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S Lowell

Publications and source records attributed to S Lowell.

11 recordsLinked to original sources
PubMed2005

Isolation by distance and a chromosomal cline in the Cayapa cytospecies of Simulium exiguum, the vector of human onchocerciasis in Ecuador.

The population genetic structure of the Cayapa cytospecies of Simulium exiguum, the vector of onchocerciasis, was analysed using allozyme frequency and chromosomal inversion polymorphism data from 6 and 15 populations respectively, collected in Ecuador. Eight allozyme loci were scored. No unique allozyme markers were found enabling us to identify biting adults of the vector from the non-vector Bucay cytotype. Mannose-phosphate isomerase (Mpi) contributed largely to the significant heterogeneity in gene frequency among populations of the Cayapa cytospecies and also to the overall population structuring (F(ST) = 0.015 +/- 0.014) which fitted the isolation by distance model. However, heterozygote deficits were recorded for Mpi in four of the six populations, which could indicate that selection is acting at this locus but this hypothesis will require further convincing evidence. Furthermore the significant population structuring of allozymes was not evident when Mpi was omitted from the analysis. All inversion polymorphisms (IIS-B, IIS-F, IIL-A and IIL-B) were in Hardy-Weinberg equilibrium, showed significant heterogeneity between populations and revealed the occurrence of an altitudinal cline in inversion IIS-B frequency. The inversion polymorphisms revealed a significant degree of population structuring (F(ST) = 0.083 +/- 0.027), which can be explained by the isolation by distance model. A UPGMA cluster analysis revealed the relatively remote, high altitude Rio Mira populations to be the most genetically distinct.

Animals↗
PubMed2001

Delta regulates keratinocyte spreading and motility independently of differentiation.

In human interfollicular epidermis stem cells lie in clusters surrounded by their differentiated daughters, transit amplifying cells, an arrangement that reflects differences in cell cohesiveness and motility. Keratinocytes expressing a dominant negative Delta1 mutant, Delta(T), lacking most of the cytoplasmic domain, acquired the motile behaviour of transit cells while retaining their stem cell identity. Conversely, overexpression of Delta1 promoted keratinocyte cohesiveness. The adhesive effects of Delta1 and Delta(T) were independent of SuH-dependent Notch signalling. Delta(T) increased motility and spreading of individual keratinocytes and stimulated lamellipodia formation. Delta and Delta(T) colocalised with cortical actin and redistributed on Latrunculin treatment. We propose that Delta promotes keratinocyte cohesiveness by restricting motility and discuss potential mechanisms by which Delta could interact with the actin cytoskeleton.

Actins↗
PubMed2001

Neurobiology.

Explore the source record for details and available documents.

Animals↗
PubMed2000

Stem cells: You make me feel so glial.

The signals that instruct neural stem cells to differentiate into glia have long proved elusive. Surprising new evidence suggests that this role could be fulfilled by Notch signalling, previously thought to be a general inhibitor of stem cell differentiation.

Animals↗
PubMed2000

Stimulation of human epidermal differentiation by delta-notch signalling at the boundaries of stem-cell clusters.

BACKGROUND: Human epidermis is renewed throughout life from stem cells in the basal layer of the epidermis. Signals from the surrounding keratinocytes influence the differentiation of the stem cells, but the nature of the signals is unknown. In many developing tissues, signalling mediated by the transmembrane protein Delta1 and its receptor Notch1 inhibits differentiation. Here, we investigated the role of Delta-Notch signalling in postnatal human epidermis. RESULTS: Notch1 expression was found in all living epidermal layers, but Delta1 expression was confined to the basal layer of the epidermis, with highest expression in those regions where stem cells reside. By overexpressing Delta1 or Delta(T), a truncated form of Delta1, in primary human keratinocytes and reconstituting epidermal sheets containing mixtures of Delta-overexpressing cells and wild-type cells, we found that cells expressing high levels of Delta1 or Delta(T) failed to respond to Delta signals from their neighbours. In contrast, wild-type keratinocytes that were in contact with neighbouring cells expressing Delta1 were stimulated to leave the stem-cell compartment and initiate terminal differentiation after a few rounds of division. Delta1 promoted keratinocyte cohesiveness, whereas Delta(T) did not. CONCLUSIONS: We propose that high Delta1 expression by epidermal stem cells has three effects: a protective effect on stem cells by blocking Notch signalling; enhanced cohesiveness of stem-cell clusters, which may discourage intermingling with neighbouring cells; and signalling to cells at the edges of the clusters to differentiate. Notch signalling in epidermal stem cells thus differs from other progenitor cell populations in promoting, rather than suppressing, differentiation.

Cell Differentiation↗
PubMed1999

The spatial relationship between stem cells and their progeny in the basal layer of human epidermis: a new view based on whole-mount labelling and lineage analysis.

In order to examine the spatial organisation of stem cells and their progeny in human epidermis, we developed a method for whole-mount epidermal immunofluorescence labelling using high surface beta1 integrin expression as a stem cell marker. We confirmed that there are clusters of high beta1 integrin-expressing cells at the tips of the dermal papillae in epidermis from several body sites, whereas alpha6 integrin expression is more uniform. The majority of actively cycling cells detected by Ki67 or bromodeoxyuridine labelling were found in the beta1 integrin-dull, transit amplifying population and integrin-negative, keratin 10-positive cells left the basal layer exclusively from this compartment. When we examined p53-positive clones in sun-exposed epidermis, we found two types of clone that differed in size and position in a way that was consistent with the founder cell being a stem or transit amplifying cell. The patterning of the basal layer implies that transit amplifying cells migrate over the basement membrane away from the stem cell clusters. In support of this, isolated beta1 integrin-dull keratinocytes were more motile on type IV collagen than beta1 integrin-bright keratinocytes and EGFP-labelled stem cell clones in confluent cultured sheets were compact, whereas transit amplifying clones were dispersed. The combination of whole-mount labelling and lineage marking thus reveals features of epidermal organisation that were previously unrecognised.

Biomarkers↗
PubMed1997

Transcription of tissue-specific genes in human preimplantation embryos.

We have recently detected de-novo transcripts of the predominantly muscle-specific myotonin protein kinase gene in human preimplantation embryos from the 1-cell to the 4-cell stages. Others have shown de-novo transcripts of the Y-linked genes, ZFY and SRY, in the 1-cell zygote. In order to assess the significance of early transcription of these predominantly tissue-specific genes in preimplantation development, we have analysed individual human oocytes and preimplantation embryos for the presence of transcripts of two further tissue-specific genes, alpha-globin and beta-globin, and two house-keeping genes, HPRT and APRT. Reverse transcriptase polymerase chain reaction assays were developed to the required single cell sensitivity, using human red blood cells and fibroblasts, prior to their application to human oocytes and embryos. As expected, transcripts of the house-keeping genes, HPRT and APRT, were detected at all stages of preimplantation development. Transcripts of 'tissue-specific' alpha-globin were readily detected in preimplantation embryos from the 1-cell stage. However, transcripts of beta-globin were detected only rarely (in only one of the 11 embryos analysed). This difference may be due to the fact that alpha-globin contains a CpG island. A survey of the data on gene expression in early human development suggests that CpG-island-containing genes may be expressed in preimplantation embryos. Expression of these genes in gametes and early embryos may be involved in the survival of CpG islands in evolution.

Adenine Phosphoribosyltransferase↗
PubMed1995

Effect of implicit and explicit "rule" presentation on bound-morpheme generalization in specific language impairment.

This study addressed whether generalization of a trained bound morpheme to untrained vocabulary stems differs between children with specific language impairment (SLI) and children with normal language (NL) under two controlled instructional conditions. Twenty-five children with NL and 25 children with SLI matched for age served as subjects. Contrasts between affixed and unaffixed words highlighted the affixation "rule" in the "implicit-rule" condition. The "rule" was verbalized by the trainer in the "explicit-rule" condition. Bimodal generalization results occurred in both subject groups, indicating that generalization was not incremental. Chi-square analyses suggested that the SLI group generalized the bound morpheme less often than the NL group under the explicit-rule training condition. The findings add to those that indicate children with SLI have a unique language-learning style, and suggest that the explicit presentation of metalinguistic information during training may be detrimental to bound-morpheme generalization by preschool-age children with SLI.

Child↗
PubMed1985

Nutrition and fertility in Bangladesh: nutritional status of nonpregnant women.

In October 1975 a longitudinal study of over 2000 married women was initiated in Matlab, Bangladesh, to determine the association of fertility with nutritional status. This paper reports the results on nutritional status among nonpregnant women. The average weight and height of the study women was 40.4 kg and 147.9 cm. Weight fluctuated throughout the 2 1/2 yr study period corresponding to seasonal food shortages. Maternal weight (controlling for height) was consistently lower for older, higher parity women, illustrating the negative impact of increasing numbers of births on the mother's nutrient stores. Older women were also shorter than younger women, due to greater deficits in growth during childhood. Older, higher parity women had slightly lower hematocrits than younger women with an overall mean of 35%. Education level was associated positively with height, weight, and hematocrit. Muslims were taller and heavier than Hindus, reflecting their generally higher socioeconomic status. The seasonal pattern of nutritional status is discussed in relation to the seasonality of food availability, activity patterns, and incidence of infectious disease.

Adolescent↗
PubMed1981

Cellular uptake of L-lactate in mouse diaphragm.

Early uptake curves of L-lactate and of mannitol were measured in quartered, incubated mouse diaphragms. Uptake was determined at 15, 30, and 45 s for various concentrations of lactate in the external solution as well as in the presence and absence of the competitive inhibitor of lactate transport, alpha-cyano-4-hydroxycinnimate. In normal preparations, when the external lactate concentration was 10 mM or less, the ratio of lactate-to mannitol space in the tissue was 1.7. This value was nearly independent of time and of external concentration. In normal preparations, when the external lactate concentration was greater than 10 mM, the ratio of lactate-to-mannitol space rose with time. At a fixed time, however, this ratio fell with increasing lactate concentration. In the inhibited preparations, the ratio of lactate-to-mannitol space rose with time at all concentrations. When lactate concentration was greater than 5 mM, this ratio was independent of the external concentration. The results suggest that there are two modes of lactate entry into these muscle cells. Entry can occur by means of a saturable system. When external lactate concentration is low, entry rates for this process are rapid compared with diffusional rates. This system probably saturates at concentrations near 10 mM and can facilitate transport in either direction. In addition, an appreciable passive leak is present. This leak accounts for about one fourth of the membrane transfer when external lactate is low, but is equal to the carrier transfer when lactate concentration is 30 mM. A model was developed to describe the entry of a permeating solute, such as lactate, into an isolated tissue.

Animals↗