Significant and variable linear polarization during the prompt optical flash of GRB 160625B.

Newly formed black holes of stellar mass launch collimated outflows (jets) of ionized matter that approach the speed of light. These outflows power prompt, brief and intense flashes of γ-rays known as γ-ray bursts (GRBs), followed by longer-lived afterglow radiation that is detected across the electromagnetic spectrum. Measuring the polarization of the observed GRB radiation provides a direct probe of the magnetic fields in the collimated jets. Rapid-response polarimetric observations of newly discovered bursts have probed the initial afterglow phase, and show that, minutes after the prompt emission has ended, the degree of linear polarization can be as high as 30 per cent-consistent with the idea that a stable, globally ordered magnetic field permeates the jet at large distances from the central source. By contrast, optical and γ-ray observations during the prompt phase have led to discordant and often controversial results, and no definitive conclusions have been reached regarding the origin of the prompt radiation or the configuration of the magnetic field. Here we report the detection of substantial (8.3 ± 0.8 per cent from our most conservative simulation), variable linear polarization of a prompt optical flash that accompanied the extremely energetic and long-lived prompt γ-ray emission from GRB 160625B. Our measurements probe the structure of the magnetic field at an early stage of the jet, closer to its central black hole, and show that the prompt phase is produced via fast-cooling synchrotron radiation in a large-scale magnetic field that is advected from the black hole and distorted by dissipation processes within the jet.

Constraints on Lorentz Invariance Violation from HAWC Observations of Gamma Rays above 100 TeV.

Because of the high energies and long distances to the sources, astrophysical observations provide a unique opportunity to test possible signatures of Lorentz invariance violation (LIV). Superluminal LIV enables the decay of photons at high energy. The high altitude water Cherenkov (HAWC) observatory is among the most sensitive gamma-ray instruments currently operating above 10 TeV. HAWC finds evidence of 100 TeV photon emission from at least four astrophysical sources. These observations exclude, for the strongest of the limits set, the LIV energy scale to 2.2×10^{31} eV, over 1800 times the Planck energy and an improvement of 1 to 2 orders of magnitude over previous limits.

Multiple Galactic Sources with Emission Above 56 TeV Detected by HAWC.

We present the first catalog of gamma-ray sources emitting above 56 and 100 TeV with data from the High Altitude Water Cherenkov Observatory, a wide field-of-view observatory capable of detecting gamma rays up to a few hundred TeV. Nine sources are observed above 56 TeV, all of which are likely galactic in origin. Three sources continue emitting past 100 TeV, making this the highest-energy gamma-ray source catalog to date. We report the integral flux of each of these objects. We also report spectra for three highest-energy sources and discuss the possibility that they are PeVatrons.

Cortical abnormalities in bipolar disorder: an MRI analysis of 6503 individuals from the ENIGMA Bipolar Disorder Working Group.

Despite decades of research, the pathophysiology of bipolar disorder (BD) is still not well understood. Structural brain differences have been associated with BD, but results from neuroimaging studies have been inconsistent. To address this, we performed the largest study to date of cortical gray matter thickness and surface area measures from brain magnetic resonance imaging scans of 6503 individuals including 1837 unrelated adults with BD and 2582 unrelated healthy controls for group differences while also examining the effects of commonly prescribed medications, age of illness onset, history of psychosis, mood state, age and sex differences on cortical regions. In BD, cortical gray matter was thinner in frontal, temporal and parietal regions of both brain hemispheres. BD had the strongest effects on left pars opercularis (Cohen's d=-0.293; P=1.71 × 10-21), left fusiform gyrus (d=-0.288; P=8.25 × 10-21) and left rostral middle frontal cortex (d=-0.276; P=2.99 × 10-19). Longer duration of illness (after accounting for age at the time of scanning) was associated with reduced cortical thickness in frontal, medial parietal and occipital regions. We found that several commonly prescribed medications, including lithium, antiepileptic and antipsychotic treatment showed significant associations with cortical thickness and surface area, even after accounting for patients who received multiple medications. We found evidence of reduced cortical surface area associated with a history of psychosis but no associations with mood state at the time of scanning. Our analysis revealed previously undetected associations and provides an extensive analysis of potential confounding variables in neuroimaging studies of BD.

Preservation of fruit and vegetable discards with sodium metabisulfite.

Two series of experiments were performed to investigate the aerobic preservation of fruit and vegetable discards (FVD) using sodium metabisulfite (SMB). In Exp. 1, metabisulfite was applied at 0, 2, 4, 6, and 8 g/kg FVD for 0, 3, 6, 9, and 12 d. Metabisulfite treatment at 6 and 8 g/kg FVD was highly effective in controlling putrefaction and preserving the nutrient components for 6 and 9 d, respectively. In the pilot-scale experiment (Exp. 2), SMB was applied at 0 and 8 g/kg FVD in a 600-L bucket for 0, 6, and 9 d in an outdoor environment. The SMB treatment was highly effective in maintaining the integrity and freshness of FVD, suppressing microbial proliferation, and preserving the nutrient constituents. Under the conditions of this study, SMB effectively preserved FVD in an aerobic environment, enabling their more efficient long-term recycling through livestock feed or development of value-added products.

Effective acute care handover to GP: optimising the structure to improve discharge documentation.

Time and resource constraints have often led to the use of assessment records as discharge communications from acute and emergency departments. However, whether this addresses the primary care needs has not been demonstrated. This study examined the optimal structure that can impart key discharge information effectively using feedback from general practitioners (GP). We implemented an electronic assessment template that focused on the most relevant headings. Prespecified process measures were examined and qualitative thematic analysis of free-text comments from GP surveys were conducted to optimise the document. Our findings suggest that the structure of a discharge summary can influence the quality of information, users' compliance and readers' perceptions of the length of the letter.

Self-consolidation mechanism of nanostructured Ti5Si3 compact induced by electrical discharge.

Electrical discharge using a capacitance of 450 µF at 7.0 and 8.0 kJ input energies was applied to mechanical alloyed Ti5Si3 powder without applying any external pressure. A solid bulk of nanostructured Ti5Si3 with no compositional deviation was obtained in times as short as 159 µsec by the discharge. During an electrical discharge, the heat generated is the required parameter possibly to melt the Ti5Si3 particles and the pinch force can pressurize the melted powder without allowing the formation of pores. Followed rapid cooling preserved the nanostructure of consolidated Ti5Si3 compact. Three stepped processes during an electrical discharge for the formation of nanostructured Ti5Si3 compact are proposed: (a) a physical breakdown of the surface oxide of Ti5Si3 powder particles, (b) melting and condensation of Ti5Si3 powder by the heat and pinch pressure, respectively, and (c) rapid cooling for the preservation of nanostructure. Complete conversion yielding a single phase Ti5Si3 is primarily dominated by the solid-liquid mechanism.

Calcium and vitamin D intake maintained from preovariectomy independently affect calcium metabolism and bone properties in Sprague Dawley rats.

UNLABELLED: The interaction of habitual Ca and vitamin D intake from preovariectomy to 4 months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake suppressed net bone turnover, and both nutrients independently benefitted trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D status is most beneficial. INTRODUCTION: Dietary strategies to benefit bone are typically tested prior to or after menopause but not through menopause transition. We investigated the interaction of Ca and vitamin D status on Ca absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned through estrogen deficiency. METHODS: Sprague Dawley rats were randomized at 8 weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 µg) vitamin D/kg diet (2 × 3 factorial design) and ovariectomized at 12 weeks. Urinary (45)Ca excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks. Femoral and tibiae structure (by µCT), dynamic histomorphometry, and bone Ca content were assessed. RESULTS: Mean 25(OH)D for rats on the 50, 100, 1,000 IU vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake ameliorated net bone turnover, reduced fractional Ca absorption and bone resorption, and increased net Ca absorption. Tibial and femoral trabecular structures were enhanced independently by higher Ca and vitamin D intake. Tibial bone width and fracture resistance were enhanced by higher vitamin D intake. Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca × vitamin D interaction existed in femur length, tibial Ca content, and mass of the soft tissue/extracellular fluid compartment. CONCLUSIONS: Adequate Ca intake and serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health, mostly through independent effects of Ca and vitamin D.

An important role of tumor necrosis factor receptor-2 on natural killer T cells on the development of dsRNA-enhanced Th2 cell response to inhaled allergens.

BACKGROUND: Recent evidence indicates that TNF-α is a key mediator of the development of dsRNA-enhanced Th2 cell response to inhaled allergens. Natural killer T (NKT) cells may be a candidate source of Th2-polarizing cytokines. OBJECTIVE: The objective of this study was to evaluate the role of lung NKT cells on the development of TNF-α-mediated Th2 cell response. METHODS: A virus-associated asthma mouse model was generated by the administration of ovalbumin (OVA, 75 µg) and poly[I:C] (0.1 µg). Role of NKT and type I NKT cells was evaluated using CD1d- and Jα18-deficient mice. TNF-α receptors (TNFRs) were antagonized by using TNFR blocking peptides. RESULTS: The number of infiltrated NKT cells was increased in a virus-associated asthma mouse model. Increase in Th2 and Th17 cytokine levels in wild-type mice were abolished in both CD1d- and Jα18-deficient mice. In vitro co-culture experiments with alveolar macrophages and NKT cells showed that TNF-α produced by macrophages in the presence of poly[I:C] acts on NKT cells, inducing production of Th2-polarizing cytokines. Moreover, the induction of Th2-polarizing cytokines by poly[I:C] or recombinant TNF-α was impaired in both CD1d- and Jα18-deficient mice and that the above effect was reversed by a TNF-α receptor-2 (TNFR2) blocking peptide, but not by a TNFR1 blocker. CONCLUSIONS: These findings suggest that NKT cells play a key role in the development of Th2 cell response to inhaled allergens and that TNF-α produced by alveolar macrophages induces Th2 cell response, via TNFR2 on NKT cells.

Extracellular vesicles, especially derived from Gram-negative bacteria, in indoor dust induce neutrophilic pulmonary inflammation associated with both Th1 and Th17 cell responses.

BACKGROUND: Many bacterial components in indoor dust can evoke inflammatory pulmonary diseases. Bacteria secrete nanometre-sized vesicles into the extracellular milieu, but it remains to be determined whether bacteria-derived extracellular vesicles in indoor dust are pathophysiologically related to inflammatory pulmonary diseases. OBJECTIVE: To evaluate whether extracellular vesicles (EV) in indoor air are related to the pathogenesis of pulmonary inflammation and/or asthma. METHODS: Indoor dust was collected from a bed mattress in an apartment. EV were prepared by sequential ultrafiltration and ultracentrifugation. Innate and adaptive immune responses were evaluated after airway exposure of EV. RESULTS: Repeated intranasal application of indoor-dust-induced neutrophilic pulmonary inflammation accompanied by lung infiltration of both Th1 and Th17 cells. EV 50-200 nm in diameter were present (102.5 µg protein concentration/g dust) in indoor dust. These vesicles were internalized by airway epithelial cells and alveolar macrophages, and this process was blocked by treatment of polymyxin B (an antagonist of lipopolysaccharide, an outer-membrane component of Gram-negative bacteria). Intranasal application of 0.1 or 1 µg of these vesicles for 4 weeks elicited neutrophilic pulmonary inflammation. This phenotype was accompanied by lung infiltration of both Th1 and Th17 cells, which were reversed by treatment of polymyxin B. Serum dust EV-reactive IgG1 levels were significantly higher in atopic children with asthma than in atopic healthy children and those with rhinitis or dermatitis. CONCLUSION & CLINICAL RELEVANCE: Indoor dust EV, especially derived from Gram-negative bacteria, is a possible causative agent of neutrophilic airway diseases.

Isolation of the human PEX12 gene, mutated in group 3 of the peroxisome biogenesis disorders.

The peroxisome biogenesis disorders (PBDs) are a group of genetically heterogeneous diseases lethal in early infancy. Although the clinical features of PBD patients may vary, cells from all PBD patients exhibit a defect in the import of one or more classes of peroxisomal matrix proteins. This cellular phenotype is shared by yeast pex mutants, and human orthologues of yeast PEX genes have been shown to be defective in some groups of PBD patients. We identified a putative human orthologue of ScPEX12 by screening the database of expressed sequence tags for cDNAs capable of encoding a protein similar to yeast Pex12p. Although its sequence similarity to yeast Pex12 proteins was limited, PEX12 shared the same subcellular distribution as yeast Pex12p and localized to the peroxisome membrane. PEX12 expression restored peroxisomal protein import in fibroblasts from PBD patients of complement group 3 (CG3) and frameshift mutations in PEX12 were detected in two unrelated CG3 patients. These data demonstrate that mutations in PEX12 are responsible for CG3 of the PBD and that PEX12 plays an essential role in peroxisomal matrix protein import.

The Impact of Frailty Status on Pulmonary Function and Mortality in Older Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective observational cohort. SETTING AND PARTICIPANTS: At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center. MEASUREMENTS: Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function. RESULTS: Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors. CONCLUSION: Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.

Synthetic peptides containing ITIM-like sequences of IREM-1 (CD300F) differentially regulate MyD88 and TRIF-mediated TLR signalling through activation of SHP and/or PI3K.

The immune receptor expressed on myeloid cells 1 (IREM-1/CD300F) has been shown to inhibit various inflammatory processes in myeloid cells, such as macrophages and mast cells. IREM-1 exerts its inhibitory effect through its intracellular immunoreceptor tyrosine-based inhibition motifs (ITIMs). In order to generate immunomodulatory molecules that can regulate the inflammatory activation of macrophages, decapeptides representing each of the five ITIM-like sequences in the cytoplasmic tail of IREM-1 were synthesized in conjugation with human immunodeficiency virus-transactivator of transcription (HIV-TAT(48-57)), which was added to promote internalization of the peptides. Interestingly, all these TAT-ITIM fusion peptides inhibited Toll-like receptor (TLR)-mediated production of proinflammatory molecules, including matrix metalloproteinase (MMP)-9, tumour necrosis factor (TNF)-α, monocyte chemotactic protein-1 (MCP-1) and interleukin (IL)-8. When various TLR ligands were used to stimulate the human macrophage-like cell line human acute monocytic leukaemia cell line (THP)-1, the TAT-ITIM peptides blocked both myeloid differentiation factor 88 (MyD88) and Toll-interleukin 1 receptor (TIR)-domain-containing adapter-inducing interferon-ß (TRIF)-mediated TLR signalling pathways. Utilization of specific inhibitors and detection of the active form of signalling adaptors by Western blot analysis further demonstrated that the inhibitory effects of these TAT-ITIM peptides require activation of Src homology 2 (SH2)-containing tyrosine phosphatase (SHP) and/or phosphoinositide 3-kinase (PI3K). These data indicate that these synthetic peptides may be used to regulate immune responses that involve TLR-mediated inflammatory activation of macrophages.

Staphylococcus aureus-derived extracellular vesicles induce neutrophilic pulmonary inflammation via both Th1 and Th17 cell responses.

BACKGROUND: Recent evidence indicates that Staphylococcus aureus, one of the most important human pathogens, secretes vesicles into the extracellular milieu. OBJECTIVE: To evaluate whether inhalation of S. aureus-derived extracellular vesicles (EV) is causally related to the pathogenesis of inflammatory pulmonary diseases. METHODS: Staphylococcus aureus EV were prepared by sequential ultrafiltration and ultracentrifugation. The innate immune response was evaluated in vitro after the application of EV to airway epithelial cells and alveolar macrophages. In vivo innate and adaptive immune responses were evaluated after airway exposure to EV. Adjuvant effects of EV on the development of hypersensitivity to inhaled allergens were also evaluated after airway sensitization with S. aureus EV and ovalbumin (OVA). RESULTS: Staphylococcus aureus and S. aureus EV were detected in house dust. Alveolar macrophages produced both tumor necrosis α (TNF-α) and interleukin 6 (IL-6) after in vitro stimulation with S. aureus EV, whereas airway epithelial cells produced only IL-6. Repeated airway exposure to S. aureus EV induced both Th1 and Th17 cell responses and neutrophilic pulmonary inflammation, mainly via a Toll-like receptor 2 (TLR2)-dependent mechanism. In terms of adjuvant effects, airway sensitization with S. aureus EV and OVA resulted in neutrophilic pulmonary inflammation after OVA challenge alone. This phenotype was partly reversed by the absence of interferon γ (IFN-γ) or IL-17. CONCLUSION: Staphylococcus aureus EV can induce Th1 and Th17 neutrophilic pulmonary inflammation, mainly in a TLR2-dependent manner. Additionally, S. aureus EV enhance the development of airway hypersensitivity to inhaled allergens.

Fine-mapping the immunodominant antibody epitopes on consensus sequence-based HIV-1 envelope trimer vaccine candidates.

The HIV-1 envelope glycoprotein (Env) trimer is the key target for vaccines aimed at inducing neutralizing antibodies (NAbs) against HIV-1. The clinical candidate immunogen ConM SOSIP.v7 is a stabilized native-like HIV-1 Env trimer based on an artificial consensus sequence of all HIV-1 isolates in group M. In preclinical studies ConM SOSIP.v7 trimers induced strong autologous NAb responses in non-human primates (NHPs). To fine-map these responses, we isolated monoclonal antibodies (mAbs) from six cynomolgus macaques that were immunized three times with ConM SOSIP.v7 protein and boosted twice with the closely related ConSOSL.UFO.664 immunogen. A total of 40 ConM and/or ConS-specific mAbs were isolated, of which 18 were retrieved after the three ConM SOSIP.v7 immunizations and 22 after the two immunizations with ConSOSL.UFO.664. 22 mAbs (55%) neutralized the ConM and/or ConS virus. Cross-neutralization of ConS virus by approximately one-third of the mAbs was seen prior to ConSOSL.UFO.664 immunization, albeit with modest potency. Neutralizing antibodies predominantly targeted the V1 and V2 regions of the immunogens, with an apparent extension towards the V3 region. Thus, the V1V2V3 region is immunodominant in the potent NAb response elicited by two consensus sequence native-like HIV-1 Env immunogens. Immunization with these soluble consensus Env proteins also elicited non-neutralizing mAbs targeting the trimer base. These results inform the use and improvement of consensus-based trimer immunogens in combinatorial vaccine strategies.

Simple isotopic method using oral stable or radioactive tracers for estimating fractional calcium absorption in adult women.

UNLABELLED: We extended a simple oral method for estimating fractional calcium absorption determined by double isotopic methods using radioactive or stable isotope across wide age of adult women. Fractional calcium absorption can be estimated by using either a radioactive or stable oral isotope across the entire age spectrum of adult women. INTRODUCTION: A method for estimating fractional calcium absorption using a single serum collection following a single oral radioactive isotopic tracer has been validated against a classical double isotopic tracer ratio method in adults. Our goal was to extend this simplified method to include use of stable isotopes and a broad age range. METHODS: We used our database of 56 observations from 26 white adult women aged 19-67 years receiving either radioactive or stable isotopes. Reference values for fractional calcium absorption were determined from 24-h double isotopic ratios in serum and urine and from full kinetic modeling. RESULTS: Equations for estimating fractional calcium absorption were developed from isotopic enrichment in serum and urine from an oral tracer and measures of body size using the multiple linear regression analysis. Equations using a 4- to 6-h sample following an oral dose of either a stable or radioactive isotope corrected for body size were highly correlated with the reference values for fractional calcium absorption across different aged populations (r > 0.8, p < 0.001). CONCLUSION: Fractional calcium absorption can be estimated by a single oral tracer method using either radioactive or stable calcium isotopes across the entire age spectrum in healthy white adult women.

Integration of cell cycle control with transcriptional regulation by the retinoblastoma protein.

Rapid progress in several areas of molecular biology has led to the realization that the retinoblastoma protein may play a pivotal role in the coordination between cell cycle control and regulation of gene expression. This role is a subtle one, and is important in only certain mammalian cell types. Exploring the details of these connections, and why only some cells rely on them, is already beginning to shed light on the regulation of cell multiplication.

Grafted cerebellar cells in a mouse model of hereditary ataxia express IGF-I system genes and partially restore behavioral function.

Fetal grafts of normal cerebellar tissue were implanted into the cerebellum of Purkinje cell degeneration mutant mice (pcd/pcd), a model of adult-onset recessively inherited cerebello-olivary atrophy, in an attempt at correcting their cellular and motor impairment. Donor cerebellar cells engrafted in the appropriate sites, as evidenced by the pattern of expression of insulin-like growth factor-I (IGF-I) system genes. Bilateral cerebellar grafts led to an improvement of motor behaviors in balance rod tests and in the open field, providing evidence for functional integration into the atrophic mouse cerebellum and underscoring the potential of neural transplantation for counteracting the human cerebellar ataxias.

Adenovirus-mediated retinoblastoma gene therapy suppresses spontaneous pituitary melanotroph tumors in Rb+/- mice.

The retinoblastoma gene (RB) is the prototypic tumor suppressor. Studies to date have demonstrated cancer suppression with tumor cells reconstituted with RB ex vivo and implanted into immunodeficient mice, as well as with germline transmission of a human RB transgene into tumor-prone Rb +/- mice. To mimic the therapy of cancer more closely, spontaneous pituitary melanotroph tumors arising in immunocompetent Rb +/- mice were treated with a recombinant adenovirus carrying RB cDNA. Intratumoral RB gene transfer decreased tumor cell proliferation, reestablished innervation by growth-regulatory dopaminergic neurons, inhibited the growth of tumors, and prolonged the life spans of treated animals.

Immune receptor expressed on myeloid cells 1 (IREM-1) inhibits B cell activation factor (BAFF)-mediated inflammatory regulation of THP-1 cells through modulation of the activities of extracellular regulated kinase (ERK).

The immune receptor expressed on myeloid cells 1 (IREM-1) has been known to regulate the activities of myeloid cells through its immunoreceptor tyrosine-based inhibition motifs (ITIMs) in its intracellular region. In order to investigate its effect on macrophage activation, a human macrophage cell line (THP-1) was tested after stimulation of its membrane-bound form of B cell activation factor (BAFF), which has been shown to modulate inflammatory activities through induction of proinflammatory mediator expression and suppression of phagocytosis. IREM-1-specific monoclonal antibodies detected the expression of high levels of IREM-1 in THP-1 cells. Cross-linking of IREM-1 with these antibodies resulted in the blockage of the BAFF-mediated expression of interleukin (IL)-8 and matrix metalloproteinase (MMP)-9 through inhibition of the activation of extracellular regulated kinase (ERK) and phosphorylation/degradation of IκB. Furthermore, cross-linking of IREM-1 also reversed the BAFF-mediated inhibition of phagocytosis. In order to demonstrate the role of ITIM in the IREM-1-mediated suppression of BAFF signalling, a decapeptide containing YADL (an ITIM in IREM-1) was fused with HIV-TAT(48-57) which was required for the internalization of the synthetic polypeptide (TAT-YADL). TAT-YADL, but not control peptides, recapitulated the effect of the anti-IREM-1 monoclonal antibody. These observations indicate that IREM-1 exerted its inhibitory effect on BAFF-medicated signalling through ITIM-mediated regulation of ERK activities in THP-1 cells.