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| 2. |
- Carninci, P, et al.
(författare)
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The transcriptional landscape of the mammalian genome
- 2005
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Ingår i: Science (New York, N.Y.). - : American Association for the Advancement of Science (AAAS). - 1095-9203 .- 0036-8075. ; 309:5740, s. 1559-1563
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Tidskriftsartikel (refereegranskat)abstract
- This study describes comprehensive polling of transcription start and termination sites and analysis of previously unidentified full-length complementary DNAs derived from the mouse genome. We identify the 5′ and 3′ boundaries of 181,047 transcripts with extensive variation in transcripts arising from alternative promoter usage, splicing, and polyadenylation. There are 16,247 new mouse protein-coding transcripts, including 5154 encoding previously unidentified proteins. Genomic mapping of the transcriptome reveals transcriptional forests, with overlapping transcription on both strands, separated by deserts in which few transcripts are observed. The data provide a comprehensive platform for the comparative analysis of mammalian transcriptional regulation in differentiation and development.
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| 4. |
- Shrestha, R, et al.
(författare)
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Molecular pathogenesis of progression to myeloid leukemia from TET-insufficient status
- 2020
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Ingår i: Blood advances. - : American Society of Hematology. - 2473-9537 .- 2473-9529. ; 4:5, s. 845-854
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Tidskriftsartikel (refereegranskat)abstract
- Loss-of-function mutations in ten-eleven translocation-2 (TET2) are recurrent events in acute myeloid leukemia (AML) as well as in preleukemic hematopoietic stem cells (HSCs) of age-related clonal hematopoiesis. TET3 mutations are infrequent in AML, but the level of TET3 expression in HSCs has been found to decline with age. We examined the impact of gradual decrease of TET function in AML development by generating mice with Tet deficiency at various degrees. Tet2f/f and Tet3f/f mice were crossed with mice expressing Mx1-Cre to generate Tet2f/wtTet3f/fMx-Cre+ (T2ΔT3), Tet2f/fTet3f/wtMx-Cre+ (ΔT2T3), and Tet2f/fTet3f/fMx-Cre+ (ΔT2ΔT3) mice. All ΔT2ΔT3 mice died of aggressive AML at a median survival of 10.7 weeks. By comparison, T2ΔT3 and ΔT2T3 mice developed AML at longer latencies, with a median survival of ∼27 weeks. Remarkably, all 9 T2ΔT3 and 8 ΔT2T3 mice with AML showed inactivation of the remaining nontargeted Tet2 or Tet3 allele, respectively, owing to exonic loss in either gene or stop-gain mutations in Tet3. Recurrent mutations other than Tet3 were not noted in any mice by whole-exome sequencing. Spontaneous inactivation of residual Tet2 or Tet3 alleles is a recurrent genetic event during the development of AML with Tet insufficiency.
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| 5. |
- Iwama, R. E., et al.
(författare)
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Broad geographic sampling and DNA barcoding do not support the presence of Helobdella stagnalis (Linnaeus, 1758) (Clitellata: Glossiphoniidae) in North America
- 2019
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Ingår i: Zootaxa. - : Magnolia Press. - 1175-5326 .- 1175-5334. ; 4671:1, s. 1-25
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Tidskriftsartikel (refereegranskat)abstract
- The description of Helobdella stagnalis (Linnaeus, 1758) has emphasized the presence of a nuchal, chitinous scute located on the dorsal surface in the first third of the body as the diagnostic character for the species. Historically, identifications of species of Helobdella have relied heavily on this character and, as a result, Helobdella stagnalis has been reported from an inordinately broad geographic range, including Europe, Asia, Africa, North America, and South America. In addition to a few earlier investigations, a recent analysis showed that great genetic distances (orders of magnitude greater than previous estimations of intraspecific divergence in leeches) are present between scute-bearing specimens identified as H. stagnalis from Europe and North America, implying that H. stagnalis does not occur in North America. The present study expands the geographic boundaries of taxon sampling for both European and North American taxa, and re-examines the phylogenetic relationships and cytochrome c oxidase subunit I (COI) variation within scute-bearing species of the germs Helobdella. Our analyses include specimens putatively identified as "Helobdella stagnalis" from Sweden, Norway, Iceland, England, France, Italy, Slovenia, Turkey, Russia, and Iran, as well as numerous localities covering Canada and the USA. Our results corroborate previous studies in that European and west Asian specimens form a clade, including the neotype, which is separate from North American taxa. To alleviate future taxonomic confusion, we redescribe H. stagnalis and designate a neotype from the inferred type locality. The designation of a neotype stabilizes the taxonomy of scute bearing leeches of the genus Helobdella and enables us to definitively correct erroneous identifications reported in previous studies. We also note that at least four lineages of scute-bearing, North American species of Helobdella lack formal descriptions.
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| 6. |
- Björklund, Andreas, et al.
(författare)
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Spotting Trees with Few Leaves
- 2015
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Ingår i: Lecture Notes in Computer Science/Automata, Languages, and Programming. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783662476727 ; 9134, s. 243-255
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Konferensbidrag (refereegranskat)abstract
- We show two results related to the Hamiltonicity and k -Path algorithms in undirected graphs by Björklund [FOCS’10], and Björklund et al., [arXiv’10]. First, we demonstrate that the technique used can be generalized to finding some k-vertex tree with l leaves in an n-vertex undirected graph in O∗(1.657^k2^{l/2}) time. It can be applied as a subroutine to solve the k -Internal Spanning Tree (k-IST) problem in O∗(min(3.455^k,1.946^n)) time using polynomial space, improving upon previous algorithms for this problem. In particular, for the first time, we break the natural barrier of O∗(2^n). Second, we show that the iterated random bipartition employed by the algorithm can be improved whenever the host graph admits a vertex coloring with few colors; it can be an ordinary proper vertex coloring, a fractional vertex coloring, or a vector coloring. In effect, we show improved bounds for k-Path and Hamiltonicity in any graph of maximum degree Δ=4,…,12 or with vector chromatic number at most 8.
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| 7. |
- Iwama, K, et al.
(författare)
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Max-stretch reduction for tree spanners
- 2005
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Ingår i: Algorithms and Data Structures / Lecture Notes in Computer Science. - Berlin, Heidelberg : Springer Berlin Heidelberg. - 0302-9743 .- 1611-3349. - 9783540281016 ; 3608, s. 122-133
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Konferensbidrag (refereegranskat)abstract
- A tree t-spanner T of a graph G is a spanning tree of G whose max-stretch is t, i.e., the distance between any two vertices in T is at most t times their distance in G. If G has a tree t-spanner but not a tree (t - 1)-spanner, then G is said to have max-stretch of t. In this paper, we study the Max-Stretch Reduction Problem: for an unweighted graph G = (V, E), find a set of edges not in E originally whose insertion into G can decrease the max-stretch of G. Our results are as follows: (i) For a ring graph, we give a linear-time algorithm which inserts k edges improving the max-stretch optimally. (ii) For a grid graph, we give a nearly optimal max-stretch reduction algorithm which preserves the structure of the grid. (iii) In the general case, we show that it is NP-hard to decide, for a given graph G and its spanning tree of max-stretch t, whether or not one-edge insertion can decrease the max-stretch to t- 1. (iv) Finally, we show that the max-stretch of an arbitrary graph on n vertices can be reduced to s' >= 2 by inserting O(n/s') edges, which can be determined in linear time, and observe that this number of edges is optimal up to a constant.
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| 8. |
- Yamazaki, Satoshi, et al.
(författare)
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Nonmyelinating Schwann Cells Maintain Hematopoietic Stem Cell Hibernation in the Bone Marrow Niche
- 2011
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Ingår i: Cell. - : Elsevier BV. - 1097-4172 .- 0092-8674. ; 147:5, s. 1146-1158
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Tidskriftsartikel (refereegranskat)abstract
- Hematopoietic stem cells (HSCs) reside and self-renew in the bone marrow (BM) niche. Overall, the signaling that regulates stem cell dormancy in the HSC niche remains controversial. Here, we demonstrate that TGF-beta type II receptor-deficient HSCs show low-level Smad activation and impaired long-term repopulating activity, underlining the critical role of TGF-beta/Smad signaling in HSC maintenance. TGF-b is produced as a latent form by a variety of cells, so we searched for those that express activator molecules for latent TGF-beta. Nonmyelinating Schwann cells in BM proved responsible for activation. These glial cells ensheathed autonomic nerves, expressed HSC niche factor genes, and were in contact with a substantial proportion of HSCs. Autonomic nerve denervation reduced the number of these active TGF-beta-producing cells and led to rapid loss of HSCs from BM. We propose that glial cells are components of a BM niche and maintain HSC hibernation by regulating activation of latent TGF-beta.
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