Experimental litterfall manipulation effects on soil bacterial community structure and soil carbon cycling in a wet tropical forest

Global changes such as increasing atmospheric carbon dioxide (CO2) concentrations or climate change are likely to drive shifts in plant-derived carbon (C) inputs to terrestrial ecosystems via changes in litterfall and plant net primary production (NPP). However, the effects of shifting detrital C inputs on belowground microbial community function, C cycling and fluxes remain largely unknown, especially in tropical forest ecosystems. To investigate how shifts in bacterial community composition resulting from differences in C availability affect organic matter decomposition and how soil C pools and fluxes respond to shifts in C inputs, I utilized an in situ litter manipulation experiment in a tropical rain forest in Costa Rica. In one study, I assessed whether changes in bacterial community composition and diversity were related to changes in microbial community function. To do this I used bar-coded pyrosequencing and a series of laboratory incubations to test the potential functional significance of community shifts on organic matter decomposition. In another study, I assessed the effects of the litterfall manipulation on in situ dissolved organic matter (DOM) fluxes, internal C and nutrient cycling, and soil CO2 fluxes. The manipulation had clear effects on soil bacterial community composition but mixed effects on microbial community function. These results show that while resource-driven shifts in soil bacterial community composition have the potential to influence decomposition of specific C substrates, those differences may not translate to differences in mixed DOM decomposition rates in situ. In the second study, results showed that increasing and decreasing litterfall inputs drove rapid and significant shifts in belowground C cycling, suggesting that shifts in litterfall inputs in response to global environmental change could have important consequences for belowground C storage and fluxes in tropical rain forests. Furthermore, the observed responses highlight the potential for marked differences between tropical ecosystems and temperate ecosystems, where the effects of forest litter on belowground C cycling are typically much more subtle. Taken together, these studies demonstrate the strong potential impacts of shifts in plant-derived C inputs on C cycling and bacterial community structure while having complex effects on microbial community function

Reducing Petroleum Consumption from Transportation

http://web.mit.edu/ceepr/www/publications/workingpapers.htmlThe United States consumed more petroleum-based liquid fuel per capita than any other OECD- high-income country- 30 percent more than the second-highest country (Canada) and 40 percent more than the third-highest (Luxemburg). This paper examines the main channels through which reductions in U.S. oil consumption might take place: (a) increased fuel economy of existing vehicles, (b) increased use of non-petroleum-based low-carbon fuels, (c) alternatives to the internal combustion engine, and (d) reduced vehicles miles travelled. I then discuss how the policies for reducing petroleum consumption used in the US compare with the standard economics prescription for using a Pigouvian tax to deal with externalities. Taking into account that energy taxes are a political hot button in the United States, and also considering some evidence that consumers may not correctly value fuel economy, I offer some thoughts about the margins on which policy aimed at reducing petroleum consumption might usefully proceed

Doctoral Recital

List of performers and performances

Cardiovascular Pathophysiology in Chronic Kidney Disease: Opportunities to Transition from Disease to Health

Background: Chronic kidney disease (CKD) is common, and is associated with a high burden of cardiovascular disease. This cardiovascular risk is incompletely explained by traditional risk factors, calling attention to a need to better understand the pathways in CKD contributing to adverse cardiovascular outcomes. Findings: Pathophysiological derangements associated with CKD, including disordered sodium, potassium, and water homeostasis, renin-angiotensin-aldosterone and sympathetic activity, anemia, bone and mineral metabolism, uremia, and toxin accumulation may contribute directly to progression of cardiovascular disease and adverse outcomes. Conclusion: Improving cardiovascular health in patients with CKD requires improved understanding of renocardiac pathophysiology. Ultimately, the most successful strategy may be prevention of incident CKD itself

Three Cases of COVID-19 Pneumonia That Responded to Icosapent Ethyl Supportive Treatment

BACKGROUND Icosapent ethyl, a form of eicosapentaenoic acid with anti-inflammatory activity, has been approved as an adjunctive treatment with statins in patients with hypertriglyceridemia. Icosapent ethyl is currently undergoing clinical trials to determine its anti-inflammatory effects in patients with coronavirus disease 2019 (COVID-19). This report describes 3 intensive care unit (ICU) patients with moderate to severe COVID-19 pneumonia treated with icosapent ethyl as part of their supportive care who had favorable outcomes. CASE REPORT Case 1 was a 75-year-old man with a past medical history of hyperlipidemia, hypertension, type 2 diabetes mellitus, obesity, and benign prostatic hyperplasia. Case 2 was a 23-year old man with a past medical history of type 2 diabetes mellitus and obesity. Case 3 was a 24-year old man with a history of autism. All cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection were confirmed from a nasopharyngeal swab using the Becton Dickinson nasopharyngeal reverse-transcription polymerase chain reaction. All patients in these cases were treated with a course of 2 g of icosapent ethyl twice a day by nasogastric tube. CONCLUSIONS This report of 3 cases describes the use of icosapent ethyl as a component of supportive treatments in ICU patients with moderate to severe COVID-19 pneumonia. However, as of yet there are no evidence-based treatments for SARS-CoV-2 infection from controlled clinical trials. The outcomes of ongoing clinical trials are awaited to determine whether icosapent ethyl has anti-inflammatory effects in patients with SARS-CoV-2 infection and which patients might benefit from the use of this adjunctive treatment

High impact exercise increased femoral neck bone mineral density in older men: a randomised unilateral intervention

Introduction: There is little evidence as towhether exercise can increase BMD in oldermenwith no investigation of high impact exercise. Lifestyle changes and individual variability may confound exercise trials but can be minimised using a within-subject unilateral design (exercise leg [EL] vs. control leg [CL]) that has high statistical power. Purpose: This study investigated the influence of a 12 month high impact unilateral exercise intervention on femoral neck BMD in older men. Methods: Fifty, healthy, community-dwelling older men commenced a 12 month high impact unilateral exercise intervention which increased to 50 multidirectional hops, 7 days a week on one randomly allocated leg. BMD of both femurswasmeasured using dual energy X-ray absorptiometry (DXA) before and after 12 months of exercise, by an observer blind to the leg allocation. Repeated measures ANOVAwith post hoc tests was used to detect significant effects of time, leg and interaction. Results: Thirty-five men (mean±SD, age 69.9±4.0 years) exercised for 12 months and intervention adherence was 90.5±9.1% (304±31 sessions completed out of 336 prescribed sessions). Fourteen men did not complete the 12 month exercise intervention due to: health problems or injuries unrelated to the intervention (n=9), time commitments (n=2), or discomfort during exercise (n=3), whilst BMD data were missing for one man. Femoral neck BMD, BMC and cross-sectional area all increased in the EL (+0.7, +0.9 and +1.2 % respectively) compared to the CL (−0.9,−0.4 and −1.2%); interaction effect Pb0.05. Although the interaction term was not significant (P>0.05), there were significantmain effects of time for sectionmodulus (P=0.044) and minimum neck width (P=0.006). Sectionmodulus increased significantly in the EL (P=0.016) but not in the CL (P=0.465); mean change+2.3% and+0.7% respectively, whereasminimumneck width increased significantly in the CL (P=0.004) but not in the EL (P=0.166); mean changes being +0.7% and +0.3% respectively. Conclusion: A 12 month high impact unilateral exercise intervention was feasible and effective for improving femoral neck BMD, BMC and geometry in older men. Carefully targeted high impact exercises may be suitable for incorporation into exercise interventions aimed at preventing fractures in healthy community-dwelling older men

Changes in functional connectivity in people with HIV switching antiretroviral therapy

We assessed changes in functional connectivity by fMRI (functional magnetic resonance imaging) and cognitive measures in otherwise neurologically asymptomatic people with HIV (PWH) switching combination antiretroviral therapy (cART). In a prospective study (baseline and follow-up after at least 4 months), virologically suppressed PWH switched non-nuclease reverse-transcriptase inhibitors (NNRTI; tenofovir-DF/emtricitabine with efavirenz to rilpivirine) and integrase-strand-transfer inhibitors (INSTI; tenofovir-DF/emtricitabine with raltegravir to dolutegravir). PWH were assessed by resting-state fMRI and stop-signal reaction time (SSRT) task fMRI as well as with a cognitive battery (CogState™) at baseline and follow-up. Switching from efavirenz to rilpivirine (n = 10) was associated with increased functional connectivity in the dorsal attention network (DAN) and a reduction in SSRTs (p = 0.025) that positively correlated with the time previously on efavirenz (mean = 4.8 years, p = 0.02). Switching from raltegravir to dolutegravir (n = 12) was associated with increased connectivity in the left DAN and bilateral sensory-motor and associative visual networks. In the NNRTI study, significant improvements in the cognitive domains of executive function, working memory and speed of visual processing were observed, whereas no significant changes in cognitive function were observed in the INSTI study. Changes in fMRI are evident in PWH without perceived neuropsychiatric complaints switching cART. fMRI may be a useful tool in assisting to elucidate the underlying pathogenic mechanisms of cART-related neuropsychiatric effects

Elevated Levels of IL-10 and G-CSF Associated with Asymptomatic Malaria in Pregnant Women

In sub-Saharan Africa, approximately 30 million pregnant women are at risk of contracting malaria annually. Nearly 36% of healthy pregnant women receiving routine antenatal care tested positive for Plasmodium falciparum HRP-II antigen in Ghana. We tested the hypothesis that asymptomatic HRP II positive pregnant women expressed a unique Th1 and Th2 phenotype that differs from healthy controls. Plasma from healthy (n = 15) and asymptomatic (n = 25) pregnant women were evaluated for 27 biomarkers (IL-1b, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-12, IL-13, IL-15, IL- 17, Eotaxin, bFGF-2, G-CSF, GM-CSF, IFN-γ, IP-10, MCP-1, MIP-1α, MIP-1β, PDGF-bb, RANTES, TNF, and VEGF) associated with Th1 and Th2 cytokine homeostasis. IL-10 and G-CSF levels were elevated in the asymptomatic group when compared with the healthy group (P = .031 and .041, resp.). The median ratios of IL-1β:5, IL-1β:10, IL-1β:G-CSF, IL-1β:Eotaxin, IL-12:G-CSF, IL-15:10, IL-17:G-CSF, IL-17:Eotaxin, TNF:IL-4, TNF:IL-5, and TNF:G-CSF were significantly different among the two groups. Thus, asymptomatic malaria carriage may be linked to circulating levels of IL-10 and G-CSF

A comprehensive promoter landscape identifies a novel promoter for CD133 in restricted tissues, cancers, and stem cells

PROM1 is the gene encoding prominin-1 or CD133, an important cell surface marker for the isolation of both normal and cancer stem cells. PROM1 transcripts initiate at a range of transcription start sites (TSS) associated with distinct tissue and cancer expression profiles. Using high resolution Cap Analysis of Gene Expression (CAGE) sequencing we characterize TSS utilization across a broad range of normal and developmental tissues. We identify a novel proximal promoter (P6) within CD133+ melanoma cell lines and stem cells. Additional exon array sampling finds P6 to be active in populations enriched for mesenchyme, neural stem cells and within CD133+ enriched Ewing sarcomas. The P6 promoter is enriched with respect to previously characterized PROM1 promoters for a HMGI/Y (HMGA1) family transcription factor binding site motif and exhibits different epigenetic modifications relative to the canonical promoter region of PROM1

The Influence of High-Impact Exercise on Cortical and Trabecular Bone Mineral Content and 3D Distribution Across the Proximal Femur in Older Men: A Randomized Controlled Unilateral Intervention.

Regular exercisers have lower fracture risk, despite modest effects of exercise on bone mineral content (BMC). Exercise may produce localized cortical and trabecular bone changes that affect bone strength independently of BMC. We previously demonstrated that brief, daily unilateral hopping exercises increased femoral neck BMC in the exercise leg versus the control leg of older men. This study evaluated the effects of these exercises on cortical and trabecular bone and its 3D distribution across the proximal femur, using clinical CT. Fifty healthy men had pelvic CT scans before and after the exercise intervention. We used hip QCT analysis to quantify BMC in traditional regions of interest and estimate biomechanical variables. Cortical bone mapping localized cortical mass surface density and endocortical trabecular density changes across each proximal femur, which involved registration to a canonical proximal femur model. Following statistical parametric mapping, we visualized and quantified statistically significant changes of variables over time in both legs, and significant differences between legs. Thirty-four men aged mean (SD) 70 (4) years exercised for 12-months, attending 92% of prescribed sessions. In traditional regions of interest, cortical and trabecular BMC increased over time in both legs. Cortical BMC at the trochanter increased more in the exercise than control leg, whereas femoral neck buckling ratio declined more in the exercise than control leg. Across the entire proximal femur, cortical mass surface density increased significantly with exercise (2.7%; p 6%) at anterior and posterior aspects of the femoral neck and anterior shaft. Endocortical trabecular density also increased (6.4%; p 12% at the anterior femoral neck, trochanter, and inferior femoral head. Odd impact exercise increased cortical mass surface density and endocortical trabecular density, at regions that may be important to structural integrity. These exercise-induced changes were localized rather than being evenly distributed across the proximal femur.This research was financially supported by a National Osteoporosis Innovative Award, Medical Research Council UK Interdisciplinary Bridging Award, and a Loughborough University Scholarship. KESP acknowledges support of the Cambridge NIHR Biomedical Research Centre.This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/jbmr.249