Interleukin 1 receptor antagonist protein. Medical search. Frequent questions

The interleukin-1 receptor antagonist protein (IL-1RN) is a protein that in humans is encoded by the IL1RN gene. (wikipedia.org)
Mutations in the IL1RN gene results in a rare disease called deficiency of the interleukin-1-receptor antagonist (DIRA). (wikipedia.org)
Furthermore, we observed that IL1R1 activation on IL1R1 CD11cWT BMDC preferentially augmented expression of anti-inflammatory mediators tumor necrosis factor alpha induced protein 3 (A20) and interleukin-1 receptor antagonist (IL1Ra/Il1rn), effects that were abrogated by IL1R1 CD11cKO BMDC. (asn-online.org)

IL-1RA is a member of the interleukin 1 cytokine family. (wikipedia.org)
This IL-1α acts as a promoting factor that stimulates the production of IL-1β and of a further cytokine storm from alveolar macrophages. (clinicaltrials.gov)
In vitro, long-term exposure to high glucose and the peptide hormone leptin secreted by adipose tissue induce β-cell apoptosis and production of the proinflammatory cytokine interleukin (IL)-1 in β-cells and pancreatic islets, respectively ( 7 , 8 ). (diabetesjournals.org)
Following AKI, the canonical pro-inflammatory cytokine interleukin-1β (IL1β) is released predominantly from activated myeloid cells and binds to the interleukin-1 receptor R1 (IL1R1). (asn-online.org)
Ample research demonstrates that pathophysiological levels of the pro-inflammatory cytokine interleukin-1 (IL-1) produces detrimental effects on memory functioning. (huji.ac.il)
We previously showed that this cytokine antagonist is upregulated in the serum of obese patients, correlating with BMI and insulin resistance. (diabetesjournals.org)

A recombinant, slightly modified version of interleukin 1 receptor antagonist called anakinra is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. (wikipedia.org)
Anakinra differs from native human IL-1Ra in that it has the addition of a single methionine residue at its amino terminus Interleukin 1 receptor antagonist is used in horses for the treatment of equine lameness secondary to joint and soft-tissue injury. (wikipedia.org)
Anakinra is a recombinant and slightly modified version of the human interleukin 1 receptor antagonist protein. (springwise.com)
Scholars@Duke publication: Feasibility randomised multicentre, double-blind, double-dummy controlled trial of anakinra, an interleukin-1 receptor antagonist versus intramuscular methylprednisolone for acute gout attacks in patients with chronic kidney disease (ASGARD): protocol study. (duke.edu)
This paper describes the protocol for a feasibility randomised controlled trial (RCT) comparing anakinra, a novel interleukin-1 antagonist versus steroids in people with chronic kidney disease (ASGARD). (duke.edu)
METHODS AND ANALYSIS: ASGARD is a two-parallel group double-blind, double-dummy multicentre RCT comparing anakinra 100 mg, an interleukin-1 antagonist, subcutaneous for 5 days against intramuscular methylprednisolone 120 mg. (duke.edu)
Kineret contains the active ingredient anakinra, which is an interleukin-1 (IL-1) receptor antagonist medication. (healthline.com)
Anakinra is the only marketed product that inhibits both IL-1β and IL-1α and hence it is able to block an inflammatory response early on and to prevent the downstream inflammatory cascade. (clinicaltrials.gov)
IL-1 blockade with anakinra induces improvement of the PI/I ratio and markers of systemic inflammation lasting 39 weeks after treatment withdrawal. (diabetesjournals.org)
The drug substance anakinra is a recombinant protein (Interleukin-1 receptor antagonist) produced in E. coli bacteria containing an expression plasmid in which a synthetic gene coding for human IL-1Ra has been inserted.According to the Guideline on the Environmental Risk Assessment of Medicinal Products for Human Use (EMEA 2006), proteins are exempted from environmental risk assessment because they are unlikely to result in significant risk to the environment. (janusinfo.se)
Group 2 will receive aspiration of the knee hemarthrosis as described in group 1 as well as intra-articular administration of 150mg (~5mls) of anakinra (rhIL-1Ra) within 1 to 2 weeks of ACL injury. (researcherprofiles.org)
The drug used in the study, anakinra ( Kineret , Sobi), is a recombinant human interleukin-1 receptor antagonist used in the treatment of rheumatoid arthritis and other less-common inflammatory conditions. (medscape.com)
In addition to a significant improvement in testosterone levels, the men in the study randomized to anakinra also had reductions in C-reactive protein (CRP) and blood pressure, along with improvements in sexual function and grip strength compared with placebo. (medscape.com)
They were randomized 1:1 to self-injected anakinra or placebo twice daily for 4 weeks. (medscape.com)

Spinal and circulating IL-1β levels are significantly elevated in tumor-bearing mice. (nih.gov)
In the light of existing information, one can predict that a possible reason for long life today is the capability of reaching an optimal balance between proinflammatory (C-Reactive Protein, Interleukin 6, Tumor necrosis factor-alpha) and anti-inflammatory (Interleukin-1 receptor antagonist protein, Cortisol, Interleukin-10) molecules. (dergisi.org)
Consistent with M1 polarization, the MWCNTs induced the production and secretion of proinflammatory cytokines tumor necrosis factor-a and interleukin-1β, and proinflammatory LMs leukotriene B4 (LTB4) and prostaglandin E2 (PGE2). (cdc.gov)

Interleukin (IL)-β plays a central role in inflammation and atherosclerosis, but levels of IL-1β, its natural antagonist, IL-1Ra, and their balance in human atherosclerotic lesions, are unknown. (go.jp)
BACKGROUND: To investigate potential cardiovascular and other effects of long-term pharmacological interleukin 1 (IL-1) inhibition, we studied genetic variants that produce inhibition of IL-1, a master regulator of inflammation. (ox.ac.uk)
This protein is primarily found in the skin where it helps regulate inflammation, part of the body's early immune response. (medlineplus.gov)
Inflammation in the skin is stimulated when other proteins called IL-36 alpha (α), IL-36 beta (β), or IL-36 gamma (γ) attach to (bind) a specific receptor protein. (medlineplus.gov)
Interleukin-1 gene cluster polymorphisms are associated with nutritional status and inflammation in patients with end-stage renal disease. (dadamo.com)
Interleukin-1beta (IL-1beta) and its receptor antagonist (IL-1Ra) may play a pivotal role in the pathogenesis of wasting and inflammation. (dadamo.com)
METHODS: To investigate effects of the IL-1 gene cluster polymorphisms on wasting and inflammation, we studied 189 ESRD patients (52+/- 12 years, 62% males) close to the start of renal replacement therapy. (dadamo.com)
We used serum high-sensitivity C-reactive protein (hsCRP) as a marker of inflammation. (dadamo.com)
CONCLUSION: The investigated IL-1 gene cluster polymorphisms were associated with nutritional status and inflammation in ESRD patients, but marked differences were found between the genders. (dadamo.com)
METHODS: To analyze the impact of cocaine and cannabis use on levels of markers of monocyte activation (sCD163 and sCD14) and systemic inflammation (interleukin-6 [IL-6]) in AUD patients admitted for hospital treatment between 2013 and 2018. (bvsalud.org)
We believe that's clinically relevant against the background of the large CANTOS trial published recently showing that antagonism of the inflammation of interleukin-1 reduces cardiovascular mortality," he noted. (medscape.com)

Shanthi was the first to receive therapies that had not previously been used in elephants, including intra-articular (joint) injections of Interleukin-1 Receptor Antagonist Protein (IRAP)-a treatment using autologous conditioned serum to slow the progression of osteoarthritis-from 2016 through 2018 , and Osphos-an intra-muscular medication that helps to minimize bony remodeling-in April 2019 . (si.edu)
He touched on the use of hyaluronic acid combined with steroid in intra-articular joint injections and the use of Interleukin-1 Receptor Antagonist Protein (IRAP), Platelet-Rich Plasma (PRP), stem cells and shockwave therapy for joint, tendon and ligament injuries. (selectbreeders.com)

High serum levels of lipopolysaccharides (LPS), soluble CD14 (sCD14), and LPS-binding protein (LBP) combined with low endotoxin core antibody (EndoCAb) titres suggested systemic MT in CWD patients developing IRIS. (bvsalud.org)

Kineret is also used to treat deficiency of interleukin-1 receptor antagonist (DIRA). (healthline.com)
Typical examples of monogenic forms of osteomyelitis represent Majeed syndrome or DIRA (Deficiency of Interleukin-1 Receptor Antagonist), with an altered IL-1 signalling pathway. (biomedcentral.com)
Liver disease progression in patients with alpha-1 antitrypsin deficiency and protease inhibitor ZZ genotype with or without lung disease. (cdc.gov)
Alpha-1 antitrypsin (AAT) augmentation and the liver phenotype of adults with AAT deficiency (genotype Pi*ZZ). (cdc.gov)

Kineret works to treat DIRA by blocking a protein that's found in many different tissues and organs in the body. (healthline.com)

both alleles increase soluble IL-1Ra protein concentration. (ox.ac.uk)
Adipose tissue contributes to the production of TNF-alpha, which is reflected by elevated levels of soluble TNF-alpha receptors, IL-6, IL-1 receptor antagonist, and C-reactive protein. (regionh.dk)

Its role in counteracting the proinflammatory effects of IL-1 is being studied by numerous research groups. (creativebiomart.net)

In these patients, IL-9 impairs interferon gamma production and synergistically promotes interleukin-4-induced IgE secretion. (cusabio.cn)

It binds to IL-1 receptors in competition with IL-1, but does not elicit intracellular response from this binding. (creativebiomart.net)
This receptor is composed of two related, but non-identical, subunits that transmit intracellular signals via a pathway that is mostly shared with certain other receptors. (dadamo.com)
Three forms of IL-1Ra have been described, two of which are expressed as intracellular proteins (icIL-1RaI and icIL-1RaII) and one of which is secreted (sIL-1Ra) ( 2 ). (diabetesjournals.org)
Increased production of intracellular interleukin-1 receptor antagonist type I in the synovium of mice with collagen-induced arthritis: a possible role in the resolution of arthritis. (ox.ac.uk)

IL-1RN was initially called the IL-1 inhibitor and was discovered separately in 1984 by two independent laboratories. (wikipedia.org)
Interleukin-1 receptor antagonist (IL-1Ra) is a naturally occurring inhibitor of IL-1. (researcherprofiles.org)
Thus, the investigators hypothesize that early injection of IL-1 inhibitor (IL-1Ra) into the knee joint of patients suffering recent ACL injury will decrease the incidence of cartilage damage later in life. (researcherprofiles.org)
The cell-free media from MWCNT-polarized macrophages induced the migration of neutrophilic cells (differentiated from HL-60), which was blocked by Acebilustat, a specific leukotriene A4 hydrolase inhibitor, or LY239111, an LTB4 receptor antagonist, but not NS-398, a cyclooxygenase 2 inhibitor, revealing LTB4 as a major mediator of neutrophil chemotaxis from MWCNT-polarized macrophages. (cdc.gov)

The interleukin-1 receptor antagonist (IL-1Ra) is a member of the interleukin (IL)-1 family that binds to IL-1 receptors without inducing a cellular response, thereby antagonizing the effects of IL-1α and -1β ( 1 ). (diabetesjournals.org)

This protein inhibits the activities of interleukin 1, alpha (IL1A) and interleukin 1, beta (IL1B), and modulates a variety of interleukin 1 related immune and inflammatory responses. (wikipedia.org)

IL-1β was measured by quantifying gene expression via quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). (nih.gov)
Recombinant Human Interleukin-1 Receptor Antagonist Protein is produced by our E.coli expression system and the target gene encoding Arg26-Glu177 is expressed. (creativebiomart.net)
The IL36RN gene provides instructions for making a protein called interleukin 36 receptor antagonist (IL-36Ra). (medlineplus.gov)
The IL36RN gene mutations associated with GPP reduce the amount of IL-36Ra protein in the skin or eliminate it altogether. (medlineplus.gov)
To substantiate the physiological role of IL-1 in learning and memory we examined the induction of IL-1 gene expression following a learning experience, and the effects of IL-1 signaling blockade, by either genetic or pharmacological manipulations, on memory functioning. (huji.ac.il)
We show that IL-1 gene expression is induced in the hippocampus 24 h following fear-conditioning in wild type mice, but not in two mouse strains with impaired IL-1 signaling. (huji.ac.il)
Angiotensin-converting enzyme 1 gene polymorphisms in patients with systemic sclerosis-associated interstitial lung disease: a single centre retrospective observational study. (cdc.gov)
Transforming Growth Factor ß1 and Gap Junction Protein Alpha 4 Gene Heterogeneity in Relation to the Severity of Clinical Disease in Cystic Fibrosis. (cdc.gov)

Both clusters 1 and 4 have largely normal glycemia, adequate insulin secretion, and adequate or good insulin sensitivity. (todaysdietitian.com)
Interleukin (IL)-1 impairs insulin secretion and induces β-cell apoptosis. (diabetesjournals.org)

The use of amino acids, proteins and peptides is not considered to have any environmental impact. (janusinfo.se)
According to the European Medicines Agency guideline on environmental risk assessments for pharmaceuticals (EMA/CHMP/SWP/4447/00),vitamins, electrolytes, amino acids, peptides, proteins, carbohydrates, lipids proteins, vaccines and herbal medicinal products are exempted because they are unlikely to result in significant risk to the environment. (janusinfo.se)
This is a Phase 1/2 study to assess the safety and efficacy of ELI-002 7P immunotherapy (a lipid-conjugated immune-stimulatory oligonucleotide [Amph-CpG-7909] plus a mixture of lipid-conjugated peptide-based antigens [Amph-Peptides 7P]) as adjuvant treatment in subjects with solid tumors with mutated KRAS/NRAS. (ucbraid.org)

Knowledge of protein levels in atherosclerosis and the influence of a functional IL-1Ra polymorphism would increase the understanding of atherosclerosis pathogenesis. (go.jp)
In line with this, the presence of an IL-1Ra intron 2 polymorphism known to increase IL-1Ra levels, and possibly the IL-1Ra:IL-1β ratio, was associated with reduced coronary atherosclerosis. (go.jp)

A method to induce Interleukin-1 Receptor Antagonist Protein from autologous whole blood. (ouhsc.edu)

Blocking IL-1 signaling either by intrathecal administration of interleukin-1 receptor antagonist (IL-1ra) or by genetic deletion (interleukin-1 receptor knockout [Il1r1-/-]) does not alleviate HNCP. (nih.gov)
As IL1R1 is known to signal through the pro-inflammatory Toll-like receptor (TLR)/MyD88 pathway, we initially hypothesized that myeloid cell IL1R1 activation would exacerbate AKI. (asn-online.org)

we analysed its effect on fever, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, numbers of swollen and tender joints, the assessment of disease activity (by physician and parent/patient) and pain (by parent/patient), and American College of Rheumatology (ACR) pediatric core set criteria for JIA activity. (bmj.com)
METHODS: Arthritis was induced in DBA/1 mice by immunization with type II collagen, and the production of IL-1Ra isoforms was examined in whole joints and in dissected synovial tissues by reverse transcription-polymerase chain reaction (RT-PCR), RNase protection assay, Western blotting, immunostaining, and in situ hybridization. (ox.ac.uk)
Western blot studies showed that icIL-1Ra1 protein levels increased in the joints during the course of CIA and that icIL-1Ra3 protein was also present in low amounts. (ox.ac.uk)

Measured by the dose-dependent inhibition of IL-1 stimulation of D10S cells. (creativebiomart.net)
INTERPRETATION: Human genetic data suggest that long-term dual IL-1α/β inhibition could increase cardiovascular risk and, conversely, reduce the risk of development of rheumatoid arthritis. (ox.ac.uk)

A recent publication has shown that this is due to the early release of interleukin-1α (IL-1α) from lung epithelial cells that are infected by the virus. (clinicaltrials.gov)

Interleukin 1 Genetics Consortium None. (ox.ac.uk)

IL-1 receptor antagonist in metabolic diseases: Dr Jekyll or Mr Hyde? (wikipedia.org)
Explore our series of high-quality proteins covering comprehensive diagnostic indicators in order to facilitate the in vitro diagnostic research of neurological diseases. (acrobiosystems.com)
Pre-formed fibrils are an invaluable preclinical model for exploring pathogenesis of neurological diseases through aggregation of misfolded proteins. (acrobiosystems.com)

In the present study, we used data from two other cohort studies in which we have measured multiple proteins by the proximity extension assay (PEA) [ 13 ] to test the hypothesis that proteins being linked to all five MetS components would also be associated with incident MetS and possibly causally involved in the development of MetS. (biomedcentral.com)
This cohort has since then been reinvestigated multiple times and the present study used data from the reinvestigation at age 77 years (in 1997-2001) when the same proteins as evaluated in PIVUS were measured (n = 785). (biomedcentral.com)
Cohort 1 will enroll participants with locally advanced or metastatic hepatocellular carcinoma (HCC) who have not received prior systemic therapy for their disease. (ucbraid.org)

The aim of this study was to assess the correlation between polymorphisms in the genes coding for mannose-binding lectin (MBL) and interleukin-1 receptor antagonist (IL1-Ra) and RVCC in women from São Paulo, Brazil. (usp.br)

Resveratrol prevents dexamethasone-induced expression of the muscle atrophy-related ubiquitin pgases atrogin-1 and MuRF1 in cultured myotubes through a SIRT1-dependent mechanism. (per-olofhasselgren.com)

O presente estudo teve como objetivo avaliar as associações entre os polimorfismos nos genes que codificam a lecitina ligadora de manose (MBL) e do antagonista do receptor da interleucina 1 (IL1-Ra) com a candidíase vulvovaginal recorrente (CVVR) em mulheres brasileiras. (usp.br)

Unlike inflammatory or nerve-injured pain, HNCP is independent of IL-1 signaling. (nih.gov)
Endotoxin stimulation increased IL-1β levels more than IL-1Ra levels (ie, promoted a pro-inflammatory state). (go.jp)
Activation of innate immunity changed the balance between IL-1β and IL-1Ra in atherosclerotic arteries towards a more pro-inflammatory state. (go.jp)
Increased levels of several inflammatory and cardiovascular disease-related plasma proteins have been associated with impaired lung function. (lu.se)
To control inflammatory reactions, the IL-36Ra protein binds to the receptor protein so that IL-36α, IL-36β, and IL-36γ cannot. (medlineplus.gov)
The secreted form of the interleukin-1 receptor antagonist (IL-1Ra) is an acute-phase protein intervening in the counterregulation of inflammatory processes. (diabetesjournals.org)

Biologic Therapy for Joint Disease Platelet-Rich Plasma, Interleukin-1 Receptor Antagonist. (ttu.edu)
The aim was to study the association between plasma proteomics and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio. (lu.se)
Results Plasma fatty acid-binding protein 4, interleukin-1 receptor antagonist, interleukin-6 and leptin were negatively associated with FEV1 and paraoxonase 3 was positively associated therewith. (lu.se)
[ 1 ] Urine osmolality is greater than plasma osmolality. (medscape.com)

There are a few molecules of the IL-1 family. (dadamo.com)
Neural factors are a class of protein molecules with neurotrophic activity that can promote the survival and regeneration of nerve cells. (acrobiosystems.com)

Fresh and endotoxin-stimulated explanted human atherosclerotic and normal arteries were analyzed for IL-1β, IL-1Ra and IL-1 receptor 1 (IL-1R1) using TaqMan PCR and enzyme-linked immunosorbent assay. (go.jp)
Interleukin-1 (IL-1) levels in the human knee joint increase transiently after an ACL injury. (researcherprofiles.org)
The "self"-protein albumin in mouse airway fluid was uniquely modified by GSH-MDI at position 414K, a preferred site of MDI reactivity on human albumin. (cdc.gov)

To evaluate the efficacy and safety of interleukin-1 receptor antagonist (IL-1Ra) in patients with rheumatoid arthritis (RA). (nih.gov)
It is used in the treatment of rheumatoid arthritis, an autoimmune disease in which IL-1 plays a key role. (dadamo.com)

Their cardiovascular risk wasn't elevated, but their overall mortality was 40% higher than cluster 1, which is the most prevalent group. (todaysdietitian.com)
Offspring Study (total n=2874), to cross-sectionally study 242 cardiovascular disease-and metabolism-linked proteins in relation to FEV1, FVC (both % predicted) and FEV1/FVC ratio. (lu.se)

Cardiometabolic effects of genetic upregulation of the interleukin 1 receptor antagonist: a Mendelian randomisation analysis. (ox.ac.uk)

IL-1 inhibits the function and induces apoptosis of β-cells ( 9 ) and has been implicated as a mediator of the β-cell destruction leading to type 1 diabetes ( 10 ). (diabetesjournals.org)

The efficacy of a therapeutic antibody depends on the Fab fragment and its binding activity to the target antigen, but also depends on the Fc fragment and its interaction with key Fc receptors.Therefore, candidates must be tested against a panel of receptors during antibody engineering. (acrobiosystems.com)

Treatment of murine macrophages (J774A.1) with Mitsui-7 MWCNTs increased the expression of Alox5 mRNA and protein in a concentration- and time-dependent manner. (cdc.gov)

In this study, we explore the structure-function relationships among therapeutic proteins. (crimsonpublishers.com)
We collected sequence data of the therapeutic proteins from Drug Bank and KEGG databases, then grouped different mechanistic and therapeutic classes. (crimsonpublishers.com)
Eight classes could be made for the various functionalities, and a corresponding correlation between each class and the relevant structure of the therapeutic protein category using RMSD scores was built. (crimsonpublishers.com)

The purpose of this study is to develop a novel syngeneic model of HNCP in immunocompetent mice to examine the contribution of IL-1 signaling. (nih.gov)
Moreover, we report that mice with transgenic over-expression of IL-1 receptor antagonist restricted to the CNS (IL-1raTG) display impaired hippocampal-dependent and intact hippocampal-independent memory in the water maze and fear-conditioning paradigms. (huji.ac.il)
We further demonstrate that continuous administration of IL-1ra via osmotic minipumps during prenatal development disrupt memory performance in adult mice, suggesting that IL-1 plays a critical role not only in the formation of hippocampal-dependent memory but also in normal hippocampal development. (huji.ac.il)

Patients were randomized to 1 of 4 treatment groups: placebo or a single, self-administered subcutaneous injection of IL-1Ra at a daily dose of 30 mg, 75 mg, or 150 mg. (nih.gov)
During the treatment with the moisturizing cream, significantly higher conductance values and lower TEWL values were found on the moisturizer-treated side, accompanied by a decreasing IL-1ra/IL-1α ratio and immature CEs. (karger.com)
Eligible participants will initially be randomly assigned to one of several treatment arms (Stage 1). (ucbraid.org)
Participants who experience loss of clinical benefit or unacceptable toxicity during Stage 1 may be eligible to receive treatment with a different treatment combination (Stage 2). (ucbraid.org)
The panel makes a conditional recommendation for interleukin (IL)-6 receptor antagonist monoclonal antibody treatment and high-flow nasal oxygen or continuous positive airway pressure in patients with hypoxaemic respiratory failure. (bvsalud.org)

These include the Toll family of innate immune receptors and the receptor for IL-18. (dadamo.com)

Levels of IL-1β, IL-1Ra and IL-1R1 mRNA were significantly increased in atherosclerotic arteries compared with normal arteries. (go.jp)

However, in ACL injuries the balance of these two proteins is disturbed transiently after injury, with the effects of IL-1 dominating this balance. (researcherprofiles.org)

IL-1 is one of the most important immune modifying interleukins. (dadamo.com)

We used a targeted proteomics assay to identify associations of circulating proteins with MetS and its components, cross-sectionally and longitudinally. (biomedcentral.com)

Organisms2

Chemicals and Drugs20

Phenomena and Processes1

IL1RN3

Cytokine6

Anakinra14

Tumor3

Inflammation11

Intra-Articular2

Serum1

Deficiency4

DIRA1

Soluble2

Proinflammatory1

Interferon1

Intracellular4

Inhibitor4

Binds to IL-1 receptors1

IL1B1

Gene8

Secretion2

Peptides3

Polymorphism2

Autologous1

Il1r12

Joints3

Inhibition2

Epithelial cells1

Genetics1

Diseases3

Cohort3

Polymorphisms1

Ubiquitin1

Genes1

Inflammatory6

Plasma4

Molecules2

Human3

Rheumatoid2

Cardiovascular2

Genetic1

Inhibits1

Antigen1

Macrophages1

Therapeutic3

Mice3

Treatment5

Innate1

MRNA1

Effects1

Immune1

Cross-sectionally1