Antarctic ice sheet fertilises the Southern Ocean

Open access journalSouthern Ocean (SO) marine primary productivity (PP) is strongly influenced by the availability of iron in surface waters, which is thought to exert a significant control upon atmospheric CO2 concentrations on glacial/interglacial timescales. The zone bordering the Antarctic Ice Sheet exhibits high PP and seasonal plankton blooms in response to light and variations in iron availability. The sources of iron stimulating elevated SO PP are in debate. Established contributors include dust, coastal sediments/upwelling, icebergs and sea ice. Subglacial meltwater exported at the ice margin is a more recent suggestion, arising from intense iron cycling beneath the ice sheet. Icebergs and subglacial meltwater may supply a large amount of bioavailable iron to the SO, estimated in this study at 0.07-0.2 Tg yr-1. Here we apply the MIT global ocean model (Follows et al., 2007) to determine the potential impact of this level of iron export from the ice sheet upon SO PP. The export of iron from the ice sheet raises modelled SO PP by up to 40%, and provides one plausible explanation for seasonally very high in situ measurements of PP in the near-coastal zone. The impact on SO PP is greatest in coastal regions, which are also areas of high measured marine PP. These results suggest that the export of Antarctic runoff and icebergs may have an important impact on SO PP and should be included in future biogeochemical modelling.Philip Leverhulme PrizeLeverhulme Research FellowshipLeverhulme TrustRoyal Society Fellowship7th European Community Framework Programme - Marie Curie Intra European FellowshipNatural Environment Research Council (NERC

Estudio de factibilidad para la implementación de una planta procesadora de citricos en fresco en el distrito de San Ramón, Departamento de Junín

Hoy en día la agricultura se encuentra en una etapa de desarrollo, el crecimiento se viene dando con la siembra de nuevas áreas de cultivo. En Junín se encuentra la mayor producción de cítricos en sus variedades de naranja, tangelo y limón dulce, hay una demanda insatisfecha por el servicio de procesado de cítricos en frescos. También un punto relevante es que las actuales procesadoras de cítricos que brindan el servicio de acondicionamiento de los cítricos no se han adecuado a las exigencias del mercado de abastos ( Mercado de frutas # 2 ). En la presente investigación se analiza el mercado llegando a la conclusión que el mercado objetivo son los agricultores de la zona que procesan sus cítricos para su envío al mercado de abastos. El presente informe de investigación se estructuro en diez capítulos que cubren aspectos generales relacionados con el tema para la implementación de una planta procesadora de cítricos en fresco en el Distrito de San Ramón Departamento Junín. Se utilizo estudios de mercados para saber la demanda proyectada a 5 años, mercados objetivos, estudio de las competencias directas e indirectas. Se determinó el tamaño y ubicación de la planta utilizando la matriz de localización y factores tanto económicos como estratégicos. Se tuvo en cuanta el estudio del impacto ambiental ya que nuestros residuos son sólidos. En cuanto a la parte financiera y económica de demostrar la factibilidad del proyecto tanto técnico como económico mediante indicadores económicos, estado de perdidas y ganancias, análisis de sensibilidad; además, presenta otras secciones tales como las conclusiones, recomendaciones, anexos, bibliografía entre otros, que complementan y expresan en forma sintética los resultados y otros aspectos relevantes de la presente investigación que dejamos a su consideración. Today, agriculture is at a stage of development, growth has been going on with the planting of new areas of cultivation. In Junín is the largest citrus fruit in the varieties of orange, lemon and sweet tangelo is an unmet demand and the demand is greater than supply of processing citrus service in fresh. Also a relevant point is that the current citrus processors offer the service of packaging of citrus have not been adequate to the demands of the wholesale market (Market of fruits # 2). The present research analyzes the market and concluded that the target market are farmers in the area to process their citrus for shipment to the Market. This research report is divided into ten chapters covering general aspects related to the theme for the implementation of a citrus processing plant fresh in the District of San Ramon Junin Department. Market research was used to determine the projected demand for five years, market objectives, study of direct and indirect competition. We determined the size and location of the plant using the array of location and both economic and strategic factors. It took into account the environmental impact study of our waste is solid. As for the financial and economic fulfilled the main objective of the project was to demonstrate the technical feasibility – economic indicators of the project throught economic, profit and loss statement, sensitivity analysis, also has other sections such as the conclusions, recomendations, appendices, bibliography and others that complement and expressed as a summary of the results and other relevant aspects of this research to let her entertained.Tesi

The GATA1s isoform is normally down-regulated during terminal haematopoietic differentiation and over-expression leads to failure to repress MYB, CCND2 and SKI during erythroid differentiation of K562 cells

Background: Although GATA1 is one of the most extensively studied haematopoietic transcription factors little is currently known about the physiological functions of its naturally occurring isoforms GATA1s and GATA1FL in humans—particularly whether the isoforms have distinct roles in different lineages and whether they have non-redundant roles in haematopoietic differentiation. As well as being of general interest to understanding of haematopoiesis, GATA1 isoform biology is important for children with Down syndrome associated acute megakaryoblastic leukaemia (DS-AMKL) where GATA1FL mutations are an essential driver for disease pathogenesis. <p/>Methods: Human primary cells and cell lines were analyzed using GATA1 isoform specific PCR. K562 cells expressing GATA1s or GATA1FL transgenes were used to model the effects of the two isoforms on in vitro haematopoietic differentiation. <p/>Results: We found no evidence for lineage specific use of GATA1 isoforms; however GATA1s transcripts, but not GATA1FL transcripts, are down-regulated during in vitro induction of terminal megakaryocytic and erythroid differentiation in the cell line K562. In addition, transgenic K562-GATA1s and K562-GATA1FL cells have distinct gene expression profiles both in steady state and during terminal erythroid differentiation, with GATA1s expression characterised by lack of repression of MYB, CCND2 and SKI. <p/>Conclusions: These findings support the theory that the GATA1s isoform plays a role in the maintenance of proliferative multipotent megakaryocyte-erythroid precursor cells and must be down-regulated prior to terminal differentiation. In addition our data suggest that SKI may be a potential therapeutic target for the treatment of children with DS-AMKL

Ocean forced variability of Totten Glacier mass loss

This is the author accepted manuscript. The final version is available from the Geological Society of London via the DOI in this record.A large volume of the East Antarctic Ice Sheet drains through the Totten Glacier (TG) and is thought to be a potential source of substantial global sea level rise over the coming centuries. We show the surface velocity and heightof the floating part of TG, which buttresses the grounded component, have varied substantially over two decades (1989–2011), with variations in surface height strongly anti-correlated with simulated basal melt rates (r=0.70, p<0.05). Coupled glacier/ice-shelf simulations confirm ice flow and thickness respond to both basal melting of the ice shelf and grounding on bed obstacles. We conclude the observed variability of TG is primarily ocean-driven. Ocean warming in this region will lead to enhanced ice-sheet dynamism and loss of upstream grounded ice.This work was supported by, Australian Antarctic Division projects 3103, 4077, 4287 and 4346, National Computing Infrastructure grant m68, NSF grant ANT-0733025, NASA grant NNX09AR52G (Operation Ice Bridge), NERC grant NE/F016646/1, NERC fellowship NE/G012733/2, the Jackson School of Geoscience, the Jet Propulsion Laboratory and the G. Unger Vetlesen Foundation. This research was also supported by the Australian Government’s Cooperative Research Centres Programme through the Antarctic Climate & Ecosystems Cooperative Research Centre. The work is also supported under the Australian Research Councils Special Research Initiative for Antarctic Gateway Partnership SR140300001. Landsat 4 and 7 images courtesy of the U.S. Geological Survey. This is UTIG contribution 2486. Thanks to Benoit Legresy for useful discussions

Response to Biologic Drugs in Patients with Rheumatoid Arthritis and Antidrug Antibodies

Importance: There are conflicting data on the association of antidrug antibodies with response to biologic disease-modifying antirheumatic drugs (bDMARDs) in rheumatoid arthritis (RA). Objective: To analyze the association of antidrug antibodies with response to treatment for RA. Design, Setting, and Participants: This cohort study analyzed data from the ABI-RA (Anti-Biopharmaceutical Immunization: Prediction and Analysis of Clinical Relevance to Minimize the Risk of Immunization in Rheumatoid Arthritis Patients) multicentric, open, prospective study of patients with RA from 27 recruiting centers in 4 European countries (France, Italy, the Netherlands, and the UK). Eligible patients were 18 years or older, had RA diagnosis, and were initiating a new bDMARD. Recruitment spanned from March 3, 2014, to June 21, 2016. The study was completed in June 2018, and data were analyzed in June 2022. Exposures: Patients were treated with a new bDMARD: adalimumab, infliximab (grouped as anti-tumor necrosis factor [TNF] monoclonal antibodies [mAbs]), etanercept, tocilizumab, and rituximab according to the choice of the treating physician. Main Outcomes and Measures: The primary outcome was the association of antidrug antibody positivity with EULAR (European Alliance of Associations for Rheumatology; formerly, European League Against Rheumatism) response to treatment at month 12 assessed through univariate logistic regression. The secondary end points were the EULAR response at month 6 and at visits from month 6 to months 15 to 18 using generalized estimating equation models. Detection of antidrug antibody serum levels was performed at months 1, 3, 6, 12, and 15 to 18 using electrochemiluminescence (Meso Scale Discovery) and drug concentration for anti-TNF mAbs, and etanercept in the serum was measured using enzyme-linked immunosorbent assay. Results: Of the 254 patients recruited, 230 (mean [SD] age, 54.3 [13.7] years; 177 females [77.0%]) were analyzed. At month 12, antidrug antibody positivity was 38.2% in patients who were treated with anti-TNF mAbs, 6.1% with etanercept, 50.0% with rituximab, and 20.0% with tocilizumab. There was an inverse association between antidrug antibody positivity (odds ratio [OR], 0.19; 95% CI, 0.09-0.38; P <.001) directed against all biologic drugs and EULAR response at month 12. Analyzing all the visits starting at month 6 using generalized estimating equation models confirmed the inverse association between antidrug antibody positivity and EULAR response (OR, 0.35; 95% CI, 0.18-0.65; P <.001). A similar association was found for tocilizumab alone (OR, 0.18; 95% CI, 0.04-0.83; P =.03). In the multivariable analysis, antidrug antibodies, body mass index, and rheumatoid factor were independently inversely associated with response to treatment. There was a significantly higher drug concentration of anti-TNF mAbs in patients with antidrug antibody-negative vs antidrug antibody-positive status (mean difference, -9.6 [95% CI, -12.4 to -6.9] mg/L; P < 001). Drug concentrations of etanercept (mean difference, 0.70 [95% CI, 0.2-1.2] mg/L; P =.005) and adalimumab (mean difference, 1.8 [95% CI, 0.4-3.2] mg/L; P =.01) were lower in nonresponders vs responders. Methotrexate comedication at baseline was inversely associated with antidrug antibodies (OR, 0.50; 95% CI, 0.25-1.00; P =.05). Conclusions and Relevance: Results of this prospective cohort study suggest an association between antidrug antibodies and nonresponse to bDMARDs in patients with RA. Monitoring antidrug antibodies could be considered in the treatment of these patients, particularly nonresponders to biologic RA drugs

Century-scale simulations of the response of the West Antarctic Ice Sheet to a warming climate

We use the BISICLES adaptive mesh ice sheet model to carry out one, two, and three century simulations of the fast-flowing ice streams of the West Antarctic Ice Sheet, deploying sub-kilometer resolution around the grounding line since coarser resolution results in substantial underestimation of the response. Each of the simulations begins with a geometry and velocity close to present-day observations, and evolves according to variation in meteoric ice accumulation rates and oceanic ice shelf melt rates. Future changes in accumulation and melt rates range from no change, through anomalies computed by atmosphere and ocean models driven by the E1 and A1B emissions scenarios, to spatially uniform melt rate anomalies that remove most of the ice shelves over a few centuries. We find that variation in the resulting ice dynamics is dominated by the choice of initial conditions and ice shelf melt rate and mesh resolution, although ice accumulation affects the net change in volume above flotation to a similar degree. Given sufficient melt rates, we compute grounding line retreat over hundreds of kilometers in every major ice stream, but the ocean models do not predict such melt rates outside of the Amundsen Sea Embayment until after 2100. Within the Amundsen Sea Embayment the largest single source of variability is the onset of sustained retreat in Thwaites Glacier, which can triple the rate of eustatic sea level rise

CCR7+ dendritic cells sorted by binding of CCL19 show enhanced Ag-presenting capacity and antitumor potency

Dendritic cell therapy has been a promising addition to the current armory of therapeutic options in cancer for more than 20 years but has not yet achieved breakthrough success. To successfully initiate immunity, dendritic cells have to enter the lymph nodes. However, experience to date of therapeutic dendritic cell administration indicates that this is frequently an extremely inefficient process. The major regulator of dendritic cell migration to the lymph nodes is the chemokine receptor CCR7 and in vitro generated dendritic cells typically display heterogeneous expression of this receptor. Here we demonstrate that positive selection for the dendritic cell subpopulation expressing CCR7, using a chemically-synthesized ligand:CCL19, enriches for cells with enhanced lymph node migration and Ag presentation competence as well as a chemokine expression profile indicative of improved interactions with T cells. This enhanced lymph node homing capacity of enriched CCR7+ cells is seen in comparison to a population of unsorted dendritic cells containing an equivalent number of CCR7+ dendritic cells. Importantly, this indicates that separating the CCR7+ dendritic cells from the CCR7− cells, rather than simple CCL19 exposure, is required to affect the enhanced lymph node migration of the CCR7+ cells. In models of both subcutaneous and metastatic melanoma, we demonstrate that the dendritic cells sorted for CCR7 expression trigger enhanced CD8 T-cell driven antitumor immune responses which correlate with reduced tumor burden and increased survival. Finally, we demonstrate that this approach is directly translatable to human dendritic cell therapy using the same reagents coupled with clinical-grade flow-cytometric sorting

The implications of defining obesity as a disease: a report from the Association for the Study of Obesity 2021 annual conference

Unlike various countries and organisations, including the World Health Organisation and the European Parliament, the United Kingdom does not formally recognise obesity as a disease. This report presents the discussion on the potential impact of defining obesity as a disease on the patient, the healthcare system, the economy, and the wider society. A group of speakers from a wide range of disciplines came together to debate the topic bringing their knowledge and expertise from backgrounds in medicine, psychology, economics, and politics as well as the experience of people living with obesity. The aim of their debate was not to decide whether obesity should be classified as a disease but rather to explore what the implications of doing so would be, what the gaps in the available data are, as well as to provide up-to-date information on the topic from experts in the field. There were four topics where speakers presented their viewpoints, each one including a question-and-answer section for debate. The first one focused on the impact that the recognition of obesity could have on people living with obesity regarding the change in their behaviour, either positive and empowering or more stigmatising. During the second one, the impact of defining obesity as a disease on the National Health Service and the wider economy was discussed. The primary outcome was the need for more robust data as the one available does not represent the actual cost of obesity. The third topic was related to the policy implications regarding treatment provision, focusing on the public's power to influence policy. Finally, the last issue discussed, included the implications of public health actions, highlighting the importance of the government's actions and private stakeholders. The speakers agreed that no matter where they stand on this debate, the goal is common: to provide a healthcare system that supports and protects the patients, strategies that protect the economy and broader society, and policies that reduce stigma and promote health equity. Many questions are left to be answered regarding how these goals can be achieved. However, this discussion has set a good foundation providing evidence that can be used by the public, clinicians, and policymakers to make that happen

Initiation of the West Antarctic Ice Sheet and estimates of total Antarctic ice volume in the earliest Oligocene

Reconstructions of Antarctic paleotopography for the late Eocene suggest that glacial erosion and thermal subsidence have lowered West Antarctic elevations considerably since then, with Antarctic land area having decreased ~20%. A new climate-ice sheet model based on these reconstructions shows that the West Antarctic Ice Sheet first formed at the Eocene-Oligocene transition (33.8–33.5 Ma, E-O) in concert with the continental-scale expansion of the East Antarctica Ice Sheet and that the total volume of East and West Antarctic ice (33.4–35.9 × 106 km3) was >1.4 times greater than previously assumed. This larger modeled ice volume is consistent with a modest cooling of 1–2°C in the deep ocean during the E-O transition, lower than other estimates of ~3°C cooling, and suggests the possibility of substantial ice in the Antarctic interior before the Eocene-Oligocene boundary