Towards a community of Open Research Champions: insight from the Cambridge Data Champion Programme

This presentation is for “FAIR Science: tricky problems and creative solutions”, which took place at the Wellcome Auditorium, The Queen’s Medical Research Institute, University of Edinburgh. This one day event is organised by Ralitsa Madsen

Consumer Panel—Judicial Estoppel: Its Development, Current Status, and How the Eleventh Circuit\u27s Forthcoming Opinion in Slater Might Portend the End of its Rigidity

The Consumer Panel presented a history of the doctrine of judicial estoppel, how it applies in bankruptcy, and offered insights about the doctrine\u27s viability in bankruptcy

Cover crops affect the partial nitrogen balance in a maize-forage cropping system

Part of the nitrogen (N) fertilizer applied to crops is lost to the environment, contributing to global warming, eutrophication, and groundwater contamination. However, low N supply stimulates soil organic N turnover and carbon (C) loss, since the soil N/C ratio in soil is quasi-constant, ultimately resulting in land degradation. Grasses such as ruzigrass (Urochloa ruziziensis) grown as winter pasture or a cover crop in rotation with maize (Zea mays) can reduce N leaching, however, this may induce N deficiency and depress yields in the subsequent maize crop. Despite the potential to decrease N loss, this rotation may negatively affect the overall N balance of the cropping system. However, this remains poorly quantified. To test this hypothesis, maize, fertilized with zero to 210 kg N ha−1, was grown after ruzigrass, palisade grass (Urochloa brizanta) and Guinea grass (Pannicum maximum), and the N inputs, outputs and partial N balance determined. Despite the intrinsically poor soil quality associated with the tropical Ultisol, maize grown after the grasses was efficient in acquiring N, resulting in a negative N balance even when 210 kg ha−1 of N was applied after Guinea grass. Losses by leaching, N2O emission and NH3 volatilization did not exceed 13.8 kg ha−1 irrespective of the grass type. Despite a similar N loss among grasses, Guinea grass resulted in a higher N export in the maize grain due to a higher yield, resulting in a more negative N balance. Soil N depletion can lead to C loss, which can result in land degradation

Shifts in Soil Structure, Biological, and Functional Diversity Under Long-Term Carbon Deprivation

Soil organic matter is composed of a variety of carbon (C) forms. However, not all forms are equally accessible to soil microorganisms. Deprivation of C inputs will cause changes in the physical and microbial community structures of soils; yet the trajectories of such changes are not clear. We assessed microbial communities using phospholipid fatty acid profiling, metabarcoding, CO2 emissions, and functional gene microarrays in a decade-long C deprivation field experiment. We also assessed changes in a range of soil physicochemical properties, including using X-ray Computed Tomography imaging to assess differences in soil structure. Two sets of soils were deprived of C inputs by removing plant inputs for 10 years and 1 year, respectively. We found a reduction in diversity measures, after 10 years of C deprivation, which was unexpected based on previous research. Fungi appeared to be most impacted, likely due to competition for scarce resources after exhausting the available plant material. This suggestion was supported by evidence of bioindicator taxa in non-vegetated soils that may directly compete with or consume fungi. There was also a reduction in copies of most functional genes after 10 years of C deprivation, though gene copies increased for phytase and some genes involved in decomposing recalcitrant C and methanogenesis. Additionally, soils under C deprivation displayed expected reductions in pH, organic C, nitrogen, and biomass as well as reduced mean pore size, especially in larger pores. However, pore connectivity increased after 10 years of C deprivation contrary to expectations. Our results highlight concurrent collapse of soil structure and biodiversity following long-term C deprivation. Overall, this study shows the negative trajectory of continuous C deprivation and loss of organic matter on a wide range of soil quality indicators and microorganisms

Vasopressin in conjunction with norepinephrine in septic shock: A retrospective cohort study from a low middle-income country

Objectives: Guidelines recommend use of norepinephrine as the first-line treatment for fluid-refractory septic shock and if septic shock persists vasopressin may be initiated. Since there are limited data from low middle-income countries with high disease burden of sepsis, we aimed to compare the outcomes of using vasopressin adjunct to norepinephrine in comparison with norepinephrine alone.Design: Retrospective cohort study.Setting: Aga Khan University Hospital, Karachi, Pakistan.Patients: Six-hundred fifty-three patients diagnosed with septic shock from January 2019 to December 2019, with 498 given norepinephrine only and 155 given norepinephrine-vasopressin combination.Interventions: None.Measurements and main results: Primary outcome was in-hospital mortality. Secondary outcomes were duration of vasopressor used, length of hospital stay, length of ICU stay, and days on ventilatory support. After adjustment by multivariable logistic regression, it was found that mortality was not significantly associated with the norepinephrine-vasopressin combination (adjusted odds ratio, 0.633 [95% CI, 0.370-1.081]). However, Sequential Organ Failure Assessment score at admission (1.100 [1.014-1.193]), lactate at admission (1.167 [1.109-1.227]), duration of vasopressor used (1.481 [1.316-1.666]), and level of care (3.025 [1.682-5.441]) were found to be independently associated with the adjunct usage of norepinephrine and vasopressin.Conclusions: The use of norepinephrine-vasopressin combination has remained debatable in literature. Our study showed that although there was no difference in mortality between the two groups, admission Sequential Organ Failure Assessment scores and admission lactate levels were found to be significantly higher in the norepinephrine-vasopressin group. Hence, physicians from Pakistan used the norepinephrine-vasopressin combination in resistant septic shock patients who were sicker to begin with. Furthermore, duration of vasopressor therapy and ICU admission were also significantly higher in the combination group. Considering the recent hyperinflation of vasopressors costs and that most healthcare expenditure for patients in Pakistan is out-of-pocket, this can consequently lead to unwarranted financial burden for patients and their families

Susceptibility to hormone-mediated cancer is reflected by different tick rates of the epithelial and general epigenetic clock

Background A variety of epigenetic clocks utilizing DNA methylation changes have been developed; these clocks are either tissue-independent or designed to predict chronological age based on blood or saliva samples. Whether discordant tick rates between tissue-specific and general epigenetic clocks play a role in health and disease has not yet been explored. Results Here we analyze 1941 cervical cytology samples, which contain a mixture of hormone-sensitive cervical epithelial cells and immune cells, and develop the WID general clock (Women’s IDentification of risk), an epigenetic clock that is shared by epithelial and immune cells and optimized for cervical samples. We then develop the WID epithelial clock and WID immune clock, which define epithelial- and immune-specific clocks, respectively. We find that the WID-relative-epithelial-age (WID-REA), defined as the difference between the epithelial and general clocks, is significantly reduced in cervical samples from pre-menopausal women with breast cancer (OR 2.7, 95% CI 1.28-5.72). We find the same effect in normal breast tissue samples from pre-menopausal women at high risk of breast cancer and show that potential risk reducing anti-progesterone drugs can reverse this. In post-menopausal women, this directionality is reversed. Hormone replacement therapy consistently leads to a significantly lower WID-REA in cancer-free women, but not in post-menopausal women with breast or ovarian cancer. Conclusions Our findings imply that there are multiple epigenetic clocks, many of which are tissue-specific, and that the differential tick rate between these clocks may be an informative surrogate measure of disease risk.publishedVersio

Life at the extreme: Plant-driven hotspots of soil nutrient cycling in the hyper-arid core of the Atacama Desert

The hyperarid core of the Atacama Desert represents one of the most intense environments on Earth, often being used as an analog for Mars regolith. The area is characterized by extremes in climate (e.g., temperature, humidity, UV irradiation) and edaphic factors (e.g., hyper-salinity, high pH, compaction, high perchlorates, and low moisture, phosphorus and organic matter). However, the halophytic C4 plant Distichlis spicata appears to be one of the few species on the planet that can thrive in this environment. Within this habitat it captures windblown sand leading to the formation of unique structures and the generation of above-ground phyllosphere soil. Using a combination of approaches (e.g., X-ray Computed Tomography, TXRF, δ13C/δ15N isotope profiling, microbial PLFAs, 14C turnover, phosphate sorption isotherms) we examined the factors regulating the biogeochemical cycling of nitrogen (N), phosphorus (P) and carbon (C) in both vegetated and unvegetated areas. Our results showed that D. spicata rhizomes with large aerenchyma were able to break through the highly cemented topsoil layer leading to root proliferation in the underlying soil. The presence of roots increased soil water content, P availability and induced a change in microbial community structure and promoted microbial growth and activity. In contrast, soil in the phyllosphere exhibited almost no biological activity. Organic C stocks and recent C4 plant derived input increased as follows: phyllosphere (1941 g C m−2; 85% recent) > soils under plants (575–748 g C m−2; 55–60%) > bare soils (491–642 g C m−2; 9–17%). Due to the high levels of nitrate in soil (>2 t ha−1) and high rates of P sorption/precipitation, our data suggest that the microbial activity is both C and P, but not N limited. Root-mediated salt uptake combined with foliar excretion and dispersal of NaCl into the surrounding area indicated that D. spicata was responsible for actively removing ca. 55% of the salt from the rhizosphere. We also demonstrate that NH3 emissions may represent a major N loss pathway from these soil ecosystems during the processing of organic N. We attribute this to NH3 volatilization to the high pH of the soil and slow rates of nitrification. In conclusion, we demonstrate that the extremophile D. spicata physically, chemically and biologically reengineers the soil to create a highly bioactive hotspot within the climate-extreme of the Atacama Desert

Antiprogestins reduce epigenetic field cancerization in breast tissue of young healthy women

Background: Breast cancer is a leading cause of death in premenopausal women. Progesterone drives expansion of luminal progenitor cells, leading to the development of poor-prognostic breast cancers. However, it is not known if antagonising progesterone can prevent breast cancers in humans. We suggest that targeting progesterone signalling could be a means of reducing features which are known to promote breast cancer formation. Methods: In healthy premenopausal women with and without a BRCA mutation we studied (i) estrogen and progesterone levels in saliva over an entire menstrual cycle (n = 20); (ii) cancer-free normal breast-tissue from a control population who had no family or personal history of breast cancer and equivalently from BRCA1/2 mutation carriers (n = 28); triple negative breast cancer (TNBC) biopsies and healthy breast tissue taken from sites surrounding the TNBC in the same individuals (n = 14); and biopsies of ER+ve/PR+ve stage T1–T2 cancers and healthy breast tissue taken from sites surrounding the cancer in the same individuals (n = 31); and (iii) DNA methylation and DNA mutations in normal breast tissue (before and after treatment) from clinical trials that assessed the potential preventative effects of vitamins and antiprogestins (mifepristone and ulipristal acetate; n = 44). Results: Daily levels of progesterone were higher throughout the menstrual cycle of BRCA1/2 mutation carriers, raising the prospect of targeting progesterone signalling as a means of cancer risk reduction in this population. Furthermore, breast field cancerization DNA methylation signatures reflective of (i) the mitotic age of normal breast epithelium and (ii) the proportion of luminal progenitor cells were increased in breast cancers, indicating that luminal progenitor cells with elevated replicative age are more prone to malignant transformation. The progesterone receptor antagonist mifepristone reduced both the mitotic age and the proportion of luminal progenitor cells in normal breast tissue of all control women and in 64% of BRCA1/2 mutation carriers. These findings were validated by an alternate progesterone receptor antagonist, ulipristal acetate, which yielded similar results. Importantly, mifepristone reduced both the TP53 mutation frequency as well as the number of TP53 mutations in mitotic-age-responders. Conclusions: These data support the potential usage of antiprogestins for primary prevention of poor-prognostic breast cancers

New insights into the classification and nomenclature of cortical GABAergic interneurons.

A systematic classification and accepted nomenclature of neuron types is much needed but is currently lacking. This article describes a possible taxonomical solution for classifying GABAergic interneurons of the cerebral cortex based on a novel, web-based interactive system that allows experts to classify neurons with pre-determined criteria. Using Bayesian analysis and clustering algorithms on the resulting data, we investigated the suitability of several anatomical terms and neuron names for cortical GABAergic interneurons. Moreover, we show that supervised classification models could automatically categorize interneurons in agreement with experts' assignments. These results demonstrate a practical and objective approach to the naming, characterization and classification of neurons based on community consensus