Projectively Enriched Symmetry and Topology in Acoustic Crystals.

Symmetry plays a key role in modern physics, as manifested in the revolutionary topological classification of matter in the past decade. So far, we seem to have a complete theory of topological phases from internal symmetries as well as crystallographic symmetry groups. However, an intrinsic element, i.e., the gauge symmetry in physical systems, has been overlooked in the current framework. Here, we show that the algebraic structure of crystal symmetries can be projectively enriched due to the gauge symmetry, which subsequently gives rise to new topological physics never witnessed under ordinary symmetries. We demonstrate the idea by theoretical analysis, numerical simulation, and experimental realization of a topological acoustic lattice with projective translation symmetries under a Z_{2} gauge field, which exhibits unique features of rich topologies, including a single Dirac point, Möbius topological insulator, and graphenelike semimetal phases on a rectangular lattice. Our work reveals the impact when gauge and crystal symmetries meet together with topology and opens the door to a vast unexplored land of topological states by projective symmetries.

Accuracy in Facial Trustworthiness Impressions: Kernel of Truth or Modern Physiognomy? A Meta-Analysis.

Being able to identify trustworthy strangers is a critical social skill. However, whether such impressions are accurate is debatable. Critically, the field currently lacks a quantitative summary of the evidence. To address this gap, we conducted two meta-analyses. We tested whether there is a correlation between perceived and actual trustworthiness across faces, and whether perceivers show above-chance accuracy at assessing trustworthiness. Both meta-analyses revealed significant, modest accuracy (face level, r = .14; perceiver level, r = .27). Perceiver-level effects depended on domain, with aggressiveness and sexual unfaithfulness having stronger effects than agreeableness, criminality, financial reciprocity, and honesty. We also applied research weaving to map the literature, revealing potential biases, including a preponderance of Western studies, a lack of "cross-talk" between research groups, and clarity issues. Overall, this modest accuracy is unlikely to be of practical utility. Moreover, we strongly urge the field to improve reporting standards and generalizability of the results.

Cigarette smoke induces miR-132 in Th17 cells that enhance osteoclastogenesis in inflammatory arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by joint destruction and severe morbidity. Cigarette smoking (CS) can exacerbate the incidence and severity of RA. Although Th17 cells and the Aryl hydrocarbon receptor (AhR) have been implicated, the mechanism by which CS induces RA development remains unclear. Here, using transcriptomic analysis, we show that microRNA-132 is specifically induced in Th17 cells in the presence of either AhR agonist or CS-enriched medium. miRNA-132 thus induced is packaged into extracellular vesicles produced by Th17 and acts as a proinflammatory mediator increasing osteoclastogenesis through the down-regulation of COX2. In vivo, articular knockdown of miR-132 in murine arthritis models reduces the number of osteoclasts in the joints. Clinically, RA patients express higher levels of miR-132 than do healthy individuals. This increase is further elevated by cigarette smoking. Together, these results reveal a hitherto unrecognized mechanism by which CS could exacerbate RA and further advance understanding of the impact of environmental factors on the pathogenesis of chronic inflammatory diseases.

Attenuation of Dupuytren's fibrosis via targeting of the STAT1 modulated IL-13Rα1 response.

Fibrotic disorders represent common complex disease pathologies that are therapeutically challenging. Inflammation is associated with numerous fibrotic pathogeneses; however, its role in the multifaceted mechanisms of fibrosis remains unclear. IL-13 is implicated in aberrant responses involved in fibrotic disease, and we aimed to understand its role in the inflammatory processes of a common fibrotic disorder, Dupuytren's disease. We demonstrated T-cells produced IFN-g, which induced IL-13 secretion from mast cells and up-regulated IL-13Ra1 on fibroblasts, rendering them more reactive to IL-13. Consequently, diseased myofibroblasts demonstrated enhanced fibroproliferative effects upon IL-13 stimulation. We established IFN-g and IL-13 responses involved STAT dependent pathways, and STAT targeting (tofacitinib) could inhibit IL-13 production from mast cells, IL-13Ra1 up-regulation in fibroblasts and fibroproliferative effects of IL-13 on diseased myofibroblasts. Accordingly, utilizing Dupuytren's as an accessible human model of fibrosis, we propose targeting STAT pathways may offer previously unidentified therapeutic approaches in the management of fibrotic disease.

Identification of Antibacterial Molecule(s) from Animals Living in Polluted Environments.

BACKGROUND: Snakes feed on germ-infested rodents, while water monitor lizards thrive on rotten matter in unhygienic conditions. We hypothesize that such creatures survive the assault of superbugs and are able to fend off disease by producing antimicrobial substances. In this study, we investigated the potential antibacterial activity of sera/lysates of animals living in polluted environments. METHODS: Snake (Reticulatus malayanus), rats (Rattus rattus), water monitor lizard (Varanus salvator), frog (Lithobates catesbeianus), fish (Oreochromis mossambicus), chicken (Gallus gallus domesticus), and pigeon (Columba livia) were dissected and their organ lysates/sera were collected. Crude extracts were tested for bactericidal effects against neuropathogenic E. coli K1, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Bacillus cereus and Klebsiella pneumoniae. To determine whether lysates/sera protect human cells against bacterialmediated damage, cytotoxicity assays were performed by measuring lactate dehydrogenase release as an indicator of cell death. Lysates/sera were partially characterized using heat-treatment and pronasetreatment and peptide sequences were determined using the Liquid Chromatography Mass Spectrometry (LC-MS). RESULTS: Snake and water monitor lizard sera exhibited potent broad-spectrum bactericidal effects against all bacteria tested. Heat inactivation and pronase-treatment inhibited bactericidal effects indicating that activity is heat-labile and pronase-sensitive suggesting that active molecules are proteinaceous in nature. LCMS analyses revealed the molecular identities of peptides. CONCLUSION: The results revealed that python that feeds on germ-infested rodents and water monitor lizards that feed on rotten organic waste possess antibacterial activity in a heat-sensitive manner and several peptides were identified. We hope that the discovery of antibacterial activity in the sera of animals living in polluted environments will stimulate research in finding antibacterial agents from unusual sources as this has the potential for the development of novel strategies in the control of infectious diseases.

Neutrophil extracellular traps (NETs) exacerbate severity of infant sepsis.

BACKGROUND: Neutrophil extracellular traps (NETs) are innate defense mechanisms that are also implicated in the pathogenesis of organ dysfunction. However, the role of NETs in pediatric sepsis is unknown. METHODS: Infant (2 weeks old) and adult (6 weeks old) mice were submitted to sepsis by intraperitoneal (i.p.) injection of bacteria suspension or lipopolysaccharide (LPS). Neutrophil infiltration, bacteremia, organ injury, and concentrations of cytokine, NETs, and DNase in the plasma were measured. Production of reactive oxygen and nitrogen species and release of NETs by neutrophils were also evaluated. To investigate the functional role of NETs, mice undergoing sepsis were treated with antibiotic plus rhDNase and the survival, organ injury, and levels of inflammatory markers and NETs were determined. Blood samples from pediatric and adult sepsis patients were collected and the concentrations of NETs measured. RESULTS: Infant C57BL/6 mice subjected to sepsis or LPS-induced endotoxemia produced significantly higher levels of NETs than the adult mice. Moreover, compared to that of the adult mice, this outcome was accompanied by increased organ injury and production of inflammatory cytokines. The increased NETs were associated with elevated expression of Padi4 and histone H3 citrullination in the neutrophils. Furthermore, treatment of infant septic mice with rhDNase or a PAD-4 inhibitor markedly attenuated sepsis. Importantly, pediatric septic patients had high levels of NETs, and the severity of pediatric sepsis was positively correlated with the level of NETs. CONCLUSION: This study reveals a hitherto unrecognized mechanism of pediatric sepsis susceptibility and suggests that NETs represents a potential target to improve clinical outcomes of sepsis.

CCR5-Positive Inflammatory Monocytes are Crucial for Control of Sepsis.

Neutrophils and inflammatory monocytes control sepsis by migration to the site of infection via their chemokine receptors. CCR5 is a chemokine receptor that is not expressed on neutrophils and inflammatory monocytes under homeostatic conditions. However, it has been demonstrated that CCR5 can become expressed on these cells during different models of inflammation. In the present study, we investigated if CCR5 is also expressed on neutrophil and inflammatory monocytes during sepsis, exerting an important role in the migration of these cells to the infectious focus. Using cecal ligation and puncture model to induce polymicrobial sepsis, we demonstrated that the expression of CCR5 is induced on CD11bLy6GLy6C inflammatory monocytes, but not on neutrophils (CD11bLy6GLy6C). Furthermore, CCR5 plays an important role for the migration of the inflammatory monocytes to infection focus during sepsis. CCR5-expressing inflammatory monocytes migrate from the bone marrow to the circulation and then into the site of infection, where they phagocytize and kill the bacteria. Consequently, CCR5 mice showed increased systemic inflammatory response and mortality compared to wild-type mice. These data therefore demonstrate a hitherto unrecognized protective role of CCR5 in sepsis.

Interleukin-33 contributes to disease severity in Dengue virus infection in mice.

The excessive inflammation often present in patients with severe dengue infection is considered both a hallmark of disease and a target for potential treatments. Interleukin-33 (IL-33) is a pleiotropic cytokine with pro-inflammatory effects whose role in dengue has not been fully elucidated. We demonstrate that IL-33 plays a disease-exacerbating role during experimental dengue infection in immunocompetent mice. Mice infected with dengue virus serotype 2 (DENV2) produced high levels of IL-33. DENV2-infected mice treated with recombinant IL-33 developed markedly more severe disease compared with untreated mice as assessed by mortality, granulocytosis, liver damage and pro-inflammatory cytokine production. Conversely, ST2-/- mice (deficient in IL-33 receptor) infected with DENV2 developed significantly less severe disease compared with wild-type mice. Furthermore, the increased disease severity and the accompanying pathology induced by IL-33 during dengue infection were reversed by the simultaneous treatment with a CXCR2 receptor antagonist (DF2156A). Together, these results indicate that IL-33 plays a disease-exacerbating role in experimental dengue infection, probably driven by CXCR2-expressing cells, leading to elevated pro-inflammatory response-mediated pathology. Our results also indicate that IL-33 is a potential therapeutic target for dengue infection.

Interleukin-33 Receptor (ST2) Deficiency Improves the Outcome of Staphylococcus aureus-Induced Septic Arthritis.

The ST2 receptor is a member of the Toll/IL-1R superfamily and interleukin-33 (IL-33) is its agonist. Recently, it has been demonstrated that IL-33/ST2 axis plays key roles in inflammation and immune mediated diseases. Here, we investigated the effect of ST2 deficiency in Staphylococcus aureus-induced septic arthritis physiopathology. Synovial fluid samples from septic arthritis and osteoarthritis individuals were assessed regarding IL-33 and soluble (s) ST2 levels. The IL-33 levels in samples from synovial fluid were significantly increased, whereas no sST2 levels were detected in patients with septic arthritis when compared with osteoarthritis individuals. The intra-articular injection of 1 × 107 colony-forming unity/10 µl of S. aureus American Type Culture Collection 6538 in wild-type (WT) mice induced IL-33 and sST2 production with a profile resembling the observation in the synovial fluid of septic arthritis patients. Data using WT, and ST2 deficient (-/-) and interferon-γ (IFN-γ)-/- mice showed that ST2 deficiency shifts the immune balance toward a type 1 immune response that contributes to eliminating the infection due to enhanced microbicide effect via NO production by neutrophils and macrophages. In fact, the treatment of ST2-/- bone marrow-derived macrophage cells with anti-IFN-γ abrogates the beneficial phenotype in the absence of ST2, which confirms that ST2 deficiency leads to IFN-γ expression and boosts the bacterial killing activity of macrophages against S. aureus. In agreement, WT cells achieved similar immune response to ST2 deficiency by IFN-γ treatment. The present results unveil a previously unrecognized beneficial effect of ST2 deficiency in S. aureus-induced septic arthritis.

Smoking-induced aggravation of experimental arthritis is dependent of aryl hydrocarbon receptor activation in Th17 cells.

BACKGROUND: Epidemiologic studies have highlighted the association of environmental factors with the development and progression of autoimmune and chronic inflammatory diseases. Among the environmental factors, smoking has been associated with increased susceptibility and poor prognosis in rheumatoid arthritis (RA). However, the immune and molecular mechanism of smoking-induced arthritis aggravation remains unclear. The transcription factor aryl hydrocarbon receptor (AHR) regulates the generation of Th17 cells, CD4 T cells linked the development of autoimmune diseases. AHR is activated by organic compounds including polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants that are also present in cigarette smoke. In this study, we investigated the role of AHR activation in the aggravation of experiment arthritis induced by exposure to cigarette smoke. METHODS: Mice were exposed to cigarette smoke during the developmental phase of antigen-induced arthritis and collagen-induced arthritis to evaluate the effects of smoking on disease development. Aggravation of articular inflammation was assessed by measuring neutrophil migration to the joints, increase in articular hyperalgesia and changes in the frequencies of Th17 cells. In vitro studies were performed to evaluate the direct effects of cigarette smoke and PAH on Th17 differentiation. We also used mice genetically deficient for AHR (Ahr KO) and IL-17Ra (Il17ra KO) to determine the in vivo mechanism of smoking-induced arthritis aggravation. RESULTS: We found that smoking induces arthritis aggravation and increase in the frequencies of Th17 cells. The absence of IL-17 signaling (Il17ra KO) conferred protection to smoking-induced arthritis aggravation. Moreover, in vitro experiments showed that cigarette smoke can directly increase Th17 differentiation of T cells by inducing AHR activation. Indeed, Ahr KO mice were protected from cigarette smoke-induced arthritis aggravation and did not display increase in TH17 frequencies, suggesting that AHR activation is an important mechanism for cigarette smoke effects on arthritis. Finally, we demonstrate that PAHs are also able to induce arthritis aggravation. CONCLUSIONS: Our data demonstrate that the disease-exacerbating effects of cigarette smoking are AHR dependent and environmental pollutants with AHR agonist activity can induce arthritis aggravation by directly enhancing Th17 cell development.

Targeting the IL33-NLRP3 axis improves therapy for experimental cerebral malaria.

Cerebral malaria (CM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently, the only treatment for CM is the provision of antimalarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify potential improved treatments for CM, we performed a nonbiased whole-brain transcriptomic time-course analysis of antimalarial drug chemotherapy of murine experimental CM (ECM). Bioinformatics analyses revealed IL33 as a critical regulator of neuroinflammation and cerebral pathology that is down-regulated in the brain during fatal ECM and in the acute period following treatment of ECM. Consistent with this, administration of IL33 alongside antimalarial drugs significantly improved the treatment success of established ECM. Mechanistically, IL33 treatment reduced inflammasome activation and IL1ß production in microglia and intracerebral monocytes in the acute recovery period following treatment of ECM. Moreover, treatment with the NLRP3-inflammasome inhibitor MCC950 alongside antimalarial drugs phenocopied the protective effect of IL33 therapy in improving the recovery from established ECM. We further showed that IL1ß release from macrophages was stimulated by hemozoin and antimalarial drugs and that this was inhibited by MCC950. Our results therefore demonstrate that manipulation of the IL33-NLRP3 axis may be an effective therapy to suppress neuroinflammation and improve the efficacy of antimalarial drug treatment of CM.

The Atypical Chemokine Receptor ACKR2 is Protective Against Sepsis.

Sepsis is a systemic inflammatory response as a result of uncontrolled infections. Neutrophils are the first cells to reach the primary sites of infection, and chemokines play a key role in recruiting neutrophils. However, in sepsis chemokines could also contribute to neutrophil infiltration to vital organs leading to multiple organ failure. ACKR2 is an atypical chemokine receptor, which can remove and degrade inflammatory CC chemokines. The role of ACK2 in sepsis is unknown. Using a model of cecal ligation and puncture (CLP), we demonstrate here that ACKR2 deficient () mice exhibited a significant reduction in the survival rate compared with similarly treated wild-type (WT) mice. However, neutrophil migration to the peritoneal cavity and bacterial load were similar between WT and ACKR2 mice during CLP. In contrast, ACKR2 mice showed increased neutrophil infiltration and elevated CC chemokine levels in the lung, kidney, and heart compared with the WT mice. In addition, ACKR2 mice also showed more severe lesions in the lung and kidney than those in the WT mice. Consistent with these results, WT mice under nonsevere sepsis (90% survival) had higher expression of ACKR2 in these organs than mice under severe sepsis (no survival). Finally, the lungs from septic patients showed increased number of ACKR2 cells compared with those of nonseptic patients. Our data indicate that ACKR2 may have a protective role during sepsis, and the absence of ACKR2 leads to exacerbated chemokine accumulation, neutrophil infiltration, and damage to vital organs.

TGF-ß signalling defect is linked to low CD39 expression on regulatory T cells and methotrexate resistance in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an autoimmune arthropathy characterized by chronic articular inflammation. Methotrexate (MTX) remains the first-line therapy for RA and its anti-inflammatory effect is associated with the maintenance of high levels of extracellular adenosine (ADO). Nonetheless, up to 40% of RA patients are resistant to MTX treatment and this is linked to a reduction of CD39 expression, an ectoenzyme involved in the generation of extracellular ADO by ATP metabolism, on circulating regulatory T cells (Tregs). However, the mechanism mediating the reduction of CD39 expression on Tregs is unknown. Here we demonstrated that the impairment in TGF-ß signalling lead to the reduction of CD39 expression on Tregs that accounts for MTX resistance. TGF-ß increases CD39 expression on Tregs via the activation of TGFBRII/TGFBRI, SMAD2 and the transcription factor CREB, which is activated in a p38-dependent manner and induces CD39 expression by promoting ENTPD1 gene transcription. Importantly, unresponsive patients to MTX (UR-MTX) show reduced expression of TGFBR2 and CREB1 and decreased levels of p-SMAD2 and p-CREB in Tregs compared to MTX-responsive patients (R-MTX). Furthermore, RA patients carrying at least one mutant allele for rs1431131 (AT or AA) of the TGFBR2 gene are significantly (p = 0.0006) associated with UR-MTX. Therefore, we have uncovered a molecular mechanism for the reduced CD39 expression on Tregs, and revealed potential targets for therapeutic intervention for MTX resistance.

IL-33 contributes to sepsis-induced long-term immunosuppression by expanding the regulatory T cell population.

Patients who survive sepsis can develop long-term immune dysfunction, with expansion of the regulatory T (Treg) cell population. However, how Treg cells proliferate in these patients is not clear. Here we show that IL-33 has a major function in the induction of this immunosuppression. Mice deficient in ST2 (IL-33R) develop attenuated immunosuppression in cases that survive sepsis, whereas treatment of naive wild-type mice with IL-33 induces immunosuppression. IL-33, released during tissue injury in sepsis, activates type 2 innate lymphoid cells, which promote polarization of M2 macrophages, thereby enhancing expansion of the Treg cell population via IL-10. Moreover, sepsis-surviving patients have more Treg cells, IL-33 and IL-10 in their peripheral blood. Our study suggests that targeting IL-33 may be an effective treatment for sepsis-induced immunosuppression.

M1-like monocytes are a major immunological determinant of severity in previously healthy adults with life-threatening influenza.

In each influenza season, a distinct group of young, otherwise healthy individuals with no risk factors succumbs to life-threatening infection. To better understand the cause for this, we analyzed a broad range of immune responses in blood from a unique cohort of patients, comprising previously healthy individuals hospitalized with and without respiratory failure during one influenza season, and infected with one specific influenza A strain. This analysis was compared with similarly hospitalized influenza patients with known risk factors (total of n = 60 patients recruited). We found a sustained increase in a specific subset of proinflammatory monocytes, with high TNF-α expression and an M1-like phenotype (independent of viral titers), in these previously healthy patients with severe disease. The relationship between M1-like monocytes and immunopathology was strengthened using murine models of influenza, in which severe infection generated using different models (including the high-pathogenicity H5N1 strain) was also accompanied by high levels of circulating M1-like monocytes. Additionally, a raised M1/M2 macrophage ratio in the lungs was observed. These studies identify a specific subtype of monocytes as a modifiable immunological determinant of disease severity in this subgroup of severely ill, previously healthy patients, offering potential novel therapeutic avenues.

Prevalence and factors associated with internet addiction among medical students - A cross-sectional study in Malaysia.

INTRODUCTION: Internet is important to university students, especially for medical students who use it to search for literature and relevant information. However, some of the users are experiencing a gradual loss of the ability to reduce the duration and frequency of their internet activities, despite the negative consequences. The literature on internet usage among Malaysian medical students is limited. This study aims to determine the prevalence and factors associated with internet usage among medical students in a public university in Malaysia. METHODS: This cross-sectional study was performed among all the medical students (Year 1-5). Students were assessed on their internet activities using the internet addiction questionnaires (IAT). A Multiple Logistic Regression was used for data analysis. RESULTS: The study was conducted among 426 students. The study population consisted of 156 males (36.6%) and 270 females (63.4%). The mean age was 21.6 ±1.5 years. Ethnicity distribution among the students was: Malays (55.6%), Chinese (34.7%), Indians (7.3%) and others (2.3%). According to the IAT, 36.9% of the study sample was addicted to the internet. Using the multivariate logistic regression analysis, we have found that the use of internet access for entertainment purposes (odds ratio [OR] 3.5, 95% confidence interval [CI] 1.05-12.00), male students (OR 1.8, 95% CI 1.01-3.21) and increasing frequency of internet usage were associated with internet addiction (OR 1.4, 95% CI 1.09- 1.67). CONCLUSION: Internet addiction is a relatively frequent phenomenon among medical students. The predictors of internet addiction were male students using it for surfing and entertainment purposes.

IL-33 ameliorates Alzheimer's disease-like pathology and cognitive decline.

Alzheimer's disease (AD) is a devastating condition with no known effective treatment. AD is characterized by memory loss as well as impaired locomotor ability, reasoning, and judgment. Emerging evidence suggests that the innate immune response plays a major role in the pathogenesis of AD. In AD, the accumulation of ß-amyloid (Aß) in the brain perturbs physiological functions of the brain, including synaptic and neuronal dysfunction, microglial activation, and neuronal loss. Serum levels of soluble ST2 (sST2), a decoy receptor for interleukin (IL)-33, increase in patients with mild cognitive impairment, suggesting that impaired IL-33/ST2 signaling may contribute to the pathogenesis of AD. Therefore, we investigated the potential therapeutic role of IL-33 in AD, using transgenic mouse models. Here we report that IL-33 administration reverses synaptic plasticity impairment and memory deficits in APP/PS1 mice. IL-33 administration reduces soluble Aß levels and amyloid plaque deposition by promoting the recruitment and Aß phagocytic activity of microglia; this is mediated by ST2/p38 signaling activation. Furthermore, IL-33 injection modulates the innate immune response by polarizing microglia/macrophages toward an antiinflammatory phenotype and reducing the expression of proinflammatory genes, including IL-1ß, IL-6, and NLRP3, in the cortices of APP/PS1 mice. Collectively, our results demonstrate a potential therapeutic role for IL-33 in AD.

Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain.

Neuropathic pain from injury to the peripheral and CNS represents a major health care issue. We have investigated the role of IL-33/IL-33 receptor (ST2) signaling in experimental models of neuropathic pain in mice. Chronic constriction injury (CCI) of the sciatic nerve induced IL-33 production in the spinal cord. IL-33/citrine reporter mice revealed that oligodendrocytes are the main cells expressing IL-33 within the spinal cord together with a minor expression by neurons, microglia. and astrocytes. CCI-induced mechanical hyperalgesia was reduced in IL-33R (ST2)(-/ -) mice compared with wild-type (WT) mice. Intrathecal treatment of WT mice with soluble IL-33 receptor (IL-33 decoy receptor) markedly reduced CCI-induced hyperalgesia. Consistent with these observations, intrathecal injection of IL-33 enhanced CCI hyperalgesia and induced hyperalgesia in naive mice. IL-33-mediated hyperalgesia during CCI was dependent on a reciprocal relationship with TNF-α and IL-1ß. IL-33-induced hyperalgesia was markedly attenuated by inhibitors of PI3K, mammalian target of rapamycin, MAPKs (p38, ERK, and JNK), NF-κB, and also by the inhibitors of glial cells (microglia and astrocytes). Furthermore, targeting these signaling pathways and cells inhibited IL-33-induced TNF-α and IL-1ß production in the spinal cord. Our study, therefore, reveals an important role of oligodendrocyte-derived IL-33 in neuropathic pain.

Resonance modulated amplified emission from CdSSe nanoribbons.

We present evidence of amplified emission mediated by surface plasmon polaritons (SPPs) from a CdS0.2Se0.8 nanoribbon (NR) supported on a gold-coated silicon substrate. Room temperature amplified emission is observed from the nanoribbon above excitation irradiances ~ 25 W/cm(2) when it is supported on the gold coated silicon substrate. The nanoribbon is shown to act as a resonator cavity, leading to amplification of discrete wavelengths in the emission spectrum. Evidence for the formation of SPP waves between the gold-coated substrate and the nanoribbon is shown, and the resulting wavenumber increase allows for the matching of theoretical resonance wavelengths with those observed experimentally.

MicroRNA29a regulates IL-33-mediated tissue remodelling in tendon disease.

MicroRNA (miRNA) has the potential for cross-regulation and functional integration of discrete biological processes during complex physiological events. Utilizing the common human condition tendinopathy as a model system to explore the cross-regulation of immediate inflammation and matrix synthesis by miRNA we observed that elevated IL-33 expression is a characteristic of early tendinopathy. Using in vitro tenocyte cultures and in vivo models of tendon damage, we demonstrate that such IL-33 expression plays a pivotal role in the transition from type 1 to type 3 collagen (Col3) synthesis and thus early tendon remodelling. Both IL-33 effector function, via its decoy receptor sST2, and Col3 synthesis are regulated by miRNA29a. Downregulation of miRNA29a in human tenocytes is sufficient to induce an increase in Col3 expression. These data provide a molecular mechanism of miRNA-mediated integration of the early pathophysiologic events that facilitate tissue remodelling in human tendon after injury.