Irrational use of antibiotics is a serious issue globally. It is also very common among children with acute upper respiratory tract infection (URTI). It left many children suffering from the bacterial resistance due to irrational use of antibiotics, especially in less developed rural area. Antibiotic widely abused in China, more severe in rural areas. However, few studies focused on this area in developing countries including China. We intend to carry out a feasibility study rural Guangxi, China to explore an effective approach of reducing irrational antibiotic prescription for upper respiratory infections (URTIs) among children. To define the facilitators and barriers that influence antibiotic prescribing for childhood URIs in rural Guangxi, questionnaire will be used to interview policy makers from provincial, county Bureau of Health and leaders from township hospital. We will also interview these policy-makers, clinicians and caregivers to obtain their perspective opinions regarding rational antibiotic use. Then the theory based intervention package, which had been developed in Bangladesh and tested in Zhejiang province, will be evaluated in rural Guangxi once adapted further to be sensitive to the local context. Finally the intervention package will then be tested in 6 townships within one county. Six township hospitals will be divided into three groups. The arm A will be only targeted clinicians, with: operational guidelines and training on rational antibiotic use, mobile message reminder from pharmacist). Group B will be involving both clinicians and caregivers , which will include: the leaflet material and video information on rational antibiotic use, workshops between parents/caregivers and the trained kindergarten volunteers. The usual-care control group C will manage patients according to the clinicians' normal procedures without any intervention. We will carry out the intervention for 6 months and collect inpatient and outpatient prescriptions for 6 months before and after interventions. A questionnaire survey will be conducted to see the changes among clinicians, caregivers and kindergarten teachers' knowledge, attitude and practice (KAP) before and after intervention at each group. Interview and group discussion will be used to see if this study is feasible and acceptable with the intervention package. Also positive and negative factors for the intervention implementation will be carried out. We will assess effectiveness though the difference in the antibiotic prescriptions rate among all the prescriptions between before and after intervention and between intervention and control groups. Those preliminary data will help us to aid in planning a larger effectiveness study in whole Guangxi province.

Dimethylsulfide (DMS) is a key ingredient in the cocktail of gases that makes up the 'smell of the sea'. Around 300 million tons of DMS are formed each year by single-celled organisms in the surface ocean. A small proportion (up to 16%) of this DMS is released into the atmosphere, forming cloud-seeding compounds which can influence our weather and climate. When it rains, sulfur compounds are deposited back into the soils of our continents. However, most of the DMS formed in the oceans stays there, facing consumption by marine microbes and conversion to another sulfur compound - dimethylsulfoxide (DMSO). DMSO is usually the most abundant organic sulfur compound in the oceans and represents a major pool of the essential life elements sulfur and carbon. Seawater contains a rich mixture of important chemical nutrients that support the entire oceanic food web. The dissolved organic nitrogen pool is a chemical 'drive thru' which contains the highly reactive N-osmolytes: glycine betaine, choline and trimethylamine N-oxide. These chemicals are used by microorganisms to protect them from changes in their environmental conditions, such as variability in the saltiness of the surrounding seawater, and to protect their cells from chemical or physical damage. When N-osmolytes breakdown they can release gases such as methylamines into the atmosphere which can influence the climate. We have found a previously unrecognised and intriguing link between the bacterial breakdown of organic nitrogen compounds, like methylamines, and organic sulfur compounds like DMS. This link is provided by a bacterial enzyme called trimethylamine monooxygenase (Tmm). Tmm simultaneously removes both methylamines and DMS from seawater (converting it to DMSO). In fact we think this production of DMSO doesn't happen without the presence of methylamines. We estimate that up to 20% of all bacteria in our oceans contain this particular enzyme. The research we want to carry out will firstly investigate this link between DMS removal and methylamine availability in 'model' micro-organisms in the laboratory, checking that this link is active and how it is controlled in key marine bacteria commonly found in the global oceans. We will next determine the importance of this process compared to other biological processes that consume DMS in seawater and put names to the microbes using this enzyme to remove DMS. We will study the microbial processes linking the organic sulfur and nitrogen cycles in the English Channel at a station that is sampled weekly as part of the Western Channel Observatory which is coordinated by Plymouth Marine Laboratory. This is a long-standing time series site for which a wealth of oceanographic and biological data are available (algal diversity, temperature, nutrients etc.; http://www.westernchannelobservatory.org.uk), which we will be able to use. A global model of particles in the atmosphere has recently suggested that changes in the location of DMS emissions, through climate-driven changes in the phytoplankton species distributions, could strongly influence our climate. We therefore want to investigate the link between DMS removal, the availability of organic nitrogen compounds like methylamines and phytoplankton species, which we can do at station L4, where phytoplankton species succession is understood and can be easily sampled. We will compare this temperate coastal region to one of the Earth's DMS hotspots - the Southern Ocean. The atmosphere above this remote and isolated ocean is pristine in comparison to the heavily polluted air of the Northern Hemisphere. Here, the connection between DMS produced in the oceans and our climate is thought to be the strongest. Given the important role of DMS, identifying the role of marine microorganisms and the pathways of DMS removal from seawater will provide key information that will improve our future understanding of how the sulfur cycle influences our climate.

A billion tonnes of the compatible solute dimethylsulfoniopropionate (DMSP) is made each year by marine phytoplankton, seaweeds, corals, coastal plants and, as shown by us, marine bacteria. DMSP has key roles in marine ecosystems when released into the environment, serving as an osmoprotectant and key nutrient for marine microbial communities. DMSP is also the main precursor of the climate-cooling gas dimethylsulfide (DMS). Many organisms cleave DMSP, producing ~300 million tonnes of DMS annually, ~10 % of which is released into the air. DMS oxidises in the atmosphere, producing aerosols that can lead to increased cloud cover and potential effects on climate, or be returned to land in rain, a key step in the global sulfur cycle. DMSP and DMS are also chemoattractants for many organisms which associate them with food. Despite the importance of DMSP, knowledge of how and why it is produced is quite superficial. We know that DMSP and DMS production is highly variable between and within the different groups of producers, but the reasons for this variability are not understood, mainly because genes encoding DMSP synthesis enzymes have yet to be identified and DMSP lyases have only just been identified in a DMSP-producing organism. Our preliminary work has identified dsy genes which encode key DMSP synthesis enzymes in bacteria, diatoms, dinoflagellates, corals and haptophytes - the major groups of marine DMSP-producers. Variability in DMSP/DMS production may stem from their different Dsy enzymes. Our aim is to establish "why some organisms make more DMSP than others and the contribution of different organisms to global DMSP and DMS production". It is possible that variability in DMSP production in different organisms stems from the differing efficiencies or expression of their Dsy enzymes. To test this, we will use biochemical techniques to characterise the different Dsy enzymes of the major classes of DMSP-producers. We will study how diverse, model DMSP-producers express their DMSP and DMS synthesis enzymes in response to varying conditions, since the expression level may govern the amount of DMSP produced. This may shed light on the effects of climate change, e.g., if Dsy and DMSP lyase expression is increased by higher temperatures. For the important DMSP/DMS-producing algae Emiliania huxleyi and Symbiodinium, we will precisely locate the Dsy enzymes within the cell as this will help in understanding the role(s) of DMSP in these organisms. By relating cellular location and Dsy enzymology data to DMSP (and synthesis intermediates) and DMS concentrations, production rates in key DMSP producers and the conditions that enhance accumulation, we will more fully understand why high variability in DMSP and DMS production exists. As future changes in environmental conditions will likely affect DMSP/DMS production, and potentially climate, and vice versa, it is important to understand and predict these effects. Current estimates of DMSP/DMS production are likely inaccurate due to a lack of integrated studies combining molecular, biogeochemical, process and modelling data. Here, we will carry out a detailed, year-long study at the coastal site L4 in the English Channel (chosen for its location and range of contextual data). We will study the diversity and expression of key genes in DMSP/DMS synthesis, DMSP synthesis rates, group-specific phytoplankton DMSP production, bulk standing stocks of DMSP (and synthesis intermediates) and DMS and microbial diversity over a seasonal succession. Our studies will tell us which organisms produce DMSP/DMS, production rates and concentrations, the genes used and under what conditions. Using these data, we will input critical state and rate parameters into a new model for DMSP/DMS dynamics, allowing the contribution of different taxa to global production of DMSP/DMS to be more accurately predicted, along with any possible effects of climate change.

Marine-dwelling microbes and plants produce 8 billion tonnes of dimethylsulfoniopropionate (DMSP) per year in Earth's surface oceans alone, via enzymes we have identified. Organisms produce DMSP to protect against salinity, cold, turgor pressure, oxidative and drought stresses, and predation. DMSP released into the environment is also widely taken up by microbes for these anti-stress properties, and used as a key nutrient via distinct degradation pathways. DMSP has critically important roles in global sulfur and carbon cycling, signalling, and as a major source of climate-active gases (CAG) e.g. dimethylsulfide (DMS) and the foul-smelling gas methanethiol (MeSH). Each year millions of tonnes of DMS, the characteristic smell of the seaside and a potent foraging cue guiding diverse organisms (gulls, seals, zooplankton, etc) to food, is released from DMSP via microbial DMSP lyase enzymes that we also identified. Some DMS is released and oxidised to form aerosols and cloud condensation nuclei in the atmosphere, which reduce the global radiation budget and 'cool' local climate. Critically, these sulfate aerosols return to land in rain - the primary transfer of biogenic sulfur from the oceans to land. DMSP synthesis and degradation are thought to occur only in marine settings, so DMSP cycling in terrestrial environments has largely been unexplored. We challenged this dogma by revealing that DMSP synthesis is widespread in the plant Kingdom, ranging from common plants like grass, to agriculturally-important crops like maize, cabbage and sugarcane. Furthermore, our preliminary work shows that DMSP levels surpassing those in seawater exist in soils in which these key agricultural and bioenergy crops grow. Our work shows such soils liberate significant quantities of DMS and MeSH - processes ignored in climate models. We have also isolated novel bacteria and fungi from maize and sugarcane soils that utilise DMSP as a carbon source and show inducible DMSP-dependent DMS or MeSH production. Critically, these bacteria lack known DMSP degradation genes in their genomes, and thus likely possess novel DMSP catabolic enzymes and/or pathways. We have therefore uncovered a potentially large and virtually unexplored research area with profound implications for biogeochemical cycling. Our findings urgently require detailed study to establish the importance and influence of terrestrial DMSP cycling on the climate. We wish to answer the fundamentally important questions of how microbes associated to terrestrial plants degrade DMSP, and the ecological and global importance of the process, especially relating to CAG production. We will test the hypothesis that plant-made DMSP is a key nutrient for CAG-producing microbes. In an everyday context, are microbes degrading DMSP responsible for the rotten MeSH smell associated with cabbage fields, or the sweet DMS smell associated with sweetcorn? We will study microbial DMSP degradation and concomitant CAG production associated to plants known to produce low (maize) and high (sugarcane) levels of DMSP, which together cover >0.2 billion ha. Collaborations are in place to sample these plants, as are the model DMSP-producing bacteria we isolated to study microbial DMSP degradation mechanisms in terrestrial environments. Our major aims are to elucidate the enzymes, pathways, and mechanisms of DMSP degradation in terrestrial microbes and use this knowledge to define the magnitude of the process and factors regulating it. Furthermore, we will use cutting-edge microbial ecology, modelling and process work to answer fundamental ecological questions: what are the key microbes that degrade DMSP and emit CAG in terrestrial environments, and how do they influence the climate? We see our proposal as addressing a major new challenge that will reveal the importance of DMSP in terrestrial environments, uncovering new and unexpected research fields with far-reaching implications for current and future climate models.