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Key Points Nanotechnology makes use of the unique properties of objects that function as a unit within the overall size range of 1 to 1,000 nanometres, which is on the same scale as for many biological structures such as antigens, receptors, subcellular components of the immune system and microbes. The engineering of nanoscale compounds by the modification of properties such as nanoparticle size, shape, charge, porosity, surface area and hydrophobicity holds great promise for the development of immune response modulators and vaccines. The enhancement of the immune response by nanoparticles can be achieved through innate immune potentiation or by the enhanced delivery of antigens. Virus-like particles activate the innate immune response via Toll-like receptors and the repetitive display of antigens, whereas nanogels and cationic liposomes are examples of vaccine carriers. The molecular pathways involved in immune activation by nanoparticles are diverse and might include the upregulation of homing receptors such as CC-chemokine receptor 7, co-stimulatory molecules including CD40, CD80 and CD86, as well as increased cytokine production. Enhanced delivery by nanoparticles might induce apoptosis or necrosis. The suppression of the immune response can be achieved through direct immunosuppression or by the delivery of immunosuppressants. Fullerenes have a direct immunosuppressive effect but can also deliver immunosuppressive drugs, as can dendrimers, polymers, and liposomes. The molecular pathways involved in immunosuppression might include increased expression of cyclooxygenase 2, prostangandin E2 and interleukin-10 (IL-10), and apoptosis. The delivery of immunosuppressants results in a decreased response to IL-2 with sirolimus, in the downregulation of nuclear factor-kB with steroids, and in the upregulation of forkhead box P3 (FOXP3), which causes an increased regulatory T cell activity when self antigens are presented. Nanotechnology will continue to provide remarkable insights into the nature of the immune response. The application of nanotechnology to immunology might also affect new strategies to prevent or to treat human diseases. This Review describes the different types of nanotechnologies that can be used to target the immune system. The authors explain how the unique properties of different nanostructures can be used to either enhance or to suppress immune responses, and they discuss the promise of these strategies for developing more effective immunotherapies. Nanotechnology uses the unique properties of objects that function as a unit within the overall size range of 1–1,000 nanometres. The engineering of nanostructure materials, including nanoparticles, nanoemulsions or nanotubules, holds great promise for the development of new immunomodulatory agents, as such nanostructures can be used to more effectively manipulate or deliver immunologically active components to target sites. Successful applications of nanotechnology in the field of immunology will enable new generations of vaccines, adjuvants and immunomodulatory drugs that aim to improve clinical outcomes in response to a range of infectious and non-infectious diseases.

The Decadal Climate Prediction Project (DCPP) is a coordinated multi-model investigation into decadal climate prediction, predictability, and variability. The DCPP makes use of past experience in simulating and predicting decadal variability and forced climate change gained from the fifth Coupled Model Intercomparison Project (CMIP5) and elsewhere. It builds on recent improvements in models, in the reanalysis of climate data, in methods of initialization and ensemble generation, and in data treatment and analysis to propose an extended comprehensive decadal prediction investigation as a contribution to CMIP6 (Eyring et al., 2016) and to the WCRP Grand Challenge on Near Term Climate Prediction (Kushnir et al., 2016). The DCPP consists of three components. Component A comprises the production and analysis of an extensive archive of retrospective forecasts to be used to assess and understand historical decadal prediction skill, as a basis for improvements in all aspects of end-to-end decadal prediction, and as a basis for forecasting on annual to decadal timescales. Component B undertakes ongoing production, analysis and dissemination of experimental quasi-real-time multi-model forecasts as a basis for potential operational forecast production. Component C involves the organization and coordination of case studies of particular climate shifts and variations, both natural and naturally forced (e.g. the \"hiatus\", volcanoes), including the study of the mechanisms that determine these behaviours. Groups are invited to participate in as many or as few of the components of the DCPP, each of which are separately prioritized, as are of interest to them.The Decadal Climate Prediction Project addresses a range of scientific issues involving the ability of the climate system to be predicted on annual to decadal timescales, the skill that is currently and potentially available, the mechanisms involved in long timescale variability, and the production of forecasts of benefit to both science and society.

Vaccine adjuvants have been reported to induce both mucosal and systemic immunity when applied to mucosal surfaces and this dual response appears important for protection against certain pathogens. Despite the potential advantages, however, no mucosal adjuvants are currently approved for human use. Evaluating compounds as mucosal adjuvants is a slow and costly process due to the need for lengthy animal immunogenicity studies. We have constructed a library of 112 intranasal adjuvant candidate formulations consisting of oil-in-water nanoemulsions that contain various cationic and nonionic surfactants. To facilitate adjuvant development we first evaluated this library in a series of high-throughput, in vitro assays for activities associated with innate and adaptive immune activation in vivo. These in vitro assays screened for the ability of the adjuvant to bind to mucin, induce cytotoxicity, facilitate antigen uptake in epithelial and dendritic cells, and activate cellular pathways. We then sought to determine how these parameters related to adjuvant activity in vivo. While the in vitro assays alone were not enough to predict the in vivo adjuvant activity completely, several interesting relationships were found with immune responses in mice. Furthermore, by varying the physicochemical properties of the surfactant components (charge, surfactant polar head size and hydrophobicity) and the surfactant blend ratio of the formulations, the strength and type of the immune response generated (TH1, TH2, TH17) could be modulated. These findings suggest the possibility of using high-throughput screens to aid in the design of custom adjuvants with unique immunological profiles to match specific mucosal vaccine applications.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb) is contracted via aerosol infection, typically affecting the lungs. Mycobacterium bovis bacillus Calmette-Guerin (BCG) is the only licensed vaccine and has variable efficacy in protecting against pulmonary TB. Additionally, chemotherapy is associated with low compliance contributing to development of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mtb. Thus, there is an urgent need for the design of more effective vaccines against TB. Experimental vaccines delivered through the mucosal route induce robust T helper type 17 (Th17)/ Interleukin (IL) -17 responses and provide superior protection against Mtb infection. Thus, the development of safe mucosal adjuvants for human use is critical. In this study, we demonstrate that nanoemulsion (NE)-based adjuvants when delivered intranasally along with Mtb specific immunodominant antigens (NE-TB vaccine) induce potent mucosal IL-17T-cell responses. Additionally, the NE-TB vaccine confers significant protection against Mtb infection, and when delivered along with BCG, is associated with decreased disease severity. These findings strongly support the development of a NE-TB vaccine as a novel, safe and effective, first-of-kind IL-17 inducing mucosal vaccine for potential use in humans.

Pathogenic variants in KCNT1 represent an important cause of treatment-resistant epilepsy, for which an effective therapy has been elusive. Reports about the effectiveness of quinidine, a candidate precision therapy, have been mixed. We sought to evaluate the treatment responsiveness of patients with KCNT1-related epilepsy. We performed an observational study of 43 patients using a collaborative KCNT1 patient registry. We assessed treatment efficacy based upon clinical seizure reduction, side effects of quinidine therapy, and variant-specific responsiveness to treatment. Quinidine treatment resulted in a > 50% seizure reduction in 20% of patients, with rare patients achieving transient seizure freedom. Multiple other therapies demonstrated some success in reducing seizure frequency, including the ketogenic diet and vigabatrin, the latter particularly in patients with epileptic spasms. Patients with the best quinidine response had variants that clustered distal to the NADP domain within the RCK2 domain of the protein. Half of patients did not receive a quinidine trial. In those who did, nearly half did not achieve therapeutic blood levels. More favorable response to quinidine in patients with KCNT1 variants distal to the NADP domain within the RCK2 domain may suggest a variant-specific response.

Nomenclature for Major Histocompatibility Complex (MHC) genes and alleles in species other than humans and mice has historically been overseen either informally by groups generating sequences, or by formal nomenclature committees set up by the International Society for Animal Genetics (ISAG). The suggestion for a Comparative MHC Nomenclature Committee was made at the ISAG meeting held in Göttingen, Germany (2002), and the committee met for the first time at the Institute for Animal Health, Compton, UK in January 2003. To publicize its activity and extend its scope, the committee organized a workshop at the International Veterinary Immunology Symposium (IVIS) in Quebec (2004) where it was decided to affiliate with the Veterinary Immunology Committee (VIC) of the International Union of Immunological Societies (IUIS). The goals of the committee are to establish a common framework and guidelines for MHC nomenclature in any species; to demonstrate this in the form of a database that will ensure that in the future, researchers can easily access a source of validated MHC sequences for any species; to facilitate discussion on this area between existing groups and nomenclature committees. A further meeting of the committee was held in September 2005 in Glasgow, UK. This was attended by most of the existing committee members with some additional invited participants (Table 1). The aims of this meeting were to facilitate the inclusion of new species onto the database, to discuss extension, improvement and funding of the database, and to address a number of nomenclature issues raised at the previous workshop.

Status epilepticus is a common pediatric neurological emergency. Management includes prompt administration of appropriately selected anti-seizure medications, identification and treatment of seizure precipitant(s), as well as identification and management of associated systemic complications. This review discusses the definitions, classification, epidemiology and management of status epilepticus and refractory status epilepticus in children.

Resource herds of swine leukocyte antigen (SLA)-characterized pigs are an important tool for the study of immune responses, disease resistance, and production traits. They are also valuable large animal models for biomedical research, such as transplantation. The Meishan breed of pig is an economically significant breed that is available at several research institutions in the United States. We have characterized the SLA polymorphism of the breeding stock in the herd maintained at the University of Illinois and developed a simple assay to SLA type individuals within that herd. We have used a reverse transcription-polymerase chain reaction (RT-PCR)-based SLA typing method to clone and DNA sequence 19 SLA alleles at three SLA class Ia (SLA-1, SLA-2, and SLA-3) and two SLA class II (SLA-DRB1 and SLA-DQB1) loci. Based on this sequence information, a rapid SLA typing assay was developed to discriminate each allele using PCR with sequence-specific primers (PCR-SSP). Using this method, we were able to characterize the entire Meishan breeding stock and identify four SLA haplotypes present in the herd. The combination of SLA typing by cloning and DNA sequencing with PCR-SSP is therefore a valuable tool for the characterization of SLA alleles and haplotypes in resource herds of pigs.

The highly polymorphic porcine major histocompatibility complex (MHC), or the swine leukocyte antigens (SLA), has been repeatedly associated with variations in swine immune response to pathogens and vaccines as well as with production traits. The SLA antigens are also important targets for immunological recognition of foreign tissue grafts. We recently established a resource population of Korean native pigs as models for human transplantation and xenotransplantation research. In this study, 115 animals derived from three generations of the Korean native pigs were genotyped for three SLA class Ⅰ (SLA-2, SLA-3 and SLA-1) and three SLA class Ⅱ loci (DRB1, DQB1, DQA) using PCR with sequence-specific primers (PCR-SSP) at the allele group resolution. A total of seven SLA haplotypes (Lr-5.34, Lr-7.23, Lr-31.13, Lr-56.23, Lr-56.30, Lr-59.1, Lr-65.34), comprising six unique class Ⅰ and five unique class Ⅱ haplotypes, were characterized in the founding animals. Class Ⅰ haplotype Lr-65.0 and class Ⅱ haplotype Lr-0.34 were novel; and together with Lr-56.0 these haplotypes appeared to be breed-specific. In the progeny population, Lr-7.23 and Lr-56.30 appeared to be the most prevalent haplotypes with frequencies of 34.7% and 31.6%, respectively; the overall homozygosity was 27.4%. This resource population of SLA-defined Korean native pigs will be useful as large animal models for various transplantation and xenotransplantation experiments, as well as for dissecting the roles of SLA proteins in swine disease resistance and production traits.