Exploring homeless people’s use of outreach services: applying a social psychological perspective

A number of critiques have been published drawing attention to the gaps in research methods applied to issues surrounding homelessness and service utilisation in Britain. This paper discusses the use of social identity, a theory drawn from the field of applied social psychology, and synthesises it with the pathways model, thereby providing a framework to further explore service utilisation. The synthesised framework was used to predict the uptake of outreach services in a prospective study of 121 homeless people in a major UK city. In general, homeless people's use of intervention services was affected by the extent to which they identified with the support services themselves. The study demonstrates the central role of social identity in understanding service utilisation patterns, and shows the importance of applying fresh techniques to fine-tune our understanding of uptake in the long term.

Sources of sulphur in gypsiferous sediments and crusts and pathways of gypsum redistribution in southern Tunisia

Southern Tunisia contains one of the most extensive gypsum accumulations in Africa comprising Triassic, Cretaceous, Eocene and Mio-Pliocene marine evaporites, spring deposits, playa sediments, aeolian sands and gypsum crusts. Sulphur isotope analysis (delta(34)S) of bedrock samples, groundwater, playa brines, playa sediments, and gypsiferous crusts provides insight into the sources of gypsum in the region and sheds light on the processes that lead to gypsum crust formation. Results Suggest that recycling of marine gypsum is the most likely source of the sulphate in the groundwater, playa sediments and crusts. The low PS values found in Eocene and Mio-Pliocene samples suggest that this recycling has been going on for millions of years. Though bedrock appears to be the ultimate source of the gypsum in the crusts, transport of this sulphate to playas, concentration therein, and subsequent dispersal across the landscape by aeolian processes provides the most likely pathway for surticial gypsum crust formation. Comparison of these results with those from Australia, Chile and Namibia suggests that, although the source of the sulphur varies from region to region, the processes of surficial crust formation appear to be similar. Copyright (C) 2004 John Wiley Sons, Ltd.

Promoting resilience and protective factors in the Children's Fund: supporting children and young people's pathways towards social inclusion?

As part of the broader prevention and social inclusion agenda, concepts of risk, resilience, and protective factors inform a range of U.K. Government initiatives targeted towards children and young people in England, including Sure Start, the Children's Fund, On Track, and Connexions. This paper is based on findings from a large qualitative dataset of interviews conducted with children and their parents or caregiver who accessed Children's Fund services as part of National Evaluation of the Children's Fund research.1 Drawing on the notion of young people's trajectories, the paper discusses how Children's Fund services support children's and young people's pathways towards greater social inclusion. While many services help to build resilience and protective factors for individual children, the paper considers the extent to which services also promote resilience within the domains of the family, school, and wider community and, hence, attempt to tackle the complex, multi-dimensional aspects of social exclusion affecting children, young people, and their families.

Uptake Pathways of Polycyclic Aromatic Hydrocarbons in White Clover

An understanding of the primary pathways of plant uptake of organic pollutants is important to enable the risks from crops grown on contaminated soils to be assessed. A series of experiments were undertaken to quantify the importance of the pathways of contamination and the Subsequent transport within the plant using white clover plants grown in solution culture. Root uptake was primarily an absorption process, but a component of the contamination was a result of the transpiration flux to the shoot for higher Solubility compounds. The root contamination can be easily predicted using a simple relationship with K-OW, although if a composition model was used based on lipid content, a significant under prediction of the contamination was observed. Shoot uptake was driven by the transpiration stream flux which was related to the solubility of the individual PAH rather than the K-OW. However, the experiment was over a short duration, 6 days, and models based on K-OW may be better for crops grown in the field where the vegetation will approach equilibrium and transpiration cannot easily be measured, A significant fraction of the shoot contamination resulted from aerial deposition derived from volatilized PAH. This pathway was more significant for compounds approaching log K-OA > 9 and log K-AW < -3. The shoot uptake pathways need further investigation to enable them to be modeled separately, There was no evidence of significant systemic transport of the PAR so transfer outside the transpiration stream is likely to be limited.

Analysis of water-level response to rainfall and implications for recharge pathways in the Chalk aquifer, SE England

Water table response to rainfall was investigated at six sites in the Upper, Middle and Lower Chalk of southern England. Daily time series of rainfall and borehole water level were cross-corretated to investigate seasonal variations in groundwater-level response times, based on periods of 3-month duration. The time tags (in days) yielding significant correlations were compared with the average unsaturated zone thickness during each 3-month period. In general, for cases when the unsaturated zone was greater than 18 m thick, the time tag for a significant water-level response increased rapidly once the depth to the water table exceeded a critical value, which varied from site to site. For shallower water tables, a linear relationship between the depth to the water table and the water-level response time was evident. The observed variations in response time can only be partially accounted for using a diffusive model for propagation through the unsaturated matrix, suggesting that some fissure flow was occurring. The majority of rapid responses were observed during the winter/spring recharge period, when the unsaturated zone is thinnest and the unsaturated zone moisture content is highest, and were more likely to occur when the rainfall intensity exceeded 5 mm/day. At some sites, a very rapid response within 24 h of rainfall was observed in addition to the longer term responses even when the unsaturated zone was up to 64 m thick. This response was generally associated with the autumn period. The results of the cross-correlation analysis provide statistical support for the presence of fissure flow and for the contribution of multiple pathways through the unsaturated zone to groundwater recharge. (c) 2006 Elsevier B.V. All rights reserved.

Identifying seed uptake pathways: The spread of Agya amoah rice cultivar in southwestern Ghana

A study was carried out to identify the factors that contributed to the natural spread and uptake of a rainfed rice variety named Agya Amoah in the Western Region of Ghana after introduction of a small amount (0.5 kg) of seed in 1987 by a small-scale farmer. Fifteen years after its introduction over 73% of rice farmers had grown the variety in the Western Region. Initial awareness of the variety was created by information provided mainly by friends, seeing the variety grown in fields and from relatives. Seed for initial planting of the variety was purchased from other farmers by 67% of farmers, but in the most recent season 77% of farmers used their own saved seed. Annual incremental income per household from the replacement of the previously most widely grown variety with Agya Amoah was estimated to be US $282. The results show that informal systems can result in relatively fast spread and extensive uptake. Local seed systems need to be understood to design appropriate activities that are likely to lead to rapid spread and equitable distribution of introduced varieties, irrespective of characteristics such as wealth and kin.

Uptake pathways: the potential of Bayesian belief networks to assist the management, monitoring and evaluation of development-orientated research

The effectiveness of development assistance has come under renewed scrutiny in recent years. In an era of growing economic liberalisation, research organisations are increasingly being asked to account for the use of public funds by demonstrating achievements. However, in the natural resources (NR) research field, conventional economic assessment techniques have focused on quantifying the impact achieved rather understanding the process that delivered it. As a result, they provide limited guidance for planners and researchers charged with selecting and implementing future research. In response, “pathways” or logic models have attracted increased interest in recent years as a remedy to this shortcoming. However, as commonly applied these suffer from two key limitations in their ability to incorporate risk and assess variance from plan. The paper reports the results of a case study that used a Bayesian belief network approach to address these limitations and outlines its potential value as a tool to assist the planning, monitoring and evaluation of development-orientated research.

A functional genomics approach reveals novel quantitative trait loci associated with platelet signalling pathways

Platelet response to activation varies widely between individuals but shows interindividual consistency and strong heritability. The genetic basis of this variation has not been properly explored. We therefore systematically measured the effect on function of sequence variation in 97 candidate genes in the collagen and adenosine-diphosphate (ADP) signaling pathways. Resequencing of the genes in 48 European DNA samples nearly doubled the number of known single nucleotide polymorphisms (SNPs) and informed the selection of 1327 SNPs for genotyping in 500 healthy Northern European subjects with known platelet responses to collagen-related peptide (CRP-XL) and ADP. This identified 17 novel associations with platelet function (P < .005) accounting for approximately 46% of the variation in response. Further investigations with platelets of known genotype explored the mechanisms behind some of the associations. SNPs in PEAR1 associated with increased platelet response to CRP-XL and increased PEAR1 protein expression after platelet degranulation. The minor allele of a 3' untranslated region (UTR) SNP (rs2769668) in VAV3 was associated with higher protein expression (P = .03) and increased P-selectin exposure after ADP activation (P = .004). Furthermore the minor allele of the intronic SNP rs17786144 in ITPR1 modified Ca2+ levels after activation with ADP (P < .004). These data provide novel insights into key hubs within platelet signaling networks.

PECAM-1 expression and activity negatively regulate multiple platelet signaling pathways

Platelet endothelial cell adhesion molecule-1 (PECAM-1) inhibits platelet response to collagen and may also inhibit two other major platelet agonists ADP and thrombin although this has been less well explored. We hypothesized that the combined effect of inhibiting these three platelet activating pathways may act to significantly inhibit thrombus formation. We demonstrate a negative relationship between PECAM-1 surface expression and platelet response to cross-linked collagen related peptide (CRP-XL) and ADP, and an inhibitory effect of PECAM-1 clustering on platelet response to CRP-XL, ADP and thrombin. This combined inhibition of multiple signaling pathways results in a marked reduction in thrombus formation. (C) 2009 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

Intracellular signalling pathways regulating the adaptation of skeletal muscle to exercise and nutritional changes

The focus of the present review is to assimilate current knowledge concerning the differing signalling transduction cascades that control muscle mass development and affect skeletal muscle phenotype following exercise or nutritional uptake. Effects of mechanical loading on protein synthesis are discussed. Muscle growth control is regulated by the interplay of growth promoting and growth suppressing factors, which act in concert. Much emphasis has been placed on understanding how increases in the rate of protein synthesis are induced in skeletal muscle during the adaptive process. One key point to emerge is that protein synthesis following resistance exercise or increased nutrient availability is mediated through changes in signal transduction involving the phosphorylation of mTOR and sequential activation of downstream targets. On the other hand, AMPK activation plays an important role in the inhibition of protein synthesis by suppressing the function of multiple translation regulators of the mTOR signalling pathway in response to cellular energy depletion and low metabolic conditions. The effects of exercise and/or nutritional uptake on the activation of signalling molecules that regulate protein synthesis are highlighted, providing a better understanding of the molecular changes in the cell.

The stimulation of mitogenic signaling pathways by N-POMC peptides

The N-terminal fragment of pro-opiomelancortin (POMC) has been shown previously to act as an adrenal mitogen. However, little is known about the molecular mechanisms by which mitogenesis is stimulated, although it has been shown that N-POMC1-28 Stimulates the ERK pathway in human H295R cells. We have investigated signaling stimulated by N-POMC1-28 and N-POMC1-49 in the mouse Y1 cell line and found that both peptides stimulate ERK phosphorylation with maximal stimulation being achieved within 5 min. Similar results were observed for both MEK and c-Raf phosphorylation, although N-POMC1-49 stimulated the phosphorylation of Akt more robustly than N-POMC1-28. We also investigated the expression of tyrosine kinase receptors in adrenal cells. PCR utilizing degenerate primers was performed on cDNA from both Y1 cells and rat adrenal tissue. Sequencing of 114 clones from each cDNA population revealed the expression of a number of receptors, several of which have not been described previously in the adrenal. (C) 2008 Elsevier Ireland Ltd. All rights reserved.

Functional significance of the signal transduction pathways Akt and Erk in ovarian follicles: in vitro and in vivo studies in cattle and sheep

BACKGROUND: The intracellular signalling mechanisms that regulate ovarian follicle development are unclear; however, we have recently shown differences in the Akt and Erk signalling pathways in dominant compared to subordinate follicles. The aim of this study was to investigate the effects of inhibiting Akt and Erk phosphorylation on IGF- and gonadotropin- stimulated granulosa and theca cell function in vitro, and on follicle development in vivo. METHODS: Bovine granulosa and theca cells were cultured for six days and stimulated with FSH and/or IGF, or LH in combination with PD98059 (Erk inhibitor) and/or LY294002 (Akt inhibitor) and their effect on cell number and hormone secretion (estradiol, activin-A, inhibin-A, follistatin, progesterone and androstenedione) determined. In addition, ovarian follicles were treated in vivo with PD98059 and/or LY294002 in ewes on Day 3 of the cycle and follicles were recovered 48 hours later. RESULTS: We have shown that gonadotropin- and IGF-stimulated hormone production by granulosa and theca cells is reduced by treatment with PD98059 and LY294002 in vitro. Furthermore, treatment with PD98059 and LY294002 reduced follicle growth and oestradiol production in vivo. CONCLUSION: These results demonstrate an important functional role for the Akt and Erk signalling pathways in follicle function, growth and development.

Platelet 12-lipoxygenase activation via glycoprotein VI: involvement of multiple signaling pathways in agonist control of H(P)ETE synthesis

Lipoxygenases (LOX) contribute to vascular disease and inflammation through generation of bioactive lipids, including 12-hydro(pero xyeicosatetraenoic acid (12-H(P)ETE). The physiological mechanisms that acutely control LOX product generation in mammalian cells are uncharacterized. Human platelets that contain a 12-LOX isoform (p12-LOX) were used to define pathways that activate H(P)ETE synthesis in the vasculature. Collagen and collagen-related peptide (CRP) (1 to 10 g/mL) acutely induced platelet 12-H(P)ETE synthesis. This implicated the collagen receptor glycoprotein VI (GPVI), which signals via the immunoreceptor-based activatory motif (ITAM)- containing FcR chain. Conversely, thrombin only activated at high concentrations ( 0.2 U/mL), whereas U46619 and ADP alone were ineffective. Collagen or CRP-stimulated 12-H(P)ETE generation was inhibited by staurosporine, PP2, wortmannin, BAPTA/AM, EGTA, and L-655238, implicating src-tyrosine kinases, PI3-kinase, Ca2 mobilization, and p12-LOX translocation. In contrast, protein kinase C (PKC) inhibition potentiated 12-H(P)ETE generation. Finally, activation of the immunoreceptor tyrosine-based inhibitory motif (ITIM)– containing platelet endothelial cell adhesion molecule (PECAM-1) inhibited p12-LOX product generation. This study characterizes a receptor-dependent pathway for 12-H(P)ETE synthesis via the collagen receptor GPVI, which is negatively regulated by PECAM-1 and PKC, and demonstrates a novel link between immune receptor signaling and lipid mediator generation in the vasculature. (Circ Res. 2004;94:1598-1605.)

Exchangeability of mammalian DNA ligases between base excision repair pathways

In mammalian cells, DNA ligase IIIalpha and DNA ligase I participate in the short- and long-patch base excision repair pathways, respectively. Using an in vitro repair assay employing DNA ligase-depleted cell extracts and DNA substrates containing a single lesion repaired either through short-patch (regular abasic site) or long-patch (reduced abasic site) base excision repair pathways, we addressed the question whether DNA ligases are specific to each pathway or if they are exchangeable. We find that immunodepletion of DNA ligase I did not affect the short-patch repair pathway but blocked long-patch repair, suggesting that DNA ligase IIIa is not able to substitute DNA ligase I during long-patch repair. In contrast, immunodepletion of DNA ligase IIIa did not significantly affect either pathway. Moreover, repair of normal abasic sites in wild-type and X-ray cross-complementing gene 1 (XRCC1)-DNA ligase IIIalpha-immunodepleted cell extracts involved similar proportions of short- and long-patch repair events. This suggests that DNA ligase I was able to efficiently substitute the XRCC1-DNA ligase IIIa complex during short-patch repair.