devinitorg/iati-policy-markers huggingface dataset:
iPSC-derived cardiomyocytes to model estrogen receptor modulation of stress cardiomyopathy and arrhythmic syndromes It has long been known that young women are relatively protected from heart disease compared to men. For sudden death arising from disrupted heart rhythm, men are 80% more likely to be affected. This often occurs after sudden or chronic stress, and is triggered by adrenaline. We have been studying a newly described syndrome in which a sudden extreme shock (accident, bereavement) produces not sudden death, but a temporary reduction in heart function which then reverses.  Sufferers come in to hospital thinking they are having a heart attack, but recover within days to weeks to have normal heart function. Interestingly, 80-90% of sufferers are women around or after the menopause.  We reproduced this in an anesthetised rat model, and showed that a single dose of adrenaline could give the same effect.  (In fact one dose of adrenaline from an epi-pen can sometimes have the same result in people). We found that very high adrenaline could switch from being stimulant to depressant, through an effect on its receptors on the heart cell surface.  When we tried to stop it being depressant on the heart function, we induced sudden cardiac death. Our idea is that high adrenaline goes from being stimulant (but damaging) to depressant (but protective) through a receptor switch, and that this protects against sudden death.  Here we want to know why this happens particularly in women at a time when estrogen is dropping, and whether this can give us insights into male/female differences.  For these experiments we want to move away from animal models to human pluripotent stem cells (hPSC).  We know hPSC can reliably be turned into beating cardiac cells (hPSC-CM), and that they can show the same disrupted rhythm as a patient from which they came. They have adrenaline receptors more like human than are found in animal species, and adrenaline can produce the same kind of rhythm effects in the dish as in the whole heart.  They are also very long-lasting in culture, and can be more easily experimented on - for example to turn off and on specific proteins.  We already have ways to measure their beating activity and how easily they can be damaged.  We also have a number of hPSC lines reflecting different natural gene variation in human populations. We aim to discover the mechanism of the adrenaline switch and how it can be changed by female hormones.  The ideal goal for us would be to find a way to harness the protective effect without producing the temporary loss of heart function, and to develop a drug to use that mechanism.  One other advantage of the hPSC-CM is that they can be produced in large quantities and used in multiple assays at the same time.  The same cells and methods are being used now by pharmaceutical companies to test drugs, which means that any of our promising findings can go more quickly into drug development. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Steroid Receptors as targets for myelin regeneration by endogenous adult neural stem cells The nerve fibres of the brain and spinal cord (the CNS) are surround by an insulating material called myelin that protects the fibres and allows them to carry electrical impulses very rapidly. Myelin is made by a cell called an oligodendrocyte. This cell is the primary target in several neurological diseases most notably multiple sclerosis (MS). Early in the disease the brains own stem cells are able to replace the lost oligodendrocytes and hence myelin can be restored (a regenerative process called remyelination). However, as the disease progresses and the patient ages remyelination becomes less efficient and the fibres are left without their myelin: in this state they are very vulnerable to irreversible degeneration. Therapies that enhance remyelination will have a major impact on the treatment of MS - however, none currently exist. In this project UK and Chinese laboratories will strengthen an existing collaboration to test the ability of a naturally-derived plant compound called diosgenin, which is already in clinical use, to enhance remyelination in laboratory models of MS and will continue studies to understand the mechanisms of action of diosgenin in remyelination. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
UK-Brazil Joint Centre for Arbovirus Discovery, Diagnosis, Genomics and Epidemiology (CADDE) Recently, Brazil has been affected by unexpected and explosive epidemics of insect-transmitted viruses (arboviruses), most notably Zika, chikungunya, dengue, and yellow fever viruses. The huge economic burden of the Zika epidemic in Brazil and the widespread presence of urban mosquitos in the country highlight an urgent need for accurate predictions of disease spread, particularly in large, densely populated regions. Our UK-Brazil Partnership (CADDE) will enhance and expand an excellent existing collaborations, with the aim of anticipating and controlling future epidemics of arboviruses in Brazil. It is our vision for CADDE to become a strategic centre of excellence for research in South America that focuses on providing timely analysis, based on genomic, epidemiological and geographic evidence, to anticipate and control transmission of arboviruses, today and in the future..   Our research questions include: 1) What arboviruses circulate in human, mosquito and reservoir populations in Brazil? 2) Where and how do arboviruses persist during non-epidemic periods? 3) What are the biological and medical implications of the genetic diversity of circulating arboviruses and of mutations in their genomes? 4) What factors control the transformation of a single introduction of a new arbovirus into human populations into sizeable epidemic, and 5) how quickly can we detect and characterise such epidemics, and how best to respond? Active virus surveillance in vectors and reservoirs will be combined with seroprevalence surveys in blood donors (to characterise features such as virus genomics, transmission, and immunity). Novel portable genome sequencing technologies and modern real-time epidemiological analyses will be applied to the most important arboviruses in Brazil.   Using modern techniques that can unify the information from genomics and epidemiology, CADDE will strengthen the evidence base for public health actions, and strengthen the capacity of Brazilian health system to respond to emerging arboviral diseases. We will transform local capacity by training research scientists and public health personnel in field epidemiology, laboratory testing, the use of portable genomic technologies, and computational and statistical methods. COVID-19 The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001 The effects of tetrathiomolybdate, a donator of hydrogen sulphide, in animal models of brain ischemia Ischaemia (low oxygen) occurs when blood flow to a vital organ (e.g., heart, brain) is insufficient to meet metabolic demand. This leads to death of tissue and loss of function (i.e., as in heart attack, stroke). Presently, there are limited strategies to deal with ischaemia. Although reopening blood vessels (reperfusion) is a necessary, often lifesaving treatment that improves long-term outcome, 'reperfusion injury' upon restoration of blood supply can cause further damage. Attempts to decrease reperfusion injury have recently focussed on decreasing metabolism. For example, after cardiac arrest and resuscitation, decreasing body temperature (therapeutic hypothermia) may have a protective effect, although this takes time to initiate. Giving a drug that can decrease metabolism more rapidly could provide added benefit in this scenario. Hydrogen sulphide given either in gas form or intravenously could induce a state of 'suspended animation' in mice with marked reductions in core temperature and metabolic rate (Blackstone, Science 2005). However, this was far less effective in modulating metabolism in larger species, including rats. We made the novel discovery that the copper-modulating drug, tetrathiomolybdate (TTM), was a slow-releaser or hydrogen sulphide, and could safely induce suspended animation in rats, whereas native hydrogen sulphide had no effect, or toxicity at high doses. We previously found that, when used just prior to resuscitation in a severe haemorrhage-reperfusion injury rat model, mortality was halved. We also found benefit in a heart ischaemia-reperfusion model with a 43% reduction in damaged heart tissue. We wish to extend our findings to explore outcomes in animal models of brain ischaemia. We will focus on mechanisms associated with brain protection after TTM treatment, such as brain inflammation and cognitive performance. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001 Leishmaniasis in the Brazilian Amazon: the role of accessory microbiota in disease progression, pathobiology and immunity. Leishmania spp. infection represents a serious public health burden in Brazil, with 35,000 suspected cases annually. Disfiguring and occasionally fatal cutaneous and muco-cutaneous forms of Leishmaniasis are most common in the Amazon region of Brazil. Differential clinical severity and drug-resistance profiles are widely reported between patients. There is thus an urgent need to identify what factors might be responsible for different patient outcomes. Leishmania species and genotype have a role in defining disease severity, as does the host immune response. Less commonly considered is the role that secondary bacterial infections and commensal skin microbiota have in modulating pathology and immunity. In this multidisciplinary project we propose to use state-of-the-art techniques to monitor Leishmania lesion-associated microbial diversity and host immune response to reveal the factors that underlie cutaneous Leishmaniasis severity and progression in Amazonian Brazil. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton 001 Development of new GPCRs interacting drugs to treat inflammatory diseases The overwhelming systemic inflammatory response triggered by acute infection (sepsis) and its progression into septic shock can lead to progressive organ dysfunction. This condition has a 70-90% mortality rate and is a major public health problem both the UK and Brazil. In Brazil there has been a dramatic increase in the number of sepsis-associated deaths (9.8% in 2002 to 16.5% in 2010). A major challenge in the treatment of sepsis-induced cardiovascular collapse is the fact that it is not responsive to standard vasopressor and inotropic treatments. This situation is aggravated in populations where healthcare provision is not readily accessible, either for socio-economical or geographical reasons, leading to exacerbation of the underlying infection. The proposed work intends to exploit recent knowledge of the ability of drugs to bias responses from cell surface receptors to particular intracellular signalling pathways in order to develop inotropic and vasopressor treatments that are effective in sepsis. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Developing a policy to reduce the salt content of food consumed outside the home in Malaysia Salt intake in Malaysia is very high, with an average intake of around 9g per day. A high salt intake raises blood pressure and high blood pressure increases the risk of developing a cardiovascular disease (CVD), which includes stroke and heart disease. Almost a third of adults have high blood pressure in Malaysia and CVD is the main cause of death and disability, which places a huge burden on communities and health services. We previously assessed awareness and knowledge of salt in Malaysia. The majority of the population knew that eating too much salt could cause health problems but more than half thought they consumed just the right amount of salt. We also found that foods consumed outside the home e.g. from restaurants are major contributors of salt to the typical diet and the majority of the population eat out on a regular basis. The salt content of food consumed outside the home is likely to be very high, but without nutrition labelling consumers are unaware of the salt content. We will interview stakeholders across the country to determine what factors they feel might prevent a policy to reduce salt levels in the out of home sector and we will use this data to develop a strategy, addressing all issues raised. We will then gain commitment from policy makers to implement our strategy as policy. To ensure engagement and support for the policy, we will organise workshops to explain to chefs and other food industry representatives why salt should be reduced, and the methods they can use to reduce salt in food. Our work will benefit the entire population - almost everyone stands to benefit from a reduction in salt intake as almost everyone eats far more salt than recommended The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Genomic profiling of Cardiomyopathy in Malaysia Inherited cardiomyopathy is one of the most common causes of heart failure. The most common forms are  Hypertrophic Cardiomyopathy or HCM, which affects 1 in 500 of the population, and dilated cardiomyopathy or DCM, which affects 1 in 2500. Individuals with cardiomyopathy may not be aware of the condition until they develop complications.  To date, there is no cure for these diseases and patients are mainly treated symptomatically. Most of systematic genetic studies of HCM and DCM have focused on North American or Western European patient populations. This planned work will extend initial findings that some predominant mutations reported in Caucasians are absent in the Malaysian population and provide a comprehensive analysis of the genetic profiles of Malaysian cardiomyopathy patients. We hope the study will identify significant variants in the Malaysian population and provide valuable information to improve the clinical aspects of cardiomyopathy, including early diagnosis, prognosis and genetic counselling for affected families, in Malaysia. Overall, it will lead to improvement of the welfare of the population of Malaysia by improving the diagnosis and clinical management of cardiomyopathy in Malaysia with lasting benefits for patients and their families. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Investigating mechanistic causes of C9ORF72-related amyotrophic lateral sclerosis (ALS). Cells constitute the basic building blocks of the human body converting food and oxygen into energy to produce proteins. The blueprint for making up proteins, the DNA, is housed in the nucleus, a cell centre separated from the surrounding compartment, the cytoplasm, where proteins are assembled into the machinery supporting life. Small messenger species (messenger RNAs) copied from the blueprint are able to pass from the nucleus into the cytoplasm where each guides the building of one protein. The quantity and function of proteins account for survival or death of cells including motor neurons. Amyotrophic lateral sclerosis (ALS) is a fatal adult disease caused by progressive death of nerve cells that connect muscles to the brain and the spinal cord. This provokes gradual paralysis and death usually 3-5 years from symptom onset. There is currently no cure and the only drug available, Riluzole, has modest effect prolonging life for only approximately 3 months. Expansion of a repeated sequence in the C9ORF72 gene is the commonest alteration found in the DNA of patients with ALS. This genetic alteration causes damage to thousands of messenger species resulting in the potential malfunction of multiple aspects of the cellular machinery. However, the actual culprit(s) causing motor neuron injury have not yet been found. This project aims to identify the contribution of each potential abnormal mechanism that causes motor neuron injury in C9ORF72-related ALS, their pathological mode of action, and will help us to find biomarkers useful in diagnosis and disease monitoring. We have used cutting-edge scientific methods to produce nerve cells from healthy and C9ORF72-ALS patients' skin cells and have generated other cell models engineered for studying individually the effects of one potential mechanism of disease at a time. Using these models, we will now be able to carry out experiments aimed at understanding how decreased electrical/survival properties of nerve cells, altered content of messenger species and abnormal passage of messengers from the nucleus into the cytoplasm, occur in disease. In the future, we expect that a better understanding of the basic biological mechanisms of C9ORF72-related ALS from this study will allow the development of novel strategies for neuroprotective therapy. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Newton001 The dependency of HIV-1 and dengue virus infections on host metabolism as novel targets for antiviral therapy. Determination of the effect dengue virus infection of human liver cells on the main metabolic pathways of the cell. In particular, the modulation of the activity of glucose metabolism and respiration of human liver cells infected with dengue virus and upon expression of individual non-structural viral proteins NS1 and NS3 will be assessed in real time. In parallel, the effect on gene-expression from the same samples of liver cells will be determined. Identification of the enzymes of glucose metabolism that have altered activity in HIV-1 infected cells. By generating enzyme preparations from HIV-1 infected and uninfected white blood cells, we will determine which steps in the pathway of glucose metabolism are subject to changes in activity upon infection with HIV-1. The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Immunological tools for a seroprevalence and immune status map of Burkholderia pseudomallei and thailandensis in Vietnam This Newton Fund application seeks to enhance existing research links between immunology/microbiology researchers in Hanoi and at Imperial College London. The biomedical research question concerns appraisal in Vietnam of the risk of melioidosis. This is a potentially severe or lethal bacterial infection caused by the bacterium, Burkholderia pseudomallei, found in many temperate countries in the soil and in the water supply. The disease is associated with thousands of deaths annually in neighbouring Thailand. It has been predicted that the disease may be under-diagnosed in several other countries including Vietnam, but no comprehensive data exists. With more precise data, it would be possible to put appropriate plans in place for diagnosis and antibiotic treatment protocols. This proposal thus brings together researchers who have a strong, ongoing, interest in this question, from Hanoi and London. We plan to appraise the situation at several levels. The first is to take soil samples from sites across the country, determining distribution and load of the bacterium. As part of this work we will also assess presence of a closely related but non-pathogenic bacterium called Burkholderia thailandensis. This is important as immunity to the two bacteria is partly cross-reactive and there is a view that exposure to environmental thailandensis may protect against melioidosis. We will then work with collaborators at five regional hospitals across the country, collecting a small blood sample from 200 volunteer donors at each centre, during routine health-checks. This sample will be used to check for antibodies to the two bacteria, giving a dataset for 'seroprevalence' - that is, a regional map of human exposure to the bacteria, which can be overlaid with the mapped soil samples. This will not tell us how many people have melioidosis. Rather, it will give a picture of whether or not there are indeed regions of Vietnam similar to high-risk regions of N. Thailand, where a majority of people develop high levels of antibody after bacterial exposure. Since those people who show immunity to the bacterium but show no signs of disease must have functional protection, we will do collaborative studies to characterise the nature of this protection at the level of white blood cells termed 'T cells.' A closely related issue is that diabetes is by far the strongest risk factor for development of severe disease in individuals exposed to the bacterium. For this reason, we will use the serum samples to build a parallel, regional map of the prevalence of diabetes, believed to be growing rapidly in Vietnam. This study will include point-of-care blood glucose and analysis of pancreatic autoantibodies. A strong component of the work will be the interactive and training component, including annual workshops held in Vietnam The Newton Fund builds research and innovation partnerships with developing countries across the world to promote the economic development and social welfare of the partner countries.
Military Interdepartmental Purchase Request - USAFRICOMTraining, South Africa Military Interdepartmental Purchase Request - USAFRICOMTraining, South Africa; Undercover & Surveillance Operations Seminar
DEA Counternarcotics Training, South Africa DEA Counternarcotics Training, South Africa; Foreign counternarcotics training in Africa.
Psychische Gesundheit und psychosoziale Unterstützung (MHPSS) für syrische Flüchtlinge und Bewohnerinnen aufnehmender Ge Mental Health and Psychosocial Support (MHPSS) for Syrian Refugees and Residents of Host Communities in Turkey. MHPSS-Leistungen für syrische Flüchtlinge und BewohnerInnen aufnehmender Gemeinden in der Türkei sind gestärkt. MHPSS services for Syrian refugees and residents of host communities in Turkey are strengthened. MHPSS-Leistungen für syrische Flüchtlinge und BewohnerInnen aufnehmender Gemeinden in der Türkei sind gestärkt. MHPSS services for Syrian refugees and residents of host communities in Turkey are strengthened.