem cell (iPSC) generation is not well understood. Leukemia inhibitory factor (LIF)-activated Janus kinase/signal transducer and activator of transcription 3 (Jak/Stat3) is the master regulator for naïve-state pluripotency achievement and maintenance. The estrogen-related receptor beta (Esrrb) serves as a naïve-state marker gene regulating self-renewal of embryonic stem cells (ESCs). However, the interconnection between Esrrb and LIF signaling for pluripotency establishment in reprogramming is unclear. We screened the marker genes critical for complete reprogramming during mouse iPSC generation, and identified genes including Esrrb that are responsive to LIF/Jak pathway signaling. Overexpression of Esrrb resumes the reprogramming halted by inhibition of Jak activity in partially reprogrammed cells (pre-iPSCs), and leads to the generation of pluripotent iPSCs. We further show that neither overexpression of Nanog nor stimulation of Wnt signaling, two upstream regulators of Esrrb in ESCs, stimulates the expression of Esrrb in reprogramming when LIF or Jak activity is blocked. Our study demonstrates that Esrrb is a specific reprogramming factor regulated downstream of the LIF/Jak signaling pathway. These results shed new light on the regulatory role of LIF pathway on complete pluripotency establishment during iPSC generation