Inhibition of integrin-mediated crosstalk with epidermal growth factor receptor/Erk or Src signaling pathways in autophagic prostate epithelial cells induces caspase-independent death

In vivo in the prostate gland, basal epithelial cells adhere to laminin 5 (LM5) via alpha3beta1 and alpha6beta4 integrins. When placed in culture primary prostate basal epithelial cells secrete and adhere to their own LM5-rich matrix. Adhesion to LM5 is required for cell survival that is dependent on integrin-mediated, ligand-independent activation of the epidermal growth factor receptor (EGFR) and the cytoplasmic tyrosine kinase Src, but not PI-3K. Integrin-mediated adhesion via alpha3beta1, but not alpha6beta4 integrin, supports cell survival through EGFR by signaling downstream to Erk. PC3 cells, which do not activate EGFR or Erk on LM5-rich matrices, are not dependent on this pathway for survival. PC3 cells are dependent on PI-3K for survival and undergo caspase-dependent death when PI-3K is inhibited. The death induced by inhibition of EGFR or Src in normal primary prostate cells is not mediated through or dependent on caspase activation, but depends on the induction of reactive oxygen species. In addition the presence of an autophagic pathway, maintained by adhesion to matrix through alpha3beta1 and alpha6beta4, prevents the induction of caspases when EGFR or Src is inhibited. Suppression of autophagy is sufficient to induce caspase activation and apoptosis in LM5-adherent primary prostate epithelial cells.     

Natural and within-farmland biodiversity enhances crop productivity

Ongoing expansion of large-scale agriculture critically threatens natural habitats and the pollination services they offer. Creating patches with high plant diversity within farmland is commonly suggested as a measure to benefit pollinators. However, farmers rarely adopt such practice, instead removing naturally occurring plants (weeds). By combining pollinator exclusion experiments with analysis of honeybee behaviour and flower-visitation webs, we found that the presence of weeds allowed pollinators to persist within sunflower fields, maximizing the benefits of the remaining patches of natural habitat to productivity of this large-scale crop. Weed diversity increased flower visitor diversity, hence ameliorating the measured negative effects of isolation from natural habitat. Although honeybees were the most abundant visitors, diversity of flower visitors enhanced honeybee movement, being the main factor influencing productivity. Conservation of natural patches combined with promoting flowering plants within crops can maximize productivity and, therefore, reduce the need for cropland expansion, contributing towards sustainable agriculture.     

Ferritin blocks inhibitory effects of two-chain high molecular weight kininogen (HKa) on adhesion and survival signaling in endothelial cells

Angiogenesis is tightly regulated through complex crosstalk between pro- and anti-angiogenic signals. High molecular weight kininogen (HK) is an endogenous protein that is proteolytically cleaved in plasma and on endothelial cell surfaces to HKa, an anti-angiogenic protein. Ferritin binds to HKa and blocks its anti-angiogenic activity. Here, we explore mechanisms underlying the cytoprotective effect of ferritin in endothelial cells exposed to HKa. We observe that ferritin promotes adhesion and survival of HKa-treated cells and restores key survival and adhesion signaling pathways mediated by Erk, Akt, FAK and paxillin. We further elucidate structural motifs of both HKa and ferritin that are required for effects on endothelial cells. We identify an histidine-glycine-lysine (HGK) -rich antiproliferative region within domain 5 of HK as the target of ferritin, and demonstrate that both ferritin subunits of the H and L type regulate HKa activity. We further demonstrate that ferritin reduces binding of HKa to endothelial cells and restores the association of uPAR with α5β1 integrin. We propose that ferritin blocks the anti-angiogenic activity of HKa by reducing binding of HKa to UPAR and interfering with anti-adhesive and anti-proliferative signaling of HKa.     

Field-based investigation on phytoremediation potentials of Lemna minor and Azolla filiculoides in tropical,semiarid regions: Case of Ethiopia

This study investigated the concurrent accumulation of eight heavy metals by two floating aquatic macrophytes (Lemna minor and Azolla filiculoides) cultivated in ambient media and blended wastewaters in the semiarid regions of Ethiopia. Both species accumulated heavy metals in varying degrees with a significant concentration gradient within the immediate water media. Highest bioconcentration factor (BCF) was determined for Mn and Fe in both plants. Results revealed that L. minor was high phytoaccumulator for Fe, Mn, Zn, and Co but moderate for Cd, Cu, Ni, and Cr. On the other hand, A. filiculoides was a high accumulator for Fe, Mn, Zn, and Cu, but its potency was moderate for Co, Cr, and Ni, but lower for Cd. Both species exhibited significant difference in accumulating Co, Zn, and Mn (p < 0.05). In general, the BCFs for both plants were comparable within the same treatment. In this study, stronger associations between the heavy metal concentrations in the plant tissues and in the grown water media were observed for A. filiculoides.     

Factors associated with uptake of post-abortion family planning in Shire town,Tigray, Ethiopia

Objectives

Post-abortion contraceptive service is pivotal for the prevention of unwanted pregnancy and alleviation of its complication. Worldwide half of the pregnancy is unplanned, whereas unwanted pregnancy ends up with abortion. This study assessed post-abortion contraceptive uptake and associated factors among abortion service users at health institution in Shire town, North Ethiopia. Institutional based cross-sectional study was conducted from December 15/2016 to March 15, 2017, in Shire town. Data were collected using systematic random sampling technique. Bivariate and multivariable analyses were done to determine the association of each independent variable with the dependent variable.

Results

Overall post-abortion contraceptive utilization in this study was 61.5%. Married [AOR 2.59, 95% CI (1.16, 5.65)], completed College education [AOR 5.69, 95% CI (1.61, 20.11)], previous contraceptive used [AOR 3.62, 95% CI (1.77, 7.40)], counseling of family planning [AOR 3.53 95% CI (1.69, 7.37)], grand multipara [AOR 7.91, 95% CI (1.66, 37.74)] and public health institution [AOR 5.95, 95% CI (3.03, 11.72)] were significantly associated with the post-abortion contraceptive utilization. In this study, post-abortion contraceptive utilization was about two-third. Being married, had been completing a college education, had been receiving family planning counseling, previous contraceptive usage, abortion care service at public health institution, and being grand multiparty were determinants of post-abortion contraceptive utilization.

     

The community-based malaria control programme in Tigray, northern Ethiopia. A review of programme set-up, activities, outcomes and impact.

Tigray, the northernmost state of Ethiopia, has a population of 3.5 million, 86% rural, and 56% living in malarious areas. In 1992 a Community-Based Malaria Control Programme was established to provide region-wide and sustained access to early diagnosis and treatment of malaria at the village level. 735 volunteer community health workers (CHWs) serve 2,327 villages with a population of 1.74 million, treating an average of 489,378 patients yearly from 1994 to 1997. Recognition of clinical malaria is similar for CHWs and health staff at clinics where there is no access to microscopy. In 1996 a pilot community-financing scheme of insecticide-treated bednets was well accepted, but re-impregnation rates fell in 1998 because of war-related social upheaval. Indicators from health institutions show a progressive increase in malaria morbidity from 1994 to 1998. Repeated mortality surveys show a 40% reduction in death rates in under-5 children from 1994 to 1996 and a 10% increase from 1996 to 1998. These trends may be related to increased malaria transmission with water resources development, increased seasonal labour migration to malarious lowlands, prolongation of the transmission season with climate changes, and increasing chloroquine resistance throughout Ethiopia. Progressive extension of CHW services to ensure better coverage of women, children, migrant workers and communities near water development projects, change to first-line treatment with sulfadoxine-pyrimethamine, extension of the impregnated bednet initiative, and development of a regional warning system for epidemics should result in a greater impact on morbidity and mortality.     

Health Extension Workers' and Mothers' Attitudes to Maternal Health Service Utilization and Acceptance in Adwa Woreda,Tigray Region,Ethiopia

Background

The maternal health system in Ethiopia links health posts in rural communities (kebeles) with district (woreda) health centres, and health centres with primary hospitals. At each health post two Health Extension Workers (HEWs) assist women with birth preparedness, complication readiness, and mobilize communities to facilitate timely referral to mid-level service providers. This study explored HEWs’ and mother’s attitudes to maternal health services in Adwa Woreda, Tigray Region.

Methods

In this qualitative study, we trained 16 HEWs to interview 45 women to gain a better understanding of the social context of maternal health related behaviours. Themes included barriers to health services; women’s social status and mobility; and women’s perceptions of skilled birth attendant’s care. All data were analyzed thematically.

Findings

There have been substantial efforts to improve maternal health and reduce maternal mortality in Adwa Woreda. Women identified barriers to healthcare including distance and lack of transportation due to geographical factors; the absence of many husbands due to off-woreda farming; traditional factors such as zwar (some pregnant women are afraid of meeting other pregnant women), and discouragement from mothers and mothers-in-law who delivered their children at home. Some women experienced disrespectful care at the hospital. Facilitators to skilled birth attendance included: identification of pregnant women through Women’s Development Groups (WDGs), and referral by ambulance to health facilities either before a woman’s Expected Due Date (EDD) or if labour started at home.

Conclusion

With the support of WDGs, HEWs have increased the rate of skilled birth attendance by calling ambulances to transfer women to health centres either before their EDD or when labour starts at home. These findings add to the growing body of evidence that health workers at the community level can work with women’s groups to improve maternal health, thus reducing the need for emergency obstetric care in low-income countries.     

Nucleotide sequences of genes encoding heat-stable and heat-labile glyceraldehyde-3-phosphate dehydrogenases; amino acid sequence and protein thermostability

The structural gene (gapST) encoding glyceraldehyde-3-phosphate dehydrogenase (GPDH; EC 1.2.1.12) from Bacillus stearothermophilus has been cloned in Escherichia coli using plasmid pBR322 as a vector; the homologous gene (gapCO) from Bacillus coagulans was cloned from a phage lambda library. Expression of the cloned gap genes revealed that, as in the wild-type (wt) organisms, the GPDH from B. stearothermophilus (GPDH-ST) was intrinsically heat stable (hs) and that from B. coagulans (GPDH-CO) heat labile (hl). The cloned gap genes were sequenced and the deduced amino acid (aa) sequences were found to be highly conserved (91.6% homology), despite the large difference in thermostability between these two enzymes. Of the 28 aa which differ between the two proteins, most of which occur in the middle third of the monomeric subunit, 5 aa involve replacement of alanine in the hl GPDH-CO, by proline in the hs GPDH-ST, and are especially interesting in terms of their potential contributions to thermostability. Conservation at the DNA level is equally dramatic, with the two gap genes exhibiting 93.3% nucleotide sequence homology. These highly expressed genes exhibit an equivalent codon bias, which more closely resembles that of highly expressed E. coli genes, than that of B. stearothermophilus genes whether highly or weakly expressed.