A limited understanding of the potential to reduce emissions and a lack of climate incentives hinder progress toward mitigating greenhouse gas (GHG) emissions from beef production. This study explored the GHG mitigation potential in South America by evaluating nearly 30 beef cattle production systems across five key beef-producing countries (Argentina, Brazil, Colombia, Paraguay, and Uruguay). The study outlined a low-emission beef roadmap for this major beef producing region. Data from this study indicate that the current business-as-usual trajectory of improvements in South America's beef cattle production is insufficient to reduce GHG emissions at a pace that aligns with the urgency of climate crisis. Results from this study show that scaling up existing practices -such as improved forages, rotational grazing, and feed supplementation- to match the performance of the region's lowest-emission systems at 20thpercentile could deliver significant results. Emission intensities could decrease by 33-50% compared to the projected 2050 regional average (35 tons carbon dioxide equivalent/ton of carcass weight). This would flatten the emissions curve, cutting total emissions by 20-40% while simultaneously increasing beef production by 43%. With annual methane (CH4) emission reductions by 1.5%, the warming effect could decrease by 70-90%, offering a transformative pathway to lower GHG emissions from beef production. This emissions trajectory offers a feasible path toward net-zero warming from beef production, primarily through sustained reductions in CH4 emissions intensity and absolute emissions as systems become more production efficient. These findings highlight the need and an opportunity for a drastic reduction in emissions from beef cattle production and can foster collaboration among conservation, industry, and finance stakeholders towards a common climate-oriented beef production agenda.

Intermittent irrigation is widely recognized for potentially reducing global methane (CH4) emissions from flooded rice systems. In many regions, including parts of Asia and Latin America, applying inorganic fertilizers and choosing fertilizer types are vital strategies to mitigate nitrous oxide (N2O) emissions by controlling soil moisture. These practices have been increasingly adopted as part of sustainable rice cultivation methods aimed at reducing greenhouse gas emissions. However, despite their effectiveness, adoption of such practices remains limited in several rice-growing areas, particularly in developing regions. Consequently, the comprehensive effects of intermittent irrigation on CH4 and N2O emissions and rice grain yield require further investigation to understand their global implications fully. The objectives of this study were to examine the differential impacts of water management strategies, specifically intermittent irrigation versus flooded irrigation, on greenhouse gas emissions in two rice-growing regions in Colombia: Tolima and Casanare. Our analysis includes methane (CH4) and nitrous oxide (N2O) emissions, global warming potential (GWP), and crop yields using randomized block designs for commercial rice varieties. The results demonstrate that transitioning from flooding to intermittent irrigation has significant environmental benefits. In particular, such a switch enables a drastic reduction in CH4 emissions, which were reduced by almost 100% in Tolima and Casanare. Notably, a 54% to 78% reduction in N2O emissions is observed in Tolima, 6% to 46% in rainfed systems, and 100% in irrigated systems when soil moisture was maintained near field capacity during fertilization in Casanare. Crop yield shows no significant differences in both regions. Intermittent irrigation reduced GWP by 62% to 85% in Tolima, and by 14% to 62% in rainfed systems, and 100% in irrigated systems in Casanare. This study concludes that shifting from flooded to intermittent irrigation minimizes rice production’s GWP and greenhouse gas emissions while preserving yields. Optimized water management contributes to reduced N2O emissions.

AbstractBackgroundThere is limited knowledge on how to increase soil organic carbon (SOC) stocks under tropical conditions. This study investigates SOC changes after converting land from native savanna (NS) to improved pasture (IP) land use.MethodsTwo acidic soil conversion sites were examined: (i) a poorly drained slope with medium‐texture soil (Casanare [CAS]1) and (ii) flat terrain with fine‐texture soil (CAS2). Another flat site was evaluated (Atlántico [ATL]), with fine‐textured to moderately textured neutral soil. Soil samples were collected and analyzed. SOC stocks (0–60 cm soil depth) were estimated, with a complex analysis of variance analyzing pasture type and soil depth.ResultsNS to IP conversion resulted in significant SOC accumulation in two regions, with losses in one (CAS2). ATL showed higher SOC accumulation than CAS. IP adoption led to SOC accumulation at depth (0–60 cm) after 10 years in CAS1. Elevated clay content in CAS2 favored SOC storage, while poorly drained areas hindered accumulation in CAS1. Cultivating rice before IP at CAS2 likely depleted SOC (0–20 cm), with 4 years of IP not restoring initial levels.ConclusionsAdopting IP over NS can increase SOC. Grassland type, soil properties, and land‐use change all influence SOC accumulation. These data inform sustainable land management for low‐emission livestock production.

CONTEXT OR PROBLEM:Most of the research evaluating rice varieties, a major global staple food, for greenhouse gas (GHG) mitigation has been conducted under continuous flooding. However, intermittent irrigation practices are expanding across the globe to address water shortages, which could alter emissions of methane (CH4) compared to nitrous oxide (N2O) for reducing overall global warming potential (GWP). To develop climate-smart rice production systems, it is critical to identify rice varieties that simultaneously reduce CH4 and N2O emissions while maintaining crop productivity under intermittent irrigation. OBJECTIVE:This study assessed CH4 and N2O emissions, grain yield, and GWP of four rice varieties cultivated under intermittent irrigation in Colombia. METHODS:Four common commercial rice varieties were evaluated over two seasons-wet and dry in 2020 and 2021-in two Colombian regions (Tolima and Casanare). RESULTS:Wet-season crop productivity was similar among varieties. However, F68 in Tolima and F-Itagua in Casanare significantly reduced yields in the dry season, likely due to periods of crop water stress. Overall, CH4 emissions and GWP were relatively low due to frequent field drainage events, with GWP ranging from 349 to 4704 kg CO2 equivalents ha-1. Accordingly, N2O emissions contributed 73% to GWP across locations, as wet-dry cycles can increase N2O emissions, creating a tradeoff for GWP when reducing CH4 through drainage. Varieties F67 in Tolima and F-Itagua in Casanare significantly reduced GWP by 32-61% across seasons, primarily by decreasing N2O rather than CH4 emissions. CONCLUSIONS:Rice varietal selection achieved significant GWP mitigation with limited impacts on grain yield, mainly due to reduced N2O emissions under non-continuously flooded irrigation. IMPLICATIONS/SIGNIFICANCE:This research underscores the critical role of rice varietal selection in addressing global climate-change and water-scarcity challenges, which drive the adoption of intermittent irrigation practices. By focusing on reducing N₂O emissions through appropriate variety selection, this study provides valuable insights for rice systems worldwide that are adapting to these pressing environmental challenges.

Rice demand in Latin America is increasing rapidly, but few studies have identified management practices to reduce water demand and soil greenhouse gas (GHG) emissions for irrigated rice systems in this region. Therefore, we tested the hypothesis that alternate wetting and drying (AWD) irrigation could maintain crop yields while mitigating global warming potential (GWP) compared to a conventional system with recommended irrigation and nutrient management practices for tropical rice in Colombia. Over four consecutive growing seasons, we monitored CH4 and N2O emissions, grain yield, and water consumption for two AWD treatments (AWD5 cm and AWD10 cm - where water drained to depths of 5 and 10 cm below the soil surface, respectively) and a control, in which the field was drained multiple times during fertilizer applications and then continuously flooded until harvest. The control had the highest water use across all rice seasons, with values ranging from 9260 to 16559 m3 ha-1 harvest-1. Implementation of AWD reduced cumulative water use by 19-56%, especially in dry seasons. Both AWD treatments significantly reduced cumulative CH4 emissions by 72-100%, which is consistent with previous research. A new finding is that AWD also decreased N2O emissions by 12-70%, which was attributed to management of soil moisture during fertilizer application events. In total, AWD reduced GWP by 25-73% compared to the control, with minimal impacts on crop productivity. Rice yields ranged from 5.2 to 8.2 Mg ha-1, with no significant difference among treatments in three of four seasons. This study shows that AWD saves irrigation water while greatly reducing GWP with little agronomic penalty, suggesting this technology could be a promising strategy for GHG mitigation in tropical rice in Colombia. Because there are important barriers to AWD adoption, future work should explore challenges at the farm-level as well as changes in policy, irrigation infrastructure, and institutional arrangements to understand the potential for broader implementation.

Sugarcane is an important crop for tropical countries and to accurately inventory its greenhouse gas (GHG) emissions baseline measurements are needed. In Colombia, sugarcane is one of the most important crops in terms of cultivated area and, paradoxically, scientific information reporting GHG emissions based on field measurements is almost nonexistent. The objective of this work was to quantify the direct emissions of carbon dioxide (CO 2 ) and nitrous oxide (N 2 O) in the sugarcane-soil system of the Cauca river valley, Colombia. For this purpose, a field experiment was established in a typic haplustert soil cropped with sugarcane. The effects of nitrogen (N) fertilization and sampling site on its GHG emissions were tested using the closed static chamber method over a period of 211 days. The main cumulative emissions were 765.14 ± 34.1 g CO 2 –C m −2 and 125.4 ± 22.6 mg N 2 O–N m −2 . Overall, GHG emissions were modified by N fertilization, the sampling site, and their interaction. Nitrogen fertilization with urea increased mean and cumulative CO 2 and N 2 O emissions, especially at the row sampling site. This paper highlights the importance of considering these factors when the quantification of GHGs or a reduction of their associated uncertainties are required. This work reportss the first GHG emissions data for a typical sugarcane agroecosystem in Colombia.

Maintenance therapy with Lenalidomide or proteasome inhibitors after autologous stem cell transplantation (ASCT) in multiple myeloma (MM) is an important component of first line treatment, resulting in deepening response (DR), converting PR to VGPR/CR or VGPR to CR in most patients and, in significantly longer PFS and OS. Of note, randomised clinical trials and real-world data confirm that DR also occurs in about 30% of patients receiving placebo or no maintenance at all. We analysed 90 patients with MM treated with first line ASCT in Hammersmith Hospital between 2017 - 2020, who did not receive maintenance therapy. We observed DR in 20 patients (22%) in the first two years. Patients achieving a DR had significantly higher PFS at 36 months post ASCT (89.4% v 41.1%, p=0.001 - Figure 1A). Baseline and ASCT characteristics, including high-risk cytogenetics, ISS, induction therapy and conditioning were comparable in DR and non-DR patients, however the use of the CXCR4 antagonist Plerixafor plus G-CSF vs G-CSF alone in the mobilisation regimen was associated with a higher probability for DR in the first 24 months post ASCT (58.3% v 23.2%, p=0.011 - Figure 1B). We suggest that improvement in depth of response after ASCT without pharmacological intervention indicates an immune anti-MM effect, underpinned by the immune composition of autologous grafts. We used 14-colour flow cytometry to analyse the immune cell frequencies in graft in 59 of the above patients, including 17 patients mobilised with Plerixafor plus G-CSF and 42 with G-CSF alone. The cell dose of each cell population was calculated from the relative frequency of CD34 cells in the graft and the CD34 cell dose infused in ASCT. In line with previous reports, the use of Plerixafor results in higher frequency and cell dose (in x10^6 cells/kg) of T cells in the graft (70.6% v 61.3%, p=0.015 and 306.2 v 161.4, p=0.007), driven mostly by a higher frequency (67.8% v 48.7%, p= 0.001) and dose (224 v 78.2, p=0.001) of central memory (CM) CD4 T cells. On the contrary, frequency and cell dose of effector memory (EM) CD4 T cells in Plerixafor plus G-CSF mobilised grafts were lower (6.7% v 21.5%, p=0.006 and 15.5 v 34.7, p=0.063). Apart from mobilisation regimen, univariate analysis showed a higher probability of achieving DR in grafts with high frequency of CD4 CM T cells (p= 0.012), NK cells (p=0.018 , Figure 1C), CD8 CM cells (p=0.06), higher dose of CD8 memory stem cells (p=0.033), lower frequency and dose of CD4 EM (p= 0.017 and p=0.007) and a lower dose of CD4 terminal effectors (TE) (p=0.039). In multivariate analysis, only a high NK cell frequency (p=0.011) and low CD4 TE cell dose (p=0.01), driven by their PD1 expression, predicted a higher probability for DR. Tregs frequency and cell dose were not affected from mobilisation regimen. However, Tregs dose was the stronger predictor of PFS at 36 months (75% with dose <5.06 x10^6/kg v 34.5% with dose >5.06 x10^6/kg, p= 0.001). Similarly, lower cell doses of CD4 EM (p=0.012) and frequency of CD4 TE (p=0.034) predicted a higher probability of PFS, but only Tregs cell dose retained significance in multivariate analysis (Figure 1D, p=0.001). In conclusion, spontaneous DR occurs in the first 2 years post ASCT in the absence of maintenance therapy and is associated with better PFS. CD4 memory subsets and NK cell graft composition appears significant for a potential immunological effect in DR. Additionally, a lower cell dose of immunosuppressive Tregs appears more important for sustaining long-term remission post ASCT.

SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have reduced hospitalisations and deaths, but vaccine efficacy in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. The MARCH database is a retrospective observational study of serological responses in patients with blood disorders. Here we present data on 381 patients with haematological malignancies. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued suboptimal vaccine responses who may benefit from additional doses, prophylactic extended half-life neutralising monoclonal therapies (nMAB) or prompt nMAB treatment in the event of SARS-CoV-2 infection.

Abstract SARS-CoV-2 infection, and resulting disease, COVID-19, has a high mortality amongst patients with haematological malignancies. Global vaccine rollouts have successfully reduced hospitalisations and deaths, but the efficacy of vaccination in patients with haematological malignancies is known to be reduced. The UK-strategy offered a third, mRNA-based, vaccine as an extension to the primary course in these patients. Here we quantify serological responses following these vaccines in a cohort of 381 patients with haematological malignancies attending routine haematology outpatient clinics. By comparison with healthy controls, we report suboptimal responses following two primary vaccines, with significantly enhanced responses following the third primary dose. These responses however are heterogeneous and determined by haematological malignancy sub-type and therapy. We identify a group of patients with continued sub-optimal vaccine responses who may benefit from additional doses, as well as early intervention with monoclonal therapies in the event of developing SARS-CoV-2 infection.

Grazing-based production systems are a source of soil greenhouse gas (GHG) emissions triggered by excreta depositions. The adoption of Urochloa forages (formerly known as Brachiaria) with biological nitrification inhibition (BNI) capacity is a promising alternative to reduce nitrous oxide (N2O) emissions from excreta patches. However, how this forage affects methane (CH4) or carbon dioxide (CO2) emissions from excreta patches remains unclear. This study investigated the potential effect of soils under two Urochloa forages with contrasting BNI capacity on GHG emissions from cattle dung deposits. Additionally, the N2O and CH4 emission factors (EF) for cattle dung under tropical conditions were determined. Dung from cattle grazing star grass (without BNI) was deposited on both forage plots: Urochloa hybrid cv. Mulato and Urochloa humidicola cv. Tully, with a respectively low and high BNI capacity. Two trials were conducted for GHG monitoring using the static chamber technique. Soil and dung properties and GHG emissions were monitored in trial 1. In trial 2, water was added to simulate rainfall and evaluate GHG emissions under wetter conditions. Our results showed that beneath dung patches, the forage genotype influenced daily CO2 and cumulative CH4 emissions during the driest conditions. However, no significant effect of the forage genotype was found on mitigating N2O emissions from dung. We attribute the absence of a significant BNI effect on N2O emissions to the limited incorporation of dung-N into the soil and rhizosphere where the BNI effect occurs. The average N2O EFs was 0.14%, close to the IPCC 2019 uncertainty range (0.01-0.13% at 95% confidence level). Moreover, CH4 EFs per unit of volatile solid (VS) averaged 0.31 g CH4 kgVS-1, slightly lower than the 0.6 g CH4 kgVS-1 developed by the IPCC. This implies the need to invest in studies to develop more region-specific Tier 2 EFs, including farm-level studies with animals consuming Urochloa forages to consider the complete implications of forage selection on animal excreta based GHG emissions.

Background: It would be clinically useful to prospectively identify the risk of disease progression in chronic myeloid leukaemia (CML). Overexpression of cancerous inhibitor of protein phosphatase 2A (PP2A) (CIP2A) protein is an adverse prognostic indicator in many cancers. Methods: We examined CIP2A protein levels in diagnostic samples from the SPIRIT2 trial in 172 unselected patients, of whom 90 received imatinib and 82 dasatinib as first-line treatment. Results: High CIP2A levels correlated with inferior progression-free survival (p = 0.04) and with worse freedom from progression (p = 0.03), and these effects were confined to dasatinib recipients. High CIP2A levels were associated with a six-fold higher five-year treatment failure rate than low CIP2A levels (41% vs. 7.5%; p = 0.0002), in both imatinib (45% vs. 11%; p = 0.02) and dasatinib recipients (36% vs. 4%; p = 0.007). Imatinib recipients with low CIP2A levels had a greater risk of treatment failure (p = 0.0008). CIP2A levels were independent of Sokal, Hasford, EUTOS (EUropean Treatment and Outcome Study), or EUTOS long-term survival scores (ELTS) or the presence of major route cytogenetic abnormalities. No association was seen between CIP2A levels and time to molecular response or the levels of the CIP2A-related proteins PP2A, SET, SET binding protein 1 (SETBP1), or AKT. Conclusions: These data confirm that high diagnostic CIP2A levels correlate with subsequent disease progression and treatment failure. CIP2A is a simple diagnostic biomarker that may be useful in planning treatment strategies.

Cassava production requires nitrogen (N) inputs to drive processes such as protein synthesis. Nevertheless, N not taken up by cassava roots is subjected to microbial transformation resulting in nitrous oxide (N 2 O) production, a potent greenhouse gas. The temporal dynamics of soil N is partially influenced by the N source (i.e., organic or inorganic fertilizer) and the synchrony between N supply and demand. This study, which was conducted in Colombia on soils with high organic carbon and phosphorus contents, aimed at monitoring N 2 O emissions from cassava plots fertilized with organic (49.8 kg N ha ‐1 year ‐1 ) or inorganic fertilizers (22.7 kg N ha ‐1 year ‐1 ). Although the organic fertilizer (vermicompost) contained more than double the amount of N, cumulative N 2 O emissions from organic cassava production (1.28 kg N 2 O‐N ha ‐1 ) were lower than those from inorganic fertilizer‐based cassava production (1.74 kg N 2 O‐N ha ‐1 ) system. This finding indicates that, if crop yields can be maintained, there is potential to reduce cassava production's environmental impact through organic fertilization on highly fertile soils. However, a transition to organic fertilization depends on the availability of sufficient amounts of organic fertilizers at the farm level. The N 2 O emissions in this study were higher than those predicted using the default IPCC emission factor, which confirmed the relevance of using country or regional specific emissions factors.

Acute myeloid leukaemia (AML) relapse rates are high, at 60–80% within three years of diagnosis.1 This may be due to sequestration of chemoresistant leukaemic stem cells within the bone marrow (BM) microenvironment.2 Mesenchymal stromal cells (MSCs) are the common progenitor for BM stroma, and can differentiate into cells of mesodermal origin.3 Previous reports have shown that mesenchymal stromal cell (MSC) modification without functional alteration of the haematopoietic system causes subsequent myelodysplasia and secondary leukaemia in murine models.4 In this study, we characterise the impact of primary patient-derived AML cells upon MSC populations in an ex vivo setting. Our findings identify key differentially expressed genes across the MSC transcriptome in the context of AML, and compare the difference in gene expression between normal and cancer phenotypes. We identify both well-established and novel genes. The latter may confer growth benefits by upregulating canonical cancer pathways in AML cells, such as Wnt/β-catenin (as in the case of secreted frizzled related protein 4, SFRP4), or altering immune and metabolic pathways (such as retinoic acid receptor responder 1, RARRES1). These may constitute novel targets for therapeutic interventions targeting the BM microenvironment. MSC samples from a normal paediatric donor, provided by the John Goldman Centre for Cellular Therapy (Hammersmith Hospital, London) were immunophenotyped by staining with the standard reference panel of labelled mouse anti-human antibodies (CD105-APC, CD73-PE, CD90-APC, CD45-FITC, CD34-PE, CD3-APC, CD19-PE, HLA-DR-FITC and CD14-PE; BD Biosciences, Franklin Lakes, NJ, USA) as defined by the International Society of Cellular Therapy5 using a FACS Canto II analyser (BD Biosciences) on FACS Diva software. These were plated into the lower compartments of a 24-well plate with 0·4 µm polycarbonate Transwell inserts (Corning, Corning, NY, USA) and incubated for 24 h. At 24 h, AML blasts or normal cells were plated into the upper compartment of each well. In total, triplicate co-cultures were set up for three individual AML blast donors (characteristics shown in Table I) and one normal CD34+ donor, with the remaining 12 wells used as a negative control (upper compartment empty). After 72 h of co-culture, RNA was extracted from MSCs using the RNeasy Mini kit (QIAGEN, Hilden, Germany) per the manufacturer's instructions and paired-end sequencing undertaken on the HiSeq 4000 system (Illumina, San Diego, CA, USA). Differential gene expression analysis was then performed (see Figure S1 for details). 46,XX,?t(16;16)(p13;q22) [4]/46,XX[14] Overall, analysis yielded 57 differentially expressed genes in MSCs when comparing the transcript numbers in AML MSCs against non patient (NP) MSCs: 26 protein-coding genes, 8 processed pseudogenes, 12 micro-RNAs, 4 small nucleolar RNAs, 4 long non-coding RNAs and 3 miscellaneous RNAs (Table II). Forty-seven of these were upregulated in AML MSCs, and 10 were downregulated. Differentially expressed protein-coding genes could broadly be categorised according to their function in the context of cancer, with many being previously identified in either AML or in solid tumours (Table IIa). In total, 20 were reported to be pro-growth or anti-apoptosis; 19 were involved in extracellular matrix breakdown or tumour invasion; 2 conferred chemoresistance; 19 had inflammatory and immunomodulatory functions; and 4 altered cellular metabolism. Some genes fell into multiple categories. Furthermore, 15 of the proteins coded by these genes are secreted by cells, and 3 are membrane proteins. Over half of the identified differentially expressed genes were non-coding elements. These have been reported as having complex expression profiles and putative effects in the context of cancer.6 We identified several MSC genes that are well established in the literature as beneficial to AML, such as the CXCL family, suggesting our study methods were valid. For example, CXCL8, a pro-inflammatory cytokine with neutrophil attractant properties which activates several canonical cancer pathways including MAPK and PI3K,7 was upregulated in our study [4·25 log2-fold change; (LFC)]. Two genes of potential interest identified in this study were SFRP4 and RARRES1, both of which were downregulated in AML MSCs (−1·15 and −1·54 LFC respectively). SFRP4 is a secreted protein which acts by inhibiting the Wnt/β-catenin pathway.8 Enhanced activity of Wnt/β-catenin has been shown in both AML cell lines and primary blasts,9 and SFRP4 downregulation predicts poor prognosis in AML subtypes.10 One of the mechanisms for this may be through decreased SFRP4 secretion by MSCs. MAPK/mTOR pathway activity is enhanced in AML.11 This study found downregulation of RARRES1, a known MAPK/mTOR pathway repressor and autophagy inducer.12 RARRES1 has also been associated with metabolic shifts towards de novo lipogenesis in AML13 and in vivo alterations of haematopoietic progenitor cell (HPC) proliferation and differentiation.14 Since RARRES1 is not a secreted protein, it is unlikely to directly reduce mTOR pathway activity in AML cells; however, these pleiotropic effects may be a result of alterations in other secreted proteins. This warrants further investigation. MSCs for experiments were sourced from a paediatric donor, as paediatric cells may have greater growth potential and resilience than those from older donors. However, there remains a concern that the expression profiles obtained may differ based on donor age. Although this exploratory study used primary patient-derived cells to maximise similarity to clinical phenotypes, small sample sizes limited the available analyses. This was partially mitigated using NOISeq, an R package for differential gene expression analysis which has been demonstrated to have a lower false discovery rate at sample sizes of three or fewer than other alternatives.15 Unfortunately, due to the Covid-19 pandemic, we were unable to mechanistically validate identified genes. In conclusion, this study utilised a well-established co-culture model to investigate transcriptome-wide gene expression alterations in BM MSCs in the context of AML using primary patient-derived cells. Several differentially expressed genes had pleiotropic effects, conferring benefits upon AML cells through diverse mechanisms. Although mechanistic studies will be required to validate and expand upon these findings, this study provides an initial basis from which to further characterise AML–BM interactions. In particular, we identify SFRP4 and RARRES1 as potential novel routes through which MSC modification may augment AML cell survival. This work was supported by grants from Leuka and The Friends of Hammersmith Hospital. The Imperial BRC Genomics Facility has provided resources and support that have contributed to the research results reported within this study. The authors are grateful to Anna M Eiring, PhD, from Texas Tech University Health Science Center El Paso, for her comments and advice on the manuscript. AC performed the experiments, analysed the data and wrote the manuscript; SL and EYF provided research material and reviewed the manuscript; ENM and JFA advised on the clinical aspect of the project and reviewed the manuscript; JSK designed the experiments, supervised the project and reviewed the manuscript. The authors have no conflicts of interest to declare. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Con el propósito de evaluar las emisiones de metano y óxido nitroso en el suelo a través del método de cámaras estáticas cerradas en tres sistemas de uso; bosque secundario, sistema agroforestales Quesungual y sistema tradicional agrícola, en la micro cuenca Tecomapa, Somotillo, Nicaragua, setenta y dos cámaras estáticas cerradas fueron establecidas en seis fincas localizadas en la unidad hidrográfica Tecomapa, Nicaragua en 2014, para evaluar las emisiones de Metano (CH4) y Óxido Nitroso (N2O), en los sistemas de uso de suelo: Bosque secundario, Quesungual y Sistema Tradicional agrícola. Como resultado, mayores emisiones de N2O y CH4, se observaron en el mes más lluvioso (septiembre 2014). El sistema Quesungual fue sumideros de CH4 a nivel de flujos netos acumulados (p>F=0.0133), y el sistema tradicional el mayor emisor de este gas. La mayor emisión de N2O tiende a ocurrir en el sistema tradicional. Finalmente el gas metano se asoció positivamente al N2O (r2= 1; p>F= 0.0533), y el WFPS tiende a asociarse negativamente a la temperatura y gases CH4 y N2O.

Tyrosine kinase inhibitors (TKIs), the treatment of choice for chronic myeloid leukaemia (CML), can cause lower gastrointestinal (GI) toxicity which is manifested as diarrhoea. The mechanisms are not fully understood. The enteroendocrine signalling compound, serotonin (5-HT), is important for regulating peristaltic motion, fluid secretion and visceral hypersensitivity in the GI tract, and has been implicated in diseases such as irritable bowel syndrome. In this study, we have evaluated whether TKI-induced diarrhoea may be related to variation in the serotonin re-uptake transporter (SERT) gene. CML patients with and without diarrhoea on the SPIRIT2 trial (imatinib, n = 319; and dasatinib, n = 297) were genotyped for the promoter 5-HTTLPR, intron 2 VNTR and rs25531 polymorphisms by PCR-based methods. Diarrhoea was more prevalent in imatinib, than in dasatinib treated patients (P = 0.015), which when stratified by gender was seen to be driven by female patients (P = 0.036). Logistic regression analysis revealed that age, and the dominant HTTLPR with the rs25531 single nucleotide polymorphism (SNP) model, explained the occurrence of diarrhoea in ~10% of imatinib-treated female CML patients. These data suggest SERT polymorphisms influence imatinib-induced diarrhoea but not that of dasatinib.