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| 2. |
- Rossi, Derrick J, et al.
(författare)
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Cell intrinsic alterations underlie hematopoietic stem cell aging
- 2005
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 102:26, s. 9194-9199
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Tidskriftsartikel (refereegranskat)abstract
- Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid specification and function and up-regulation of genes involved in specifying myeloid fate and function. Moreover, LT-HSCs from old mice expressed elevated levels of many genes involved in leukemic transformation. These data support a model in which age-dependent alterations in gene expression at the stem cell level presage downstream developmental potential and thereby contribute to age-dependent immune decline, and perhaps also to the increased incidence of leukemia in the elderly.
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| 3. |
- Brose, Ulrich, et al.
(författare)
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Body sizes of consumers and their resources
- 2005
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Ingår i: Ecology. - : Ecological Society of America. - 0012-9658 .- 1939-9170. ; 86:9, s. 2545-2545
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Tidskriftsartikel (refereegranskat)abstract
- Trophic information—who eats whom—and species’ body sizes are two of the most basic descriptions necessary to understand community structure as well as ecological and evolutionary dynamics. Consumer–resource body size ratios between predators and their prey, and parasitoids and their hosts, have recently gained increasing attention due to their important implications for species’ interaction strengths and dynamical population stability. This data set documents body sizes of consumers and their resources. We gathered body size data for the food webs of Skipwith Pond, a parasitoid community of grass-feeding chalcid wasps in British grasslands; the pelagic community of the Benguela system, a source web based on broom in the United Kingdom; Broadstone Stream, UK; the Grand Caric¸aie marsh at Lake Neuchaˆtel, Switzerland; Tuesday Lake, USA; alpine lakes in the Sierra Nevada of California; Mill Stream, UK; and the eastern Weddell Sea Shelf, Antarctica. Further consumer–resource body size data are included for planktonic predators, predatory nematodes, parasitoids, marine fish predators, freshwater invertebrates, Australian terrestrial consumers, and aphid parasitoids. Containing 16 807 records, this is the largest data set ever compiled for body sizes of consumers and their resources. In addition to body sizes, the data set includes information on consumer and resource taxonomy, the geographic location of the study, the habitat studied, the type of the feeding interaction (e.g., predacious, parasitic) and the metabolic categories of the species (e.g., invertebrate, ectotherm vertebrate). The present data set was gathered with the intent to stimulate research on effects of consumer–resource body size patterns on food-web structure, interaction-strength distributions, population dynamics, and community stability. The use of a common data set may facilitate cross-study comparisons and understanding of the relationships between different scientific approaches and models.
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| 4. |
- Sandalova, T., et al.
(författare)
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A structural basis for CD8(+) T cell-dependent recognition of non-homologous peptide ligands - Implications for molecular mimicry in autoreactivity
- 2005
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Ingår i: Journal of Biological Chemistry. - 0021-9258 .- 1083-351X. ; 280:29, s. 27069-27075
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Tidskriftsartikel (refereegranskat)abstract
- Molecular mimicry of self-epitopes by viral antigens is one possible pathogenic mechanism underlying induction of autoimmunity. A self-epitope, mDBM, derived from mouse dopamine beta-mono-oxygenase (KALYDYAPI) sharing 44% sequence identity with the lymphocytic choriomeningitis virus-derived immunodominant epitope gp33 (KAVYNFATC/ M), has previously been identified as a cross-reactive self-ligand, presentation of which results in autoimmunity. A rat peptide homologue, rDBM (KALYNYAPI, 56% identity to gp33), which displayed similar properties to mDBM, has also been identified. We herein report the crystal structure of H-2D(b)center dot rDBM and a comparison with the crystal structures of the cross-reactive H-2D(b)center dot gp33 and non- cross- reactive H-2D(b)center dot gp33 (V3L) escape variant (KALYNFATM, 88% identity to gp33). Despite the large sequence disparity, rDBM and gp33 peptides are presented in nearly identical manners by H-2D(b), with a striking juxtaposition of the central sections of both peptides from residues p3 to p7. The structural similarity provides H-2D(b) in complex with either a virus-derived or a dopamine beta-mono-oxygenase-derived peptide with a shared antigenic identity that conserves the positioning of the heavy chain and peptide residues that interact with the T cell receptor (TCR). This stands in contrast to the structure of H-2D(b) center dot gp33 (V3L), in which a single conserved mutation, also present in rDBM, induces large movements of both the peptide backbone and the side chains that interact with the TCR. The TCR-interacting surfaces of the H-2D(b) center dot rDBM and H-2D(b) center dot gp33 major histocompatibility complexes are very similar with regard to shape, topology, and charge distribution, providing a structural basis for CD8 T cell activation by molecular mimicry and potential subsequent development of autoreactivity.
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| 5. |
- Sosnoff, Jacob J., et al.
(författare)
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Coherence of EMG activity and single motor unit discharge patterns in human rhythmical force production.
- 2005
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Ingår i: Behavioural Brain Research. - : Elsevier BV. - 0166-4328 .- 1872-7549. ; 158:2, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- The purpose of this study was to examine the modulation of the motor neuronal pool as a function of task dynamics. Specifically, we investigated the effects of task frequency on the single motor unit discharge pattern, electromyogram (EMG) activity and effector force output. Myoelectric activity and effector force were recorded while young adults isometrically abducted their first dorsal interosseus at five sinusoidal targets (0.5 Hz, 1 Hz, 2 Hz, 3Hz and 4 Hz) and at two force levels (5% and 25% maximum voluntary contraction (MVC)). Individual motor unit spike trains were isolated from the EMG. Auto-spectral and coherence analyses were performed on the force output, EMG and motor unit spike trains. The frequency of maximal coherence between the EMG and force output closely corresponded to the target frequency in all conditions. There was a broadband distribution of power with multiple peaks in the EMG and motor unit spectrums in the 0.5 Hz and 1Hz targets. However, the EMG and motor unit spectrums in the 2 Hz, 3Hz and 4Hz targets were characterized by an increasingly narrower band of activity with one dominant peak that closely corresponded to the target. There is high coherence between EMG output and target force frequency, but the relative contribution of the fast and slow neuromuscular bands are differentially influenced by the task frequency. The rhythmical organization of neuromuscular output in the 0.5 Hz task is relatively broadband and similar to that shown previously for constant level force output. The frequency structure of neuromuscular organization becomes increasingly more narrowband as the frequency of the target increases (2–4 Hz). The modulation of the motor neuronal pool is adaptive and depends on the relative contribution of feedback and feedforward control processes, which are driven by the task demands.
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