Tolerance of early life stages of Tilapia (Cichlidae: Tilapiini) to metal stress

Ecophysiological indices that characterise animals fitness directly or indirectly measure the components of protein turnover and its associated metabolic costs, Therefore, more likely protein turnover and associated metabolic costs may play a major role in underlying stress tolerance mechanisms. In this thesis a flow-through system was designed and developed to overcome some of the existing basic design flaws in such systems and used to determine responses of different species of' tilapiine fishes (Cichlidae: Tilapiini) under lethal and non-lethal stress using cadmium and copper. A significant variation in tolerance capability between mouth brooding and substrate spawning tilapia yolk sac-fry to lethal cadmium and copper stress was observed. There was concordance between the relative tolerance capabilities of these two groups to the two metals suggesting a general response. Similarly, tolerance capabilities were in concordance with early life-history growth traits and ass associated metabolic costs measured under non-stressed (control) conditions suggesting individuals with higher growth rates and low maintenance metabolic costs are better capable of tolerating metal stress than the individuals with low growth rates and higher maintenance metabolic costs. Lower cadmium body burden levels were observed in the sac-fry of the more tolerant substrate-spawner T zillii than those of in the more sensitive mouth- brooder () niloticus. Variations in growth performances between mouthbrooders and substrate spawners were attributed to the difference in their developmental rates. Therefore, genetically based phenotypic variations for early life history traits translate into variations in stress tolerance. Similarly O niloticus yolk sac-fry originating from small eggs were more tolerant to cadmium stress and had lower body burdens than larger conspecifics originating from large eggs. The early life history growth traits and associated metabolic costs measured under non-stress conditions were in concordance with the tolerance capabilities of the two size groups supporting the correlation between higher tolerance and low maintenance metabolic cost. The size of the yolk sac-fry was influenced by maternal age and size, and hence, by egg size. Therefore, translation of pre-determined phenotypic variations for early life history traits into variations in tolerance capabilities to metal lethal stress was supported. Starvation-induced reductions in metabolic rate of tilapia sac-fry carried a fitness advantage by reducing cadmium uptake under lethal stress. Therefore, post adapted physiological acclimation to one type of stress may carry a fitness advantage over metal stress. In all cases tolerance capability to metal stress was correlated to the metabolic status of yolk sac-fry. Using the most sensitive mouth brooder O niloticus and most tolerant substrate spawner T zillii which demonstrated the largest difference in their lethal tolerance to cadmium and copper, the effects of non-lethal cadmium stress were investigated. Significant differences in stress tolerance between the two species was observed. The effects of cadmium on growth and associated metabolic costs were similar for both species suggesting a general response under non-lethal cadmium stress. I here was evidence that both species showed an increase in protein turnover, and hence, an increase in maintenance metabolic costs. It was found that cadmium did not affect the energy supply, but reduced protein growth which appears to be due to investment of more supplied energy on increased protein turnover, and hence, increased maintenance metabolic cost than deposition as growth energy. Therefore, the predicted fitness advantage for lethal cadmium stress was observed for non-lethal cadmium stress. In conclusion, in tilapia yolk sac-fry there was a general response to lethal as well as non-lethal stress. The tolerance capability have been brought about either by genetically pre-determined or physiologically post-adapted variations in early life history traits of tilapia yolk sac-fry. The observed concordance between the range over which differences in responses occur in terms of more sensitive non-lethal stress indices and lethal tolerance capability of O. niloticus and T. zillii yolk sac-fry suggests there may be a possible link between responses to lethal and non-lethal cadmium stress

United Kingdom Terrestrial Evidence Partnership of Partnerships data products: improving opportunities for re-use

The United Kingdom Terrestrial Evidence Partnership of Partnerships (UKTEPoP) schemes produce a large quantity of data, both in terms of raw observations and results from analyses. UKTEPoP schemes produce ‘data products’ that have many commonalities which provides opportunities for analyses across schemes, creating greater value than if each scheme’s data were analysed in isolation. The FAIR principles of findability, accessibility, interoperability, and reusability were used to assess the current state of UKTEPoP data products and suggest opportunities for improvements that will lead to an increase in re-use

Dipropylamine for 9-Fluorenylmethyloxycarbonyl (Fmoc) Deprotection with Reduced Aspartimide Formation in Solid-Phase Peptide Synthesis.

Herein, we report dipropylamine (DPA) as a fluorenylmethyloxycarbonyl (Fmoc) deprotection reagent to strongly reduce aspartimide formation compared to piperidine (PPR) in high-temperature (60 °C) solid-phase peptide synthesis (SPPS). In contrast to PPR, DPA is readily available, inexpensive, low toxicity, and nonstench. DPA also provides good yields in SPPS of non-aspartimide-prone peptides and peptide dendrimers

Antioxidant Therapy Does Not Reduce Pain in Patients with Chronic Pancreatitis: The ANTICIPATE Study

Background & Aims: We investigated whether antioxidant therapy reduces pain and improves quality of life in patients with chronic pancreatitis. Methods: We performed a double-blind, randomized, controlled trial that compared the effects of antioxidant therapy with placebo in 70 patients with chronic pancreatitis. Patients provided 1 month of baseline data and were followed up for 6 months while receiving either Antox version 1.2 (Pharma Nord, Morpeth, UK) or matched placebo (2 tablets, 3 times/d). The primary analysis was baseline-adjusted change in pain score at 6 months, assessed by an 11-point numeric rating scale. Secondary analyses included alternative analyses of clinic and diary pain scores, scores on quality-of-life tests (the EORTC-QLQ-C30, QLQ-PAN28, EuroQOL EQ-5D, and EQ visual analog score), levels of antioxidants, use of opiates, and adverse events. Analyses, reported by intention to treat, were prospectively protocol-defined. Results: After 6 months, pain scores reported to the clinic were reduced by 1.97 from baseline in the placebo group and by 2.33 in the antioxidant group but were similar between groups (−0.36; 95% confidence interval, −1.44 to 0.72; P = .509). Average daily pain scores from diaries were also similar (3.05 for the placebo group, 2.93 for the antioxidant group, a difference of 0.11; 95% confidence interval, 1.05–0.82; P = .808). Measures of quality of life were similar between groups, as was opiate use and number of hospital admissions and outpatient visits. Blood levels of vitamin C and E, β-carotene, and selenium were increased significantly in the antioxidant group. Conclusi1ons: In patients with painful chronic pancreatitis of predominantly alcoholic origin, antioxidant therapy did not reduce pain or improve quality of life, despite causing a sustained increase in blood levels of antioxidants. Trial registration: ISRCTN-21047731

Landscape-scale responses of birds to agri-environment management: a test of the English Environmental Stewardship scheme

1. Agri-environment schemes (AES) are used extensively across Europe to address biodiversity declines in farmland. In England, Environmental Stewardship (ES) was introduced in 2005 to address the shortcomings of previous schemes, but as for schemes in other countries, assessments to date have revealed little evidence for national-scale biodiversity benefits. 2. Here, we assess the efficacy of ES in driving changes in national farmland bird populations over the period 2002–2010, using BTO/JNCC/RSPB Breeding Bird Survey data. We tested for associations between ES management options, grouped into categories reflecting intended biological effects (e.g. stubble), and species’ population growth rates, wherever benefits of management might be expected to occur. 3. We found strong evidence for positive effects of management that provides winter food resources (i.e. ES stubble and wild bird seed [WBS] crops) on population growth rates across multiple granivorous species, at three landscape scales. The results for management aiming to provide breeding season benefits (i.e. grassland, field margin and boundary [hedge, ditch] management) showed mixed patterns of positive and negative associations. 4. The results for stubble and WBS provide the first evidence for landscape-scale responses of biodiversity to AES management. The negative relationships identified may also show the importance of management context driving unforeseen predation or competition effects. 5. Synthesis and Applications. This study demonstrates that agri-environment scheme management has the potential to have national-scale effects on avian population growth rates, although our results suggest that some components of the scheme have had little effect on bird populations. Therefore, whilst this study provides the first proof-of-concept for broad-and-shallow scheme impacts on biodiversity, our results underline the importance of targeting towards population-limiting factors, here winter food resources. A combination of low uptake of key in-field options that provide winter seed and a failure to cover the late-winter period effectively explains the lack of national population responses. Such issues need to be addressed before schemes like Environmental Stewardship will achieve their goals. This study shows the value of feedback from monitoring for informing scheme design, through identifying problems and testing solutions

Performance of candidates declaring dyslexia in the MRCGP clinical skills assessment: cross sectional study

Introduction There are increasing numbers of doctors with dyslexia undertaking the MRCGP licensing exam for general practice. Exam bodies seek to be fair to candidates with disabilities such as dyslexia as part of their Public Sector Equality Duty under the Equality Act 2010. We aimed to investigate performance of doctors declaring dyslexia in the Clinical Skills Assessment (CSA) component of the MRCGP. Methods We used a cross-sectional design, analysing routine candidate performance and demographic data from the MRCGP CSA between 2010 and 2017. We used multivariable logistic regression to compare candidates who declared dyslexia (either ‘early’ before their first attempt, or ‘late’ after failing at least once) with candidates who did not declare dyslexia to investigate the effect of declaring dyslexia on passing the CSA taking into account number of attempts, sex, place of primary medical qualification and ethnicity. Results Overall, 20879 candidates took the CSA between 2010 and 2017 of which 598 (2.9%) declared dyslexia. Candidates declaring dyslexia were no different in ethnicity compared with those who did not declare dyslexia but were significantly more likely to be male (47.3 vs 37.8; p<0.001) and to have a non-UK primary medical qualification (27.0% vs 22.4%; p=0.001). Candidates who declared dyslexia late were significantly more likely to fail the CSA compared with those candidates who declared early (40.6% vs 9.2%; p<0.001). They were also more likely to have a non-UK medical qualification (79.3% vs 15.7%; p<0.001) or come from a minority ethnic group (84.9% vs 39.2%; p<0.001). Candidates who declared dyslexia were significantly less likely to pass the CSA compared to candidates who did not declare dyslexia, particularly when this was declared late (Incident Rate Ratio [IRR] 0.78, 95%; confidence interval [CI] 0.67 to 0.91) but also when declared early (IRR 0.94 95%; CI] 0.92 to 0.97). Conclusion Trainees declaring dyslexia, and particularly declared late, were less likely to pass the CSA. Differential attainment in doctors with dyslexia needs to be addressed by investigating potential causes and finding solutions for such disparities as well as facilitating earlier assessment of dyslexia in those not previously diagnosed, particularly ethnic minority non-UK trained doctors

Affordance-led framework of understanding of BIM adoption

Purpose Successful adoption of building information modelling (BIM) by early adopters is crucial for its effective diffusion. The purpose of this study is to develop a framework of understanding that supports contextualized understanding of BIM adoption decisions in a BIM infant industry. The framework bridges the gap in current knowledge in terms of the absence of such a framework, which has hindered the structured understanding of the BIM decision of an adopter, curtailing the appropriate strategizing of their BIM adoption. Design/methodology/approach The study focuses on a BIM infant industry, where early adopters begin using BIM, allowing insights into this crucial initial stage of adoption. Identifying affordances as a versatile concept that could effectively represent not only what an adopter perceives and expects from BIM implementation, but also, what the adopter, in fact, can achieve from it, an affordance-led framework of understanding (AFU) was developed to comprehensively capture varying dynamics of BIM decision process. The study took a qualitative retroductive approach to theory with semi-structured interviews to gather necessary data from a sample of BIM adopters purposively selected to maximize the breadth and depth of data. Findings The study concludes by identifying and defining pertinent affordances as a new concept and a compulsory state for BIM adoption. Findings further demonstrate that existing theories can be linked to the AFU to strategically direct the affordances dynamics towards the pertinent state. Originality/value The AFU enables a deeper contextualizable view of innovation adoption that was absent in existing innovation studies. It significantly enhances the precision of strategizing BIM adoption compared to previous approaches, enabling adopters to plan and implement BIM in a manner that aligns well with their expectations and specific conditions

VEGF-C is associated with lymphatic status and invasion in oral cancer

Background: Nodal metastasis is a major prognostic indicator for oral squamous cell carcinoma (OSCC) progression. Recently, it has been revealed that lymphangiogenic growth factor VEGF-C and its receptor Flt-4 play an important role for invasion and metastasis in cancer cells. Aim: To examine VEGF-C expression and its correlation with lymphatic status, including the number of lymph vessels and lymphatic invasion, tumour invasion and metastasis in OSCC. Methods: Intratumoural and peritumoural lymphatic vessels were examined using D2-40 in 54 OSCC cases and correlated with VEGF-C expression and clinicopathological findings. The histological pattern of invasion and pathological findings were compared. Results: High expression of VEGF-C was frequently observed in OSCC and was associated with increased number of lymph vessels and lymphatic invasion. VEGF-C was well correlated with invasion pattern and metastasis. Conclusions: Results suggest that VEGF-C may play an important role for lymphangiogenesis and invasion in the metastatic process and can be a strong predicting factor for metastasis of OSCC

Agarose microgel culture delineates lumenogenesis in naive and primed human pluripotent stem cells.

Human periimplantation development requires the transformation of the naive pluripotent epiblast into a polarized epithelium. Lumenogenesis plays a critical role in this process, as the epiblast undergoes rosette formation and lumen expansion to form the amniotic cavity. Here, we present a high-throughput in vitro model for epiblast morphogenesis. We established a microfluidic workflow to encapsulate human pluripotent stem cells (hPSCs) into monodisperse agarose microgels. Strikingly, hPSCs self-organized into polarized epiblast spheroids that could be maintained in self-renewing and differentiating conditions. Encapsulated primed hPSCs required Rho-associated kinase inhibition, in contrast to naive hPSCs. We applied microgel suspension culture to examine the lumen-forming capacity of hPSCs and reveal an increase in lumenogenesis during the naive-to-primed transition. Finally, we demonstrate the feasibility of co-encapsulating cell types across different lineages and species. Our work provides a foundation for stem cell-based embryo models to interrogate the critical components of human epiblast self-organization and morphogenesis