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81.
Stem cells exhibit promise in numerous areas of regenerative medicine. Their fate and function are governed by a combination of intrinsic determinants and signals from the local microenvironment, or niche. An understanding of the mechanisms underlying both embryonic and adult stem cell functions has been greatly enhanced by the recent development of several high-throughput technologies: microfabricated platforms, including cellular microarrays, to investigate the combinatorial effects of microenvironmental stimuli and large-scale screens utilizing small molecules and short interfering RNAs to identify crucial genetic and signaling elements. Furthermore, the integration of these systems with other versatile platforms, such as microfluidics and lentiviral microarrays, will continue to enable the detailed elucidation of stem cell processes, and thus, greatly contribute to the development of stem cell based therapies. 相似文献
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David Gresham Bharti Morar Peter A. Underhill Giuseppe Passarino Alice A. Lin Cheryl Wise Dora Angelicheva Francesc Calafell Peter J. Oefner Peidong Shen Ivailo Tournev Rosario de?Pablo Vaidutis Ku?inskas Anna Perez-Lezaun Elena Marushiakova Vesselin Popov Luba Kalaydjieva 《American journal of human genetics》2001,69(6):1314-1331
The identification of a growing number of novel Mendelian disorders and private mutations in the Roma (Gypsies) points to their unique genetic heritage. Linguistic evidence suggests that they are of diverse Indian origins. Their social structure within Europe resembles that of the jatis of India, where the endogamous group, often defined by profession, is the primary unit. Genetic studies have reported dramatic differences in the frequencies of mutations and neutral polymorphisms in different Romani populations. However, these studies have not resolved ambiguities regarding the origins and relatedness of Romani populations. In this study, we examine the genetic structure of 14 well-defined Romani populations. Y-chromosome and mtDNA markers of different mutability were analyzed in a total of 275 individuals. Asian Y-chromosome haplogroup VI-68, defined by a mutation at the M82 locus, was present in all 14 populations and accounted for 44.8% of Romani Y chromosomes. Asian mtDNA-haplogroup M was also identified in all Romani populations and accounted for 26.5% of female lineages in the sample. Limited diversity within these two haplogroups, measured by the variation at eight short-tandem-repeat loci for the Y chromosome, and sequencing of the HVS1 for the mtDNA are consistent with a small group of founders splitting from a single ethnic population in the Indian subcontinent. Principal-components analysis and analysis of molecular variance indicate that genetic structure in extant endogamous Romani populations has been shaped by genetic drift and differential admixture and correlates with the migrational history of the Roma in Europe. By contrast, social organization and professional group divisions appear to be the product of a more recent restitution of the caste system of India. 相似文献
84.
Ron W. Summers Les G. Underhill Mike Nicoll Karl-Birger Strann & Stein Ø. Nilsen 《Ibis》2004,146(3):394-403
Timing and duration of primary moult in three populations of Purple Sandpipers Calidris maritima were described and discussed in relation to the birds’ need to complete moult before the onset of winter, when resources are required for survival. We predicted that moult would be completed earlier by birds wintering at higher latitudes. The south Norwegian breeding population, which moults and winters along the coast of east Britain (54–57°N) had a mean starting date of 21 July for primary moult (16 July for females and 24 July for males), a mean duration of 61 days, and completed on 20 September. Resident Icelandic (64–65°N) birds had a mean starting date of 22 July for primary moult (17 July for females and 25 July for males), a mean duration of 51 days, and completed on 11 September. Birds moulting in north Norway (70°N) arrived in north Norway in suspended primary moult or without having started moult, and completed it there. They had a mean completion date of 2 November for primary moult (31 October for females and 3 November for males). Starting date and duration could not be estimated because some suspended moult for an undetermined period, but it was thought that they started in late August. It is likely that most originated from Russia. The onset of moult appears to be set by the end of breeding and there is little overlap in these two events. The earlier start of moult by females in all three populations may be because they abandon the males when the chicks hatch, leaving the males to attend the chicks. Although the duration of primary moult followed the expected trend, being fastest in north Norway and slowest in Britain, the onset of moult was so late in north Norway that they had an unexpectedly late completion date, despite their rapid moult. The late completion of primary moult in north Norway suggests that wintering in the far north may not pose the energetic constraints on Purple Sandpipers that had previously been supposed. 相似文献
85.
Adam J Carlton JingYi Jeng Fiorella C Grandi Francesca De Faveri Federico Ceriani Lara De Tomasi Anna Underhill Stuart L Johnson Kevin P Legan Corn J Kros Guy P Richardson Mirna Mustapha Walter Marcotti 《The EMBO journal》2023,42(4)
Sensory‐independent Ca2+ spiking regulates the development of mammalian sensory systems. In the immature cochlea, inner hair cells (IHCs) fire spontaneous Ca2+ action potentials (APs) that are generated either intrinsically or by intercellular Ca2+ waves in the nonsensory cells. The extent to which either or both of these Ca2+ signalling mechansims are required for IHC maturation is unknown. We find that intrinsic Ca2+ APs in IHCs, but not those elicited by Ca2+ waves, regulate the maturation and maintenance of the stereociliary hair bundles. Using a mouse model in which the potassium channel Kir2.1 is reversibly overexpressed in IHCs (Kir2.1‐OE), we find that IHC membrane hyperpolarization prevents IHCs from generating intrinsic Ca2+ APs but not APs induced by Ca2+ waves. Absence of intrinsic Ca2+ APs leads to the loss of mechanoelectrical transduction in IHCs prior to hearing onset due to progressive loss or fusion of stereocilia. RNA‐sequencing data show that pathways involved in morphogenesis, actin filament‐based processes, and Rho‐GTPase signaling are upregulated in Kir2.1‐OE mice. By manipulating in vivo expression of Kir2.1 channels, we identify a “critical time period” during which intrinsic Ca2+ APs in IHCs regulate hair‐bundle function. 相似文献
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Ebert O Wilbert D Buttgereit P Ziske C Flieger D Schmidt-Wolf IG 《Genetic vaccines and therapy》2004,2(1):15
Background
Modulation of the immune system by genetically modified lymphoma cell vaccines is of potential therapeutic value in the treatment of B cell lymphoma. However, the anti-tumor effect of any single immunogene transfer has so far been limited. Combination treatment of recombinant IL-2 and IL-12 has been reported to be synergistic for inducing anti-tumor responses in solid tumors but the potential of IL-2/IL-12 gene modified B cell lymphoma cells has not been explored yet. 相似文献89.
R. A. Navarro H. A. J. Meijer L. G. Underhill 《Marine and Freshwater Behaviour and Physiology》2018,51(1):30-43
Cape gannet Morus capensis chicks depend entirely on fish prey and metabolic water for water requirements during development. Water loss through evaporative cooling due to heat stress is substantial. We measured water flux and field metabolic rates (FMR) of Cape gannet chicks and adults to determine if gannets developed water saving strategies. The water economy index (WEI, g kJ?1) decreased with chick age according to the model WEI = 0.676 – 0.272 × log10(t), indicating that water efficiency increased with age. At fledging, the WEI of chicks was at the level expected of adult desert birds. Desert birds maintain a low WEI by also having a low FMR, whereas Cape gannet chicks have FMR comparable to other seabird species’ nestling requirements. We propose that maintaining low WEI is adaptive for Cape gannets because (1) chicks need to balance water loss through evaporative cooling, (2) fledglings need to overcome a period of up to a week when they cannot ingest any water and (3) adults spend extended periods in the breeding colony during which water can become a limiting factor. Understanding the physiological mechanism of maintaining low WEI will become increasingly important with future rising temperatures. 相似文献
90.
Thomas GH; Newbern EC; Korte CC; Bales MA; Muse SV; Clark AG; Kiehart DP 《Molecular biology and evolution》1997,14(12):1285-1295
Many structural, signaling, and adhesion molecules contain tandemly
repeated amino acid motifs. The alpha-actinin/spectrin/dystrophin
superfamily of F-actin-crosslinking proteins contains an array of triple
alpha-helical motifs (spectrin repeats). We present here the complete
sequence of the novel beta-spectrin isoform beta(Heavy)- spectrin (beta H).
The sequence of beta H supports the origin of alpha- and beta-spectrins
from a common ancestor, and we present a novel model for the origin of the
spectrins from a homodimeric actin-crosslinking precursor. The pattern of
similarity between the spectrin repeat units indicates that they have
evolved by a series of nested, nonuniform duplications. Furthermore, the
spectrins and dystrophins clearly have common ancestry, yet the repeat unit
is of a different length in each family. Together, these observations
suggest a dynamic period of increase in repeat number accompanied by
homogenization within each array by concerted evolution. However, today,
there is greater similarity of homologous repeats between species than
there is across repeats within species, suggesting that concerted evolution
ceased some time before the arthropod/vertebrate split. We propose a
two-phase model for the evolution of the spectrin repeat arrays in which an
initial phase of concerted evolution is subsequently retarded as each new
protein becomes constrained to a specific length and the repeats diverge at
the DNA level. This evolutionary model has general applicability to the
origins of the many other proteins that have tandemly repeated motifs.
相似文献