A PRELIMINARY COMPARISON OF MITOCHONDRIAL D-LOOP REGION OF FUNAAB ALPHA AND NIGERIAN INDIGENOUS CHICKENS

Nigerian indigenous chickens possess immunity from endemic diseases and have a better survival rate than commercial hybrid strains under local production conditions. FUNAAB Alpha chicken was developed by improving Nigerian indigenous chickens through crossbreeding and selection. This study compared the mitochondrial d-loop of FUNAAB Alpha and Nigerian indigenous chickens to check likely genetic erosion and loss of diversity in development of FUNAAB Alpha breed. Blood samples were collected from Nigerian indigenous (n=23) and FUNAAB Alpha (n=20) chickens sampled from farms and houses in Ogun state, Nigeria. The Hypervariable 1 (HV1) of the mitochondrial d-loop region was amplified and sequenced. Single nucleotide polymorphisms present in HV1 of chickens were identified using Clustal W. Genetic diversity of the region was determined using DnaSp v5 while selective forces acting on the chickens were predicted using HyPhy software implemented inside MEGA 6 software. Phylogenetic relationship among FUNAAB Alpha, Nigerian indigenous and other chicken breeds was determined using MEGA 6 software. Five polymorphisms were identified in FUNAAB Alpha chickens while twelve were identified in Nigerian indigenous chickens. All the polymorphisms identified in FUNAAB Alpha chickens were also observed in Nigerian indigenous chickens while seven polymorphisms were unique to Nigerian indigenous chickens. Higher diversity indices were observed in Nigerian indigenous chickens (number of haplotype: 4; haplotype diversity: 0.743±0.012; nucleotide diversity: 0.014±0.0013 and average number of nucleotide differences: 4.332) compared with FUNAAB Alpha chickens (number of haplotype: 2; haplotype diversity: 0.485±0.001; nucleotide diversity: 0.008±0.0001 and average number of nucleotide differences: 2.424). Positive selective forces were acting on FUNAAB Alpha chickens while negative selective forces were acting on Nigerian indigenous chickens. Phylogenetic analysis revealed that FUNAAB Alpha chickens clustered with Nigerian indigenous and South American chickens. It can be concluded that there was likely genetic erosion and loss of diversity in development of FUNAAB Alpha breed. Breeding programmes aimed at improvement of genetic diversity and reduction of genetic erosion should be applied in subsequent improvement of FUNAAB Alpha chickens

Collecting biological material from palliative care patients in the last weeks of life: a feasibility study

Objective To assess the feasibility of prospectively collecting biological samples (urine) from palliative care patients in the last weeks of life. Setting A 30-bedded specialist hospice in the North West of England. Participants Participants were adults with a diagnosis of advanced disease and able to provide written informed consent. Method Potential participants were identified by a senior clinician over a 12-week period in 2014. They were then approached by a researcher and invited to participate according to a developed recruitment protocol. Outcomes Feasibility targets included a recruitment rate of 50%, with successful collection of samples from 80% who consented. Results A total of 58 patients were approached and 33 consented (57% recruitment rate). Twenty-five patients (43%) were unable to participate or declined; 10 (17%) became unwell, too fatigued, lost capacity, died or were discharged home; and 15 (26%) refused, usually these patients had distressing pain, low mood or profound fatigue. From the 33 recruited, 20 participants provided 128 separate urine samples, 12 participants did not meet the inclusion criteria at the time of consent and 1 participant was unable to provide a sample. The criterion for a urinary catheter was removed for the latter 6 weeks. The collection rate during the first 6 weeks was 29% and 93% for the latter 6 weeks. Seven people died while the study was ongoing, and another 4 participants died in the following 4 weeks. Conclusions It is possible to recruit and collect multiple biological samples over time from palliative care patients in the last weeks and days of life even if they have lost capacity. Research into the biological changes at the end of life could develop a greater understanding of the biology of the dying process. This may lead to improved prognostication and care of patients towards the end of life

GC-MS Techniques Investigating Potential Biomarkers of Dying in the Last Weeks with Lung Cancer

Predicting when a patient with advanced cancer is dying is a challenge and currently no prognostic test is available. We hypothesised that a dying process from cancer is associated with metabolic changes and specifically with changes in volatile organic compounds (VOCs). We analysed urine from patients with lung cancer in the last weeks of life by headspace gas chromatography mass spectrometry. Urine was acidified or alkalinised before analysis. VOC changes in the last weeks of life were identified using univariate, multivariate and linear regression analysis; 12 VOCs increased (11 from the acid dataset, 2 from the alkali dataset) and 25 VOCs decreased (23 from the acid dataset and 3 from the alkali dataset). A Cox Lasso prediction model using 8 VOCs predicted dying with an AUC of 0.77, 0.78 and 0.85 at 30, 20 and 10 days and stratified patients into a low (median 10 days), medium (median 50 days) or high risk of survival. Our data supports the hypothesis there are specific metabolic changes associated with the dying. The VOCs identified are potential biomarkers of dying in lung cancer and could be used as a tool to provide additional prognostic information to inform expert clinician judgement and subsequent decision making

Ceramide-induced integrated stress response overcomes Bcl-2 inhibitor resistance in acute myeloid leukemia.

Inducing cell death by the sphingolipid ceramide is a potential anti-cancer strategy, but the underlying mechanisms remain poorly defined. Here, we show that triggering accumulation of ceramide in acute myeloid leukaemia (AML) cells by inhibition of sphingosine kinase induces an apoptotic integrated stress response (ISR) through protein kinase R-mediated activation of the master transcription factor ATF4. This leads to transcription of the BH3-only protein, Noxa, and degradation of the pro-survival Mcl-1 protein on which AML cells are highly dependent on for survival. Targeting this novel ISR pathway in combination with the Bcl-2 inhibitor venetoclax synergistically killed primary AML blasts, including those with venetoclax-resistant mutations, as well as immunophenotypic leukemic stem cells, and reduced leukemic engraftment in patient-derived AML xenografts. Collectively, these findings provide mechanistic insight into the anti-cancer effects of ceramide and pre-clinical evidence for new approaches to augment Bcl-2 inhibition in the therapy of AML and other cancers with high Mcl-1 dependency.Alexander C. Lewis, Victoria S. Pope, Melinda N. Tea, Manjun Li, Gus O. Nwosu, Thao M. Nguyen, Craig T. Wallington-Beddoe, Paul A. B. Moretti, Dovile Anderson, Darren J. Creek, Maurizio Costabile, Saira R. Ali, Chloe A. L. Thompson-Peach, B. Kate Dredge, Andrew G. Bert, Gregory J. Goodall, Paul G. Ekert, Anna L. Brown, Richard D'Andrea, Nirmal Robinson, Melissa R. Pitman, Daniel Thomas, David M. Ross, Briony L. Gliddon, Jason A. Powell, and Stuart M. Pitso

World Economic Recession and the Ascendancy of Protectionism: The Case of the Nigerian Agricultural Sector

Barners to agricultural trade durmg the colonial era and up to 1961 were imposed mamly to raise revenue. Accordingly, the barriers were export taxes rather than import tariffs. With the adoption of import substitution as a development philosophy, a more aggressive tariff pohcy was pursued. Thus, s1gn1f1cant increases in tariff rates occurred between 1967 and 1974. The decline in petroleum export earnings of the late 1970s and early 1980s, however, precipitated a rise in protectiomsm in which tanffs were remforced bystrmgent quantitative controls. The effects have been acute shortages of basic commod1ties, unprecedented mflatmn, and growing unemployment

Market liberalization and its effects on Nigerian agriculture

Partial final repor

Relative Technical Efficiency of Credit and Non-credit User Crop Farmers

Credit has become a prominent resource in agriculture production in Nigeria in an effort to redress resource poverty endemic among the farming populace. Formal and informal credit schemes have been established, however, their success in addressing the credit needs of food crop farmers remains a matter of debate. This study was designed to examine the impact of rural credit on resource use in arable crop production in Imo State of Nigeria. Primary data collected from random samples of 132 arable crop farmers consisting of 57 credit using and 75 non-credit using farmers were used. Data were analyzed using the stochastic frontier production function modeling. It is evident that credit using farmers are more technically efficient than their non-credit using counterparts. Age of the farmer, household size, level of formal education, farming experience and membership of farmer associations/cooperatives were statistically significant factors influencing technical efficiency. The ranges of technical efficiency were 0.131 to 0.951 for the credit using farmers, and 0.311 to 0.941 for the non-credit using farmers. The mean technical efficiency for the 10 worst performing farmers was 0.157 for the credit users and 0.185 for the non-credit users. Values for the 10 best performing farmers were 0.749 for the credit and 0.886 for the non-credit users. It would take an average credit using farmer 64 percent cost savings and an average non-credit using farmer 50 percent cost savings to become the best performing farmers in their respective groups. Based on these results, appropriate policies and programmes that could strengthen the farmers' participation in rural credit markets and for enhancing their efficiency in resource use are recommended