Towards a greater engagement of universities in addressing climate change challenges.

Many higher education institutions around the world are engaged in efforts to tackle climate change. This takes place by not only reducing their own carbon footprint but also by educating future leaders and contributing valuable research and expertise to the global effort to combat climate change. However, there is a need for studies that identify the nature of their engagement on the topic, and the extent to which they are contributing towards addressing the many problems associated with climate change. Against this background, this paper describes a study that consisted of a review of the literature and the use of case studies, which outline the importance of university engagement in climate change and describe its main features. The study identified the fact that even though climate change is a matter of great relevance to universities, its coverage in university programmes is not as wide as one could expect. Based on the findings, the paper also lists the challenges associated with the inclusion of climate change in university programmes. Finally, it describes some of the measures which may be deployed in order to maximise the contribution of higher education towards handling the challenges associated with a changing climate.

Intestinal Barrier and Gut Microbiota in Patients with Overlapping Irritable Bowel Syndrome and Functional Dyspepsia.

BACKGROUND: Disturbances in the intestinal barrier and gut dysbiosis have been observed in patients with functional bowel diseases. AIMS: To investigate the correlation between biomarkers of intestinal barrier disorders at different layers and the severity of symptoms in patients with overlapping diarrhea-predominant irritable bowel syndrome and functional dyspepsia (IDFO), as well as with gut microbiota taxa. METHODS: This study included 45 patients with IDFO and 16 healthy controls. Endoscopy with biopsy of the duodenum and sigmoid colon (SC) was performed to count intraepithelial lymphocytes (IELs) and mucosal eosinophils (subepithelial layer), assess fatty acid binding protein (FABP; epithelial layer) level, and stain for mucin-2 (MUC-2; pre-epithelial layer). Composition of the gut microbiota was evaluated using 16S rRNA gene sequencing. RESULTS: Patients with IDFO exhibited an increase in biomarkers of intestinal barrier disorders at all layers studied. IEL count in the duodenum was correlated with the severity of bloating (r = 0.336; p = 0.024) and, in the SC, was correlated with tenesmus severity (r = 0.303; p = 0.042). FABP-1 level in the SC was correlated with the severity of diarrhea (r = 0.577; p = 0.001), and FABP-5 concentration in the SC was correlated with abdominal distension (r = 0.477; p = 0.010). MUC-2 concentration in the duodenum was correlated with the severity of heartburn (r = 0.572; p = 0.025) and burning sensation in the epigastrium (r = 0.518; p = 0.048). All biomarkers of intestinal barrier permeability were correlated with the abundance of some gut microbiota taxa. CONCLUSION: Patients with IDFO exhibited disrupted intestinal barrier function in all layers, which was associated with clinical symptom severity and changes in the gut microbiota.

Estimation of cardiorespiratory fitness using heart rate and step count data.

Predicting cardiorespiratory fitness levels can be useful for measuring progress in an exercise program as well as for stratifying cardiovascular risk in asymptomatic adults. This study proposes a model to predict fitness level in terms of maximal oxygen uptake using anthropometric, heart rate, and step count data. The model was trained on a diverse cohort of 3115 healthy subjects (1035 women and 2080 men) aged 42 ± 10.6 years and tested on a cohort of 779 healthy subjects (260 women and 519 men) aged 42 ± 10.18 years. The developed model is capable of making accurate and reliable predictions with the average test set error of 3.946 ml/kg/min. The maximal oxygen uptake labels were obtained using wearable devices (Apple Watch and Garmin) during recorded workout sessions. Additionally, the model was validated on a sample of 10 subjects with maximal oxygen uptake determined directly using a treadmill protocol in a laboratory setting and showed an error of 4.982 ml/kg/min. Unlike most other models, which use accelerometer readings as additional input data, the proposed model relies solely on heart rate and step counts-data readily available on the majority of fitness trackers. The proposed model provides a point estimation and a probabilistic prediction of cardiorespiratory fitness level, thus it can estimate the prediction's uncertainty and construct confidence intervals.

Effect of Rebamipide on the Intestinal Barrier, Gut Microbiota Structure and Function, and Symptom Severity Associated with Irritable Bowel Syndrome and Functional Dyspepsia Overlap: A Randomized Controlled Trial.

Treatment of functional digestive disorders is not always effective. Therefore, a search for new application points for potential drugs is perspective. Our aim is to evaluate the effect of rebamipide on symptom severity, intestinal barrier status, and intestinal microbiota composition and function in patients with diarrheal variant of irritable bowel syndrome overlapping with functional dyspepsia (D-IBSoFD). Sixty patients were randomized to receive trimebutine (TRI group), trimebutine + rebamipide (T + R group), or rebamipide (REB group) for 2 months. At the beginning and end of the study, patients were assessed for general health (SF-36), severity of digestive symptoms (Gastrointestinal Symptom Rating and 7 × 7 scales), state of the intestinal barrier, and composition (16S rRNA gene sequencing) and function (short-chain fatty acid fecal content) of the gut microbiota. The severity of most digestive symptoms was reduced in the REB and T + R groups to levels similar to that observed in the TRI group. The duodenal and sigmoidal lymphocytic and sigmoidal eosinophilic infiltration was decreased only in the REB and T + R groups, not in the TRI group. Serum zonulin levels were significantly decreased only in the REB group. A decrease in intraepithelial lymphocytic infiltration in the duodenum correlated with a decrease in the severity of rumbling and flatulence, while a decrease in infiltration within the sigmoid colon correlated with improved stool consistency and decreased severity of the sensation of incomplete bowel emptying. In conclusion, rebamipide improves the intestinal barrier condition and symptoms in D-IBSoFD. The rebamipide effects are not inferior to those of trimebutine.

Mitochondrial ATP Synthase and Mild Uncoupling by Butyl Ester of Rhodamine 19, C4R1.

The homeostasis of the transmembrane potential of hydrogen ions in mitochondria is a prerequisite for the normal mitochondrial functioning. However, in different pathological conditions it is advisable to slightly reduce the membrane potential, while maintaining it at levels sufficient to produce ATP that will ensure the normal functioning of the cell. A number of chemical agents have been found to provide mild uncoupling; however, natural proteins residing in mitochondrial membrane can carry this mission, such as proteins from the UCP family, an adenine nucleotide translocator and a dicarboxylate carrier. In this study, we demonstrated that the butyl ester of rhodamine 19, C4R1, binds to the components of the mitochondrial ATP synthase complex due to electrostatic interaction and has a good uncoupling effect. The more hydrophobic derivative C12R1 binds poorly to mitochondria with less uncoupling activity. Mass spectrometry confirmed that C4R1 binds to the ß-subunit of mitochondrial ATP synthase and based on molecular docking, a C4R1 binding model was constructed suggesting the binding site on the interface between the α- and ß-subunits, close to the anionic amino acid residues of the ß-subunit. The association of the uncoupling effect with binding suggests that the ATP synthase complex can provide induced uncoupling.

Sustainable development goal 13 and switching priorities: addressing climate change in the context of pandemic recovery efforts.

The COVID-19 pandemic has had many deep social and economic impacts that go beyond health issues. One consequence is that the pandemic has made it even harder to mobilize the financial resources needed to pursue SDG 13 (Climate Action) as a whole and to fund climate change mitigation and adaptation efforts in particular. This is especially acute in respect of the efforts to achieve the targets set by the Paris Agreement and by the recent decisions in Glasgow. This paper looks at how the COVID-19 pandemic has accelerated poverty and undermined climate change mitigation and adaptation efforts, as a result of the switches in priorities and funding. Using a review of the recent literature, an analysis of international trends, and a survey among climate scientists, it identifies some of the impacts of the pandemic on climate change mitigation and adaptation efforts and discusses their implications. The findings indicate a decrease in funding to climate change research since the pandemic crisis. The bibliometric analysis reveals that a greater emphasis has been placed on the relationship between COVID-19 and poverty when compared to the interrelations between COVID-19 and climate change. Addressing climate change is as urgent now as it was before the pandemic crisis started, and efforts need to be made to upkeep the levels of funding needed to support research in this field.

Climate change adaptation responses among riparian settlements: A case study from Bangladesh.

As transition areas between aquatic ecosystems and the adjacent terrestrial ones, riparian regions are highly exposed to coastal climate hazards. This article describes how climate change and extreme weather impact vulnerable riparian communities and settlements. The analysis is done by reviewing past research and empirical case studies from riparian rural communities of the impact zone of the Sundarbans in Bangladesh, the world's most extensive mangrove forest. The article discusses the climate-related impacts on households through a Severity Index of Vulnerability and assesses the adaptation responses they may pursue. The principal climate-related vulnerabilities and impacts due to increases in temperature, storm surges, sea flooding, and sea-level rise are seawater intrusion and riverbank erosion. Many households have adopted several autonomous reactive adaptation strategies rather than planned ones, to cope with these impacts. However, government organisations and NGOs provide less than optimal technical and financial support to households for planned and anticipatory adaptive responses. The main barriers to adaptation were the high cost of improved crop varieties, inadequate agricultural extension services, and a lack of knowledge on effective climate adaptation. The restoration of the mangrove ecosystem may increase its resilience and, among other things, make local communities less exposed. The article also presents some adaptation measures proper to reduce the climate-related vulnerability of riparian settlements.

Thickness Effects on the Martensite Transformations and Mechanical Properties of Nanocrystalline NiTi Wires.

This paper studied the features of the martensitic transformations and mechanical properties of 40, 60, and 90 µm thick NiTi wires with nanocrystalline B2 structures. It was established that the wires were composites and consisted of a TiNi matrix and a TiO2 + TiNi3 surface layer. Structural methods showed that the wire matrix was formed by grains of up to 20 nm in size. The method of measuring the electrical resistivity during cooling and heating revealed a two-stage nature of the martensitic transformation. Cyclic loading-unloading demonstrated that all the samples exhibited superelasticity effects and completely restored their shape when unloaded from a 4-8% relative strain at room temperature. An increase in mechanical characteristics with respect to the wire thickness was experimentally established. This was due to the change in the composition of the TiNi matrix during drawing.

NiB-CrC Coatings Prepared by Magnetron Sputtering Using Composite Ceramic NiCr-BC Target Produced by Detonation Spray Coating.

A metal-ceramic composite target for magnetron sputtering was fabricated for the first time by a robotic complex for the detonation spraying of coatings equipped with a multi-chamber detonation accelerator. A mixture of metal and ceramic NiCr/B4C powders was sprayed onto the copper base of the cylindrical composite target cathode. The study of the structure of a metal-ceramic composite coating target using scanning electron microscopy showed that the coating material is dense without visible pores; the elemental composition is evenly distributed in the material. The study of the cathode sputtering area after deposition in the DC mode showed that there are uniform traces of annular erosion on the target surface. The obtained cathode target with an NiCr-70B4C coating was used to deposit the NiB-Cr7C3 coating on flat specimens of 65G steel using equipment for magnetron sputtering UNICOAT 200. The coating was applied in the Direct Current mode. A dense NiB-Cr7C3 coating with a thickness of 2 µm was obtained. The NiB-Cr7C3 coating has a quasi-amorphous structure. The microstructures and concentration of oxygen and carbon impurities throughout the entire thickness of the coating were investigated by means of transmission electron microscopy. The results of the study show that the coatings have a nanocrystalline multi-phase structure. The microhardness of the NiB-Cr7C3 coating reached 10 GPa, and the adhesion fracture load exceeded 16 N. The results will open up new prospects for the further elaboration of technology for obtaining original composite cathodes for magnetron sputtering using detonation spraying of coatings.

Promoting gender equality across the sustainable development goals.

Gender issues, and gender equality in particular, can be regarded as cross-cutting issues in the implementation of the Sustainable Development Goals (SDGs), even though it is unclear how they are taken into account. This study addresses this information gap by performing an assessment of the emphasis on gender issues across all the other 16 SDGs, in addition to SDG5, through a literature review and case study analysis, the basis for the newly developed framework, highlighting specific actions associated to each SDG. The 13 countries addressed in the 16 case studies include China, India, or Australia and illustrate the inclusion of SDG5 into the SDGs. Using an SDG matrix, the SDG targets are analysed. Those where an emphasis on gender equality is important in allowing them to be achieved are listed. The novelty of our approach resides in offering an in-depth analysis of how gender issues interact with the other SDGs, proposing a new analysis framework clearly identifying SDGs 1, 4, 11, 12, 14 and 16 demanding further attention for successful SD gender implementation and illustrating specific areas where further actions may be necessary, which may be used by policy-makers, raising further awareness on gender equality contribution to achieve the SDGs. A set of recommendations aimed at placing gender matters more centrally in the SDGs delivery are presented as a final contribution. These focus on the need for greater awareness and attention to good practices, to achieve successful implementation initiatives. Supplementary Information: The online version contains supplementary material available at 10.1007/s10668-022-02656-1.

Overview, Generation, and Significance of Variable New Antigen Receptors (VNARs) as a Platform for Drug and Diagnostic Development.

The approval of the first VHH-based drug caplacizumab (anti-von Willebrand factor) has validated a two-decade long commitment in time and research effort to realize the clinical potential of single-domain antibodies. The variable domain (VNAR) of the immunoglobulin new antigen receptor (IgNAR) found in sharks provides an alternative small binding domain to conventional monoclonal antibodies and their fragments and heavy-chain antibody-derived VHHs. Evolutionarily distinct from mammalian antibody variable domains, VNARs have enhanced thermostability and unusual convex paratopes. This predisposition to bind cryptic and recessed epitopes has facilitated both the targeting of new antigens and new (neutralizing) epitopes on existing antigens. Together these unique properties position the VNAR platform as an alternative non-antibody binding domain for therapeutic drug, diagnostic and reagent development. In this introductory chapter, we highlight recent VNAR advancements that further underline the exciting potential of this discovery platform.

Climate Change and Zoonoses: A Review of Concepts, Definitions, and Bibliometrics.

Climate change can have a complex impact that also influences human and animal health. For example, climate change alters the conditions for pathogens and vectors of zoonotic diseases. Signs of this are the increasing spread of the West Nile and Usutu viruses and the establishment of new vector species, such as specific mosquito and tick species, in Europe and other parts of the world. With these changes come new challenges for maintaining human and animal health. This paper reports on an analysis of the literature focused on a bibliometric analysis of the Scopus database and VOSviewer software for creating visualization maps which identifies the zoonotic health risks for humans and animals caused by climate change. The sources retained for the analysis totaled 428 and different thresholds (N) were established for each item varying from N 5 to 10. The main findings are as follows: First, published documents increased in 2009-2015 peaking in 2020. Second, the primary sources have changed since 2018, partly attributable to the increase in human health concerns due to human-to-human transmission. Third, the USA, the UK, Canada, Australia, Italy, and Germany perform most zoonosis research. For instance, sixty documents and only 17 countries analyzed for co-authorship analysis met the threshold led by the USA; the top four author keywords were "climate change", "zoonosis", "epidemiology", and "one health;" the USA, the UK, Germany, and Spain led the link strength (inter-collaboration); the author keywords showed that 37 out of the 1023 keywords met the threshold, and the authors' keyword's largest node of the bibliometric map contains the following: infectious diseases, emerging diseases, disease ecology, one health, surveillance, transmission, and wildlife. Finally, zoonotic diseases, which were documented in the literature in the past, have evolved, especially during the years 2010-2015, as evidenced by the sharp augmentation of publications addressing ad-hoc events and peaking in 2020 with the COVID-19 outbreak.

Mechanisms of SARS-CoV-2 neutralization by shark variable new antigen receptors elucidated through X-ray crystallography.

Single-domain Variable New Antigen Receptors (VNARs) from the immune system of sharks are the smallest naturally occurring binding domains found in nature. Possessing flexible paratopes that can recognize protein motifs inaccessible to classical antibodies, VNARs have yet to be exploited for the development of SARS-CoV-2 therapeutics. Here, we detail the identification of a series of VNARs from a VNAR phage display library screened against the SARS-CoV-2 receptor binding domain (RBD). The ability of the VNARs to neutralize pseudotype and authentic live SARS-CoV-2 virus rivalled or exceeded that of full-length immunoglobulins and other single-domain antibodies. Crystallographic analysis of two VNARs found that they recognized separate epitopes on the RBD and had distinctly different mechanisms of virus neutralization unique to VNARs. Structural and biochemical data suggest that VNARs would be effective therapeutic agents against emerging SARS-CoV-2 mutants, including the Delta variant, and coronaviruses across multiple phylogenetic lineages. This study highlights the utility of VNARs as effective therapeutics against coronaviruses and may serve as a critical milestone for nearing a paradigm shift of the greater biologic landscape.

Non-Alcoholic Steatohepatitis (NASH) - A Review of a Crowded Clinical Landscape, Driven by a Complex Disease.

Non-alcoholic steatohepatitis (NASH) is a progressive form of non-alcoholic fatty liver disease (NAFLD), characterized by chronic inflammation and accumulation of fat in liver tissue. Affecting estimated 35 million people globally, NASH is the most common chronic liver condition in Western populations, and with patient numbers growing rapidly, the market for NASH therapy is projected to rise to $27.2 B in 2029. Despite this clinical need and attractive commercial opportunity, there are no Food and Drug Administration (FDA)-approved therapies specifically for this disease. Many have tried and unfortunately failed to find a drug, or drug combination, capable of unravelling the complexities of this metabolic condition. At the time of writing this review, only Zydus Cadila's new drug application for Saroglitazar had been approved (2020) for NASH therapy in India. However, it is hoped that this dearth of therapy options will improve as several drug candidates progress through late-stage clinical development. Obeticholic acid (Intercept Pharmaceuticals), Cenicriviroc (Allergan), Aramchol (Galmed Pharmaceuticals), Resmetirom (Madrigal Pharmaceuticals), Dapagliflozin and Semaglutide (Novo Nordisk) are in advanced Phase 3 clinical trials, while Belapectin (Galectin Therapeutics), MSDC-0602K (Cirius Therapeutics), Lanifibranor (Inventiva), Efruxifermin (Akero) and Tesamorelin (Theratechnologies) are expected to start Phase 3 trials soon. Here, we have performed an exhaustive review of the current therapeutic landscape for this disease and compared, in some detail, the fortunes of different drug classes (biologics vs small molecules) and target molecules. Given the complex pathophysiology of NASH, the use of drug combination, different mechanisms of actions and the targeting of each stage of the disease will likely be required. Hence, the development of a single therapy for NASH seems challenging and unlikely, despite the plethora of later stage trials due to report. We therefore predict that clinical, patient and company interest in pipeline and next-generation therapies will remain high for some time to come.

In Vitro Maturation of a Humanized Shark VNAR Domain to Improve Its Biophysical Properties.

VNAR domains are the binding regions of new antigen receptor proteins (IgNAR) which are unique to sharks, skates, and rays (Elasmobranchii). Individual VNAR domains can bind antigens independently and are the smallest reported adaptive immune recognition entities in the vertebrate kingdom. Sharing limited sequence homology with human immunoglobulin domains, their development and use as biotherapeutic agents require that they be humanized to minimize their potential immunogenicity. Efforts to humanize a human serum albumin (HSA)-specific VNAR, E06, resulted in protein molecules that initially had undesirable biophysical properties or reduced affinity for cognate antigen. Two lead humanized anti-HSA clones, v1.10 and v2.4, were subjected to a process of random mutagenesis using error-prone PCR. The mutated sequences for each humanized VNAR variant were screened for improvements in affinity for HSA and biophysical properties, achieved without a predicted increase in overall immunogenicity.

Heading towards an unsustainable world: some of the implications of not achieving the SDGs.

The Sustainable Development Goals (SDGs) were conceived at the United Nations Conference on Sustainable Development, held in Rio de Janeiro in 2012 (Rio + 20), and adopted by the United Nations General Assembly in September 2015. They are part of a larger framework, namely the UN 2030 Agenda for Sustainable Development. Since then, many countries round the world have been engaging in respect of their implementation. The slow progress seen in the implementation of the SDGs, is in contrast with the many negative implications of not implementing them. This paper outlines the relevance of the SDGs, the barriers currently seen in respect of their implementation and outlines what is at stake, if they are not duly implemented. To accomplish this, a thorough literature review of contributions published in the field of SDGs in English between the years 2012-2020 was performed.

Uveitis Therapy With Shark Variable Novel Antigen Receptor Domains Targeting Tumor Necrosis Factor Alpha or Inducible T-Cell Costimulatory Ligand.

PURPOSE: We assess the efficacy of two next-generation biologic therapies in treating experimental autoimmune uveitis. METHODS: Variable binding domains from shark immunoglobulin novel antigen receptors (VNARs) were fused with a mouse IgG2a constant domain (Fc) to generate VNAR-Fc molecules with binding specificity to tumor necrosis factor alpha (TNFα) or inducible T-cell costimulatory ligand (ICOSL). Treatment with VNAR-Fc fusion proteins was compared to treatment with dexamethasone or vehicle in the Lewis rat model of experimental autoimmune uveitis (EAU). Inflammation control was determined by comparing OCT clinical and histologic scores, and aqueous humor protein concentration. The concentration of 27 inflammatory cytokines in the aqueous humor was measured using a multiplex enzyme-linked immunosorbent assay platform. RESULTS: Administration of S17-Fc significantly decreased clinical, histologic, and aqueous protein levels when compared to vehicle treatment. Inflammation scores and aqueous protein levels in A5-Fc-treated animals were decreased compared to vehicle treatment, but not significantly. The concentration of vascular endothelial growth factor (VEGF), regulated on activation, normal T cell expressed and secreted (RANTES), macrophage inflammatory protein 1 alpha (MIP-1α), interleukin (IL)-1ß, LPS-induced CXC chemokine (LIX), monocyte chemoattractant protein-1 (MCP-1), and interferon (IFN)-γ were significantly decreased in the eyes of animals treated with dexamethasone. VNAR treatment demonstrated a trend towards decreased cytokine concentrations, but only VEGF and RANTES were significantly decreased by S17-Fc. CONCLUSIONS: Treatment with the anti-TNFα VNAR S17-Fc ameliorates EAU as effectively as treatment with corticosteroids. TRANSLATIONAL RELEVANCE: VNAR-Fc molecules are a next-generation therapeutic biologic that overcome the limitations of classical biologic monoclonal antibodies, such as complex structure, large size, and limited tissue penetration. This is a novel drug modality that could result in the development of new therapy options for patients with noninfectious uveitis.

Heterogeneous Nuclear Ribonucleoproteins Involved in the Functioning of Telomeres in Malignant Cells.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are structurally and functionally distinct proteins containing specific domains and motifs that enable the proteins to bind certain nucleotide sequences, particularly those found in human telomeres. In human malignant cells (HMCs), hnRNP-A1-the most studied hnRNP-is an abundant multifunctional protein that interacts with telomeric DNA and affects telomerase function. In addition, it is believed that other hnRNPs in HMCs may also be involved in the maintenance of telomere length. Accordingly, these proteins are considered possible participants in the processes associated with HMC immortalization. In our review, we discuss the results of studies on different hnRNPs that may be crucial to solving molecular oncological problems and relevant to further investigations of these proteins in HMCs.

Next-generation flexible formats of VNAR domains expand the drug platform's utility and developability.

Therapeutic mAbs have delivered several blockbuster drugs in oncology and autoimmune inflammatory disease. Revenue for mAbs continues to rise, even in the face of competition from a growing portfolio of biosimilars. Despite this success, there are still limitations associated with the use of mAbs as therapeutic molecules. With a molecular mass of 150 kDa, a two-chain structure and complex glycosylation these challenges include a high cost of goods, limited delivery options, and poor solid tumour penetration. There remains an urgency to create alternatives to antibody scaffolds in a bid to circumvent these limitations, while maintaining or improving the therapeutic success of conventional mAb formats. Smaller, less complex binders, with increased domain valency, multi-specific/paratopic targeting, tuneable serum half-life and low inherent immunogenicity are a few of the characteristics being explored by the next generation of biologic molecules. One novel 'antibody-like' binder that has naturally evolved over 450 million years is the variable new antigen receptor (VNAR) identified as a key component of the adaptive immune system of sharks. At only 11 kDa, these single-domain structures are the smallest IgG-like proteins in the animal kingdom and provide an excellent platform for molecular engineering and biologics drug discovery. VNAR attributes include high affinity for target, ease of expression, stability, solubility, multi-specificity, and increased potential for solid tissue penetration. This review article documents the recent drug developmental milestones achieved for therapeutic VNARs and highlights the first reported evidence of the efficacy of these domains in clinically relevant models of disease.

Anti-ICOSL New Antigen Receptor Domains Inhibit T Cell Proliferation and Reduce the Development of Inflammation in the Collagen-Induced Mouse Model of Rheumatoid Arthritis.

Lymphocyte costimulation plays a central role in immunology, inflammation, and immunotherapy. The inducible T cell costimulator (ICOS) is expressed on T cells following peptide: MHC engagement with CD28 costimulation. The interaction of ICOS with its sole ligand, the inducible T cell costimulatory ligand (ICOSL; also known as B7-related protein-1), triggers a number of key activities of T cells including differentiation and cytokine production. Suppression of T cell activation can be achieved by blocking this interaction and has been shown to be an effective means of ameliorating disease in models of autoimmunity. In this study, we isolated specific anti-ICOSL new antigen receptor domains from a synthetic phage display library and demonstrated their ability to block the ICOS/ICOSL interaction and inhibit T cell proliferation. Anti-mouse ICOSL domains, considered here as surrogates for the use of anti-human ICOSL domains in patient therapy, were tested for efficacy in a collagen-induced mouse model of rheumatoid arthritis where they significantly decreased the inflammation of joints and delayed and reduced overall disease progression and severity.