Regulation of the Base Excision Repair Pathway by Ubiquitination

Genome integrity is under constant threat from cellular reactive oxygen species generated by endogenous and exogenous mutagens. The base excision repair (BER) pathway consequently plays a crucial role in the repair of DNA base damage, sites of base loss and DNA single strand breaks that can cause genome instability and ultimately the development of human diseases, including premature ageing, neurodegenerative disorders and cancer. Proteins within the base excision repair pathway are increasingly being found to be regulated and controlled by post-translational modifications, and indeed ubiquitination performs a key role in the maintenance of repair protein levels but may also impact on protein activity and cellular localisation. This process is therefore important in maintaining an efficient cellular DNA damage response, and if not accurately controlled, can cause DNA damage accumulation and promote mutagenesis and genomic instability. In this chapter, we will present up-to-date information on the evidence of ubiquitination of base excision repair proteins, the enzymes involved and the molecular and cellular consequences of this process

Elevated pCO2 enhances bacterioplankton removal of organic carbon.

Factors that affect the removal of organic carbon by heterotrophic bacterioplankton can impact the rate and magnitude of organic carbon loss in the ocean through the conversion of a portion of consumed organic carbon to CO2. Through enhanced rates of consumption, surface bacterioplankton communities can also reduce the amount of dissolved organic carbon (DOC) available for export from the surface ocean. The present study investigated the direct effects of elevated pCO2 on bacterioplankton removal of several forms of DOC ranging from glucose to complex phytoplankton exudate and lysate, and naturally occurring DOC. Elevated pCO2 (1000-1500 ppm) enhanced both the rate and magnitude of organic carbon removal by bacterioplankton communities compared to low (pre-industrial and ambient) pCO2 (250 -~400 ppm). The increased removal was largely due to enhanced respiration, rather than enhanced production of bacterioplankton biomass. The results suggest that elevated pCO2 can increase DOC consumption and decrease bacterioplankton growth efficiency, ultimately decreasing the amount of DOC available for vertical export and increasing the production of CO2 in the surface ocean

Value priorities of people with mental health problems and the relationship between value discrepancies and distress

Introduction: Values have a strong tradition in social psychology, but until recently they have been largely neglected in mental health literature. More recently, the importance of values has been recognised by some psychological therapies (e.g. Acceptance and Commitment Therapy); however, the relative importance of values in mental health problems has not been empirically tested. Aims: The current research aimed to investigate the value priorities of people with anxiety and eating disorders, and to assess the relationship between value discrepancies and distress, and in doing so to draw upon Schwartz’s (1992) model of values and Higgins’s (1987) self-discrepancy theory. More specifically, it investigated whether people with anxiety and eating disorders differ from people without mental health problems in the values that they hold, and the level of value discrepancies in these values, and additionally whether these discrepancies were associated with anxiety and depression. Methods: A cross-sectional questionnaire-based design was employed, with data being collected from 122 participants (an anxiety disorder group, n=30; eating disorder group, n=31; and reference group n=61). Multivariate statistics, paired sample t-tests and Pearson’s correlations were used to test the hypotheses. All participants completed a measure assessing values and discrepancies in values (adapted PVQ), and the mental health groups also completed a measure assessing psychological distress (HADS). Results: The reference group rated particular values (e.g. self-direction, stimulation, hedonism) as more important than did the mental health groups, apart from the achievement value, which the eating disorders group rated as more important. The mental health groups had higher value discrepancies than the reference group. Actual-Ideal and Actual-Ought value discrepancies were found to be related to anxiety and depression. However, unexpectedly, depression was found not to be specifically associated with Actual-Ideal discrepancies and anxiety was found not to be specifically associated with Actual-Ought discrepancies. Conclusions: This study provides empirical support and evidence for considering the values that people with mental health problems hold and the role that values has in relation to the psychological distress experienced by people. The results are discussed with reference to existing literature and the strength and limitations of the research were outlined. In addition, the clinical limitations were discussed and ideas for future research were outlined

Multifaceted impacts of the stony coral Porites astreoides on picoplankton abundance and community composition

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Limnology and Oceanography 62 (2017): 217–234, doi:10.1002/lno.10389.Picoplankton foster essential recycling of nutrients in the oligotrophic waters sustaining coral reef ecosystems. Despite this fact, there is a paucity of data on how the specific interactions between corals and planktonic bacteria and archaea (picoplankton) contribute to nutrient dynamics and reef productivity. Here, we utilized mesocosm experiments to investigate how corals and coral mucus influence picoplankton and nutrients in reef waters. Over 12 days, we tracked nutrient concentrations, picoplankton abundances and taxonomic composition of picoplankton using direct cell-counts, sequencing of SSU rRNA genes and fluorescent in situ hybridization-based abundances of dominant lineages in the presence or absence of Porites astreoides corals and with mucus additions. Our results demonstrate that when corals are present, Synechococcus, SAR11 and Rhodobacteraceae cells are preferentially removed. When corals were removed, their exudates enhanced the growth of diverse picoplankton, including SAR11 and Rhodobacteraceae. A seven-fold increase in nitrate concentration, possibly caused by nitrogen remineralization (ammonification coupled to nitrification) within the coral holobiont, may have further facilitated the growth of these taxa. In contrast, the addition of mucus resulted in rapid initial growth of total picoplankton and Rhodobacteraceae, but no measurable change in overall community structure. This study presents evidence of the multifaceted influences of corals on picoplankton, in which the coral holobiont selectively removes and promotes the growth of diverse picoplankton and remineralizes nitrogen.NSF Grant Number: OCE-1233612; NSF Oceanic Microbial Observatory Grant Number: OCE-080199

C. elegans Positive Butanone Learning, Short-term, and Long-term Associative Memory Assays

The memory of experiences and learned information is critical for organisms to make choices that aid their survival. C. elegans navigates its environment through neuron-specific detection of food and chemical odors1, 2, and can associate nutritive states with chemical odors3, temperature4, and the pathogenicity of a food source5

Retaining the general practitioner workforce in England : what matters to GPs? A cross-sectional study

Background: The general practice (GP) workforce in England is in crisis, reflected in increasing rates of early retirement and intentions to reduce hours of working. This study aimed to investigate underlying factors and how these might be mitigated. Methods: GPs in central England were invited to participate in an on-line survey exploring career plans and views and experiences of work-related pressures. Quantitative data were analysed using logistic regression analysis and principal components analysis. Qualitative data were analysed using a thematic framework approach. Results: Of 1,192 GPs who participated, 978 (82.0 %) stated that they intend to leave general practice, take a career break and/or reduce clinical hours of work within the next five years. This included 488 (41.9 %) who intend to leave practice, and almost a quarter (279; 23.2 %) intending to take a career break. Only 67 (5.6 %) planned to increase their hours of clinical work. For participants planning to leave practice, the issues that most influenced intentions were volume and intensity of workload, time spent on “unimportant tasks”, introduction of seven-day working and lack of job satisfaction. Four hundred fifty five participants responded to open questions (39128 words in total). The main themes were the cumulative impact of work-related pressures, the changing and growing nature of the workload, and the consequent stress. Reducing workload intensity, workload volume, administrative activities, with increased time for patient care, no out-of-hour commitments, more flexible working conditions and greater clinical autonomy were identified as the most important requirements to address the workforce crisis. In addition, incentive payments, increased pay and protected time for education and training were also rated as important. Conclusions: New models of professionalism and organisational arrangements may be needed to address the issues described here. Without urgent action, the GP workforce crisis in England seems set to worsen

Different carboxyl-rich alicyclic molecules proxy compounds select distinct bacterioplankton for oxidation of dissolved organic matter in the mesopelagic Sargasso Sea

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Liu, S., Parsons, R., Opalk, K., Baetge, N., Giovannoni, S., Bolanos, L. M., Kujawinski, E. B., Longnecker, K., Lu, Y., Halewood, E., & Carlson, C. A. Different carboxyl-rich alicyclic molecules proxy compounds select distinct bacterioplankton for oxidation of dissolved organic matter in the mesopelagic Sargasso Sea. Limnology and Oceanography, (2020), doi:10.1002/lno.11405.Marine dissolved organic matter (DOM) varies in its recalcitrance to rapid microbial degradation. DOM of varying recalcitrance can be exported from the ocean surface to depth by subduction or convective mixing and oxidized over months to decades in deeper seawater. Carboxyl‐rich alicyclic molecules (CRAM) are characterized as a major component of recalcitrant DOM throughout the oceanic water column. The oxidation of CRAM‐like compounds may depend on specific bacterioplankton lineages with oxidative enzymes capable of catabolizing complex molecular structures like long‐chain aliphatics, cyclic alkanes, and carboxylic acids. To investigate the interaction between bacteria and CRAM‐like compounds, we conducted microbial remineralization experiments using several compounds rich in carboxyl groups and/or alicyclic rings, including deoxycholate, humic acid, lignin, and benzoic acid, as proxies for CRAM. Mesopelagic seawater (200 m) from the northwest Sargasso Sea was used as media and inoculum and incubated over 28 d. All amendments demonstrated significant DOC removal (2–11 μmol C L−1) compared to controls. Bacterioplankton abundance increased significantly in the deoxycholate and benzoic acid treatments relative to controls, with fast‐growing Spongiibacteracea, Euryarcheaota, and slow‐growing SAR11 enriched in the deoxycholate treatment and fast‐growing Alteromonas, Euryarcheaota, and Thaumarcheaota enriched in the benzoic acid treatment. In contrast, bacterioplankton grew slower in the lignin and humic acid treatments, with oligotrophic SAR202 becoming significantly enriched in the lignin treatment. Our results indicate that the character of the CRAM proxy compounds resulted in distinct bacterioplankton removal rates of DOM and affected specific lineages of bacterioplankton capable of responding.We thank Z. Landry for the inspiring idea of SAR202 catabolism of CRAM. We thank the University of California, Santa Barbara Marine Science Institute Analytical Laboratory for analyzing inorganic nutrient samples. We thank C. Johnson for her help in FISH sample processing and BATS group in supporting our project. We thank N. K. Rubin‐Saika and R. Padula for their help with amino acid sample preparation. We thank Z. Liu, J. Xue, K. Lu, and Y. Shen for their help with amino acid protocol development and validation. We thank B. Stephens for his help on microscopic image analysis. We thank M. Dasenko and the staff of the CGRB at Oregon State University for amplicon library preparation and DNA sequencing. We are grateful for the help provided by the officers and crews of the R/V Atlantic Explorer. Bermuda Institute of Ocean Sciences (BIOS) provides us tremendous support in terms of facilities and lab space. We thank Bermuda government for its allowance of our water sampling and sample export (export permit number SP160904, issued 07 October 2016 under the Fisheries Act, 1972). This project was supported by Simons Foundation International's BIOS‐SCOPE program