Spin-orbit torque switching of an antiferromagnetic metallic heterostructure.

The ability to represent information using an antiferromagnetic material is attractive for future antiferromagnetic spintronic devices. Previous studies have focussed on the utilization of antiferromagnetic materials with biaxial magnetic anisotropy for electrical manipulation. A practical realization of these antiferromagnetic devices is limited by the requirement of material-specific constraints. Here, we demonstrate current-induced switching in a polycrystalline PtMn/Pt metallic heterostructure. A comparison of electrical transport measurements in PtMn with and without the Pt layer, corroborated by x-ray imaging, reveals reversible switching of the thermally-stable antiferromagnetic Néel vector by spin-orbit torques. The presented results demonstrate the potential of polycrystalline metals for antiferromagnetic spintronics.

Comparing the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria for systemic lupus erythematosus (SLE) classification: which enables earlier classification of SLE in an urban Asian population?

OBJECTIVE: We compared the 1997 update of the 1982 American College of Rheumatology (ACR-97) and the 2012 Systemic Lupus International Collaborating Clinics (SLICC-12) criteria, for earlier classification of systemic lupus erythematosus (SLE) in a multiethnic urban Asian SLE population. METHODS: Patients from a retrospective, nested case-control study of the influence of lupus nephritis on mortality in SLE were studied. For each patient, dates of first manifestations of each criteria (both ACR-97 and SLICC-12) were recorded, and the date of disease classification using ACR-97 or SLICC-12 criteria was compared to determine which criteria resulted in earlier classification. RESULTS: Among 182 SLE patients (74.2% Chinese, 18.1% Malay, 4.4% Indian and 3.3% Other ethnicities), 10 (5.5%) did not fulfill the ACR-97 criteria and 2 (1.1%) did not fulfill the SLICC-12 criteria. Using the SLICC-12 criteria, 18% of subjects showed earlier classification, whereas 7% of subjects showed earlier classification using the ACR-97 criteria. The SLICC hematologic criteria of "Leukopenia or lymphopenia" contributed most significantly to earlier diagnosis by SLICC-12. "Leukopenia or lymphopenia'' was present in 59% (19/32) of patients where SLICC-12 criteria allowed for earlier classification than ACR-97, compared with 15.4% (2/13) of patients where ACR-97 allowed earlier classification than SLICC-12 ( p = 0.02). The immunologic criterion that is considered a strength of the SLICC-12 criteria did not appear to contribute significantly to earlier diagnosis in this study. CONCLUSION: SLICC-12 criteria allow for earlier classification of SLE in a multiethnic cohort of Asian patients, supporting the validity of the SLICC-12 criteria and its use in clinical care and research.

Crystal structure of 1-(5-bromo-1-benzo-furan-2-yl)ethanone oxime.

The title compound, C10H8BrNO2, is almost planar (r.m.s. deviation for the non-H atoms = 0.031 Å) and the conformation across the C=N bond is trans. Further, the O atom of the benzo-furan ring is syn to the N atom of the oxime group. In the crystal, inversion dimers linked by pairs of O-H⋯N hydrogen bonds generate R 2 (2)(6) loops. Very weak aromatic π-π stacking inter-actions [centroid-centroid separations = 3.9100 (12) and 3.9447 (12) Å] are also observed.

Perceived Benefits, Facilitators, Disadvantages, and Barriers for Physical Activity Amongst South Asian Adolescents in India and Canada.

OBJECTIVES: The purpose of this study was to understand perceived benefits, facilitators, disadvantages, and barriers for physical activity among South Asian adolescents in India and Canada. METHODS: Thirteen focus group discussions with South Asian (origin) adolescent boys and girls of different nutritional status and socioeconomic status in rural and urban India and urban Canada. RESULTS: Across the groups, fitness and 'energy' were perceived to be major benefits of physical activity. In India, better academic performance was highlighted, while health benefits were well detailed in Canadian groups. In all settings, friends, family, and teachers were perceived as facilitators of as well as barriers to physical activity. Lack of a safe space to play was a major concern for urban adolescents, while academic pressures and preference for other sedentary recreational activities were common barriers across all groups. Girls were less likely than boys to be interested in physical activity, with girls' participation in India further limited by societal restrictions. CONCLUSION: The study suggests key areas for promotion of physical activity among South Asian adolescents: balance between academic pressure and opportunities for physical activity, especially in India; urban planning for a built environment conducive to physical activity; and gender-sensitive programming to promote girls' activity which also addresses culture-specific barriers.

Toll-like receptor responses to Peste des petits ruminants virus in goats and water buffalo.

Ovine rinderpest or goat plague is an economically important and contagious viral disease of sheep and goats, caused by the Peste des petits ruminants virus (PPRV). Differences in susceptibility to goat plague among different breeds and water buffalo exist. The host innate immune system discriminates between pathogen associated molecular patterns and self antigens through surveillance receptors known as Toll like receptors (TLR). We investigated the role of TLR and cytokines in differential susceptibility of goat breeds and water buffalo to PPRV. We examined the replication of PPRV in peripheral blood mononuclear cells (PBMC) of Indian domestic goats and water buffalo and demonstrated that the levels of TLR3 and TLR7 and downstream signalling molecules correlation with susceptibility vs resistance. Naturally susceptible goat breeds, Barbari and Tellichery, had dampened innate immune responses to PPRV and increased viral loads with lower basal expression levels of TLR 3/7. Upon stimulation of PBMC with synthetic TLR3 and TLR7 agonists or PPRV, the levels of proinflammatory cytokines were found to be significantly higher while immunosuppressive interleukin (IL) 10 levels were lower in PPRV resistant Kanni and Salem Black breeds and water buffalo at transcriptional level, correlating with reduced viralloads in infected PBMC. Water buffalo produced higher levels of interferon (IFN) α in comparison with goats at transcriptional and translational levels. Pre-treatment of Vero cells with human IFNα resulted in reduction of PPRV replication, confirming the role of IFNα in limiting PPRV replication. Treatment with IRS66, a TLR7 antagonist, resulted in the reduction of IFNα levels, with increased PPRV replication confirming the role of TLR7. Single nucleotide polymorphism analysis of TLR7 of these goat breeds did not show any marked nucleotide differences that might account for susceptibility vs resistance to PPRV. Analyzing other host genetic factors might provide further insights on susceptibility to PPRV and genetic polymorphisms in the host.

2-(6-Hy-droxy-1-benzo-furan-3-yl)acetamide.

In the title compound, C10H9NO3, the dihedral angle between the benzo-furan ring system (r.m.s. deviation for the non-H atoms = 0.009 Å) and the -C-C(O)-N- segment is 83.76 (1)°. In the crystal, mol-ecules are linked by N-H⋯O and O-H⋯O hydrogen bonds, generating (001) sheets, which feature C(4) and C(10) chains.

Crystal structure of ethyl (6-hy-droxy-1-benzo-furan-3-yl)acetate sesquihydrate.

In the title hydrate, C12H12O4·1.5H2O, one of the water mol-ecules in the asymmetric unit is located on a twofold rotation axis. The mol-ecule of the benzo-furan derivative is essentially planar (r.m.s. deviation for the non-H atoms = 0.021 Å), with the ester group adopting a fully extended conformation. In the crystal, O-H⋯O hydrogen bonds between the water mol-ecules and the hy-droxy groups generate a centrosymmetric R 6 (6)(12) ring motif. These R 6 (6)(12) rings are fused, forming a one-dimensional motif extending along the c-axis direction.

Regulation of CD38 expression in human airway smooth muscle cells: role of class I phosphatidylinositol 3 kinases.

The ADP-ribosyl cyclase activity of CD38 generates cyclic ADP-ribose, a Ca(2+)-mobilizing agent. In human airway smooth muscle (HASM) cells, TNF-α mediates CD38 expression through mitogen-activated protein kinases and NF-κB and AP-1. The phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway is involved in TNF-α signaling and contributes to airway hyperresponsiveness and airway remodeling. We hypothesized that PI3Ks mediate CD38 expression and are involved in the differential induction of CD38 by TNF-α in asthmatic HASM cells. HASM cells were treated with pan-PI3K inhibitors (LY294002 or wortmannin) or class I-selective (GDC0941) or isoform-selective PI3K inhibitors (p110α-PIK-75 and p110ß-TGX-221) with or without TNF-α. HASM cells were transfected with a catalytically active form of PI3K or phosphatase and tensin homolog (PTEN) or nontargeting or p110 isoform-targeting siRNAs before TNF-α exposure. CD38 expression and activation of Akt, NF-κB, and AP-1 were determined. LY294002 and wortmannin inhibited TNF-α-induced Akt activation, whereas only LY294002 inhibited CD38 expression. P110 expression caused Akt activation and basal and TNF-α-induced CD38 expression, whereas PTEN expression attenuated Akt activation and CD38 expression. Expression levels of p110 isoforms α, ß, and δ were comparable in nonasthmatic and asthmatic HASM cells. Silencing of p110α or -δ, but not p110ß, resulted in comparable attenuation of TNF-α-induced CD38 expression in asthmatic and nonasthmatic cells. NF-κB and AP-1 activation were unaltered by the PI3K inhibitors. In HASM cells, regulation of CD38 expression occurs by specific class I PI3K isoforms, independent of NF-κB or AP-1 activation, and PI3K signaling may not be involved in the differential elevation of CD38 in asthmatic HASM cells.

Genotypic and pathotypic characterization of Newcastle disease viruses from India.

Newcastle disease virus (NDV) is an avian paramyxovirus that causes significant economic losses to the poultry industry in most parts of the world. The susceptibility of a wide variety of avian species coupled with synanthropic bird reservoirs has contributed to the vast genomic diversity of this virus as well as diagnostic failures. Since the first panzootic in 1926, Newcastle disease (ND) became enzootic in India with recurrent outbreaks in multiple avian species. The genetic characteristics of circulating strains in India, however, are largely unknown. To understand the nature of NDV genotypes in India, we characterized two representative strains isolated 13 years apart from a chicken and a pigeon by complete genome sequence analysis and pathotyping. The viruses were characterized as velogenic by pathogenicity indices devised to distinguish these strains. The genome length was 15,186 nucleotides (nt) and consisted of six non-overlapping genes, with conserved and complementary 3' leader and 5' trailer regions, conserved gene starts, gene stops, and intergenic sequences similar to those in avian paramyxovirus 1 (APMV-1) strains. Matrix gene sequence analysis grouped the pigeon isolate with APMV-1 strains. Phylogeny based on the fusion (F), and hemagglutinin (HN) genes and complete genome sequence grouped these viruses into genotype IV. Genotype IV strains are considered to have "died out" after the first panzootic (1926-1960) of ND. But, our results suggest that there is persistence of genotype IV strains in India.

Regulation of the cd38 promoter in human airway smooth muscle cells by TNF-alpha and dexamethasone.

BACKGROUND: CD38 is expressed in human airway smooth muscle (HASM) cells, regulates intracellular calcium, and its expression is augmented by tumor necrosis factor alpha (TNF-alpha). CD38 has a role in airway hyperresponsiveness, a hallmark of asthma, since deficient mice develop attenuated airway hyperresponsiveness compared to wild-type mice following intranasal challenges with cytokines such as IL-13 and TNF-alpha. Regulation of CD38 expression in HASM cells involves the transcription factor NF-kappaB, and glucocorticoids inhibit this expression through NF-kappaB-dependent and -independent mechanisms. In this study, we determined whether the transcriptional regulation of CD38 expression in HASM cells involves response elements within the promoter region of this gene. METHODS: We cloned a putative 3 kb promoter fragment of the human cd38 gene into pGL3 basic vector in front of a luciferase reporter gene. Sequence analysis of the putative cd38 promoter region revealed one NF-kappaB and several AP-1 and glucocorticoid response element (GRE) motifs. HASM cells were transfected with the 3 kb promoter, a 1.8 kb truncated promoter that lacks the NF-kappaB and some of the AP-1 sites, or the promoter with mutations of the NF-kappaB and/or AP-1 sites. Using the electrophoretic mobility shift assays, we determined the binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-kappaB, AP-1, and GRE sites, and the specificity of this binding was confirmed by gel supershift analysis with appropriate antibodies. RESULTS: TNF-alpha induced a two-fold activation of the 3 kb promoter following its transfection into HASM cells. In cells transfected with the 1.8 kb promoter or promoter constructs lacking NF-kappaB and/or AP-1 sites or in the presence of dexamethasone, there was no induction in the presence of TNF-alpha. The binding of nuclear proteins to oligonucleotides encoding the putative cd38 NF-kappaB site and some of the six AP-1 sites was increased by TNF-alpha, and to some of the putative cd38 GREs by dexamethasone. CONCLUSION: The EMSA results and the cd38 promoter-reporter assays confirm the functional role of NF-kappaB, AP-1 and GREs in the cd38 promoter in the transcriptional regulation of CD38.

Inflammatory aspects of sleep apnea and their cardiovascular consequences.

Obstructive sleep apnea (OSA) is a common medical condition that occurs in a considerable percentage of the population. Substantial evidence shows that patients with OSA have an increased incidence of hypertension compared with individuals without OSA, and that OSA is a risk factor for the development of hypertension. It is established that OSA may be implicated in stroke and transient ischemic attacks. OSA is associated with coronary heart disease, heart failure, and cardiac arrhythmias. Pulmonary hypertension may be associated with OSA, especially in patients with pre-existing pulmonary disease. Although the exact cause that links OSA with cardiovascular disease is unknown, there is evidence that OSA is associated with a group of proinflammatory and prothrombotic factors that have been identified as important in the development of atherosclerosis. OSA is associated with increased daytime and nocturnal sympathetic activity. Autonomic abnormalities seen in patients with OSA include increased resting heart rate, decreased R-R interval variability, and increased blood pressure variability. Both atherosclerosis and OSA are associated with endothelial dysfunction, increased C-reactive protein, interleukin 6, fibrinogen, plasminogen activator inhibitor, and reduced fibrinolytic activity. OSA has been associated with enhanced platelet activity and aggregation. Leukocyte adhesion and accumulation on endothelial cells are common in both OSA and atherosclerosis. Clinicians should be aware that OSA may be a risk factor for the development of cardiovascular disease.

Moraxella catarrhalis induces mast cell activation and nuclear factor kappa B-dependent cytokine synthesis.

Human mast cells are often found perivascularly and at mucosal sites and may play crucial roles in the inflammatory response. Recent studies have suggested a prominent role for mast cells in host defense. In this study, we analyzed the effects of a common airway pathogen, Moraxella catarrhalis and a commensal bacterium, Neiserria cinerea, on activation of human mast cells. Human mast cell leukemia cells (HMC-1) were activated with either phorbol myristate acetate (PMA) and calcium ionophore or with varying concentrations of heat-killed suspensions of bacteria. Supernatants were assayed for the cytokines interleukin-4 (IL-4), granulocyte macrophage colony stimulating factor (GM-CSF), IL-6, IL-8, IL-13 and monocyte chemotactic protein-1 (MCP-1). Nuclear proteins were isolated and assayed by electrophoretic mobility shift assay (EMSA) for nuclear factor kappaB (NF-kappaB) nuclear binding activity. In some experiments, NF-kappaB inhibitor, Bay-11 was added to determine functional significance. Both M. catarrhalis and N. cinerea induced mast cell activation and selective secretion of two key inflammatory cytokines, IL-6 and MCP-1. This was accompanied by NF-kappaB activation. Neither spun bacterial supernatants nor bacterial lipopolysaccharide induced cytokine secretion, suggesting need for direct bacterial contact with mast cells. Scanning electron microscopy revealed active aggregation of bacteria over mast cell surfaces. The NF-kappaB inhibitor, Bay-11, inhibited expression of MCP-1. These findings suggest the possibility of direct interactions between human mast cells and common bacteria and provide evidence for a novel role for human mast cells in innate immunity.

Insulin: a novel factor in carcinogenesis.

Cancer is a leading cause of mortality in the United States. Despite much research on specific carcinogens, the cause of many cancers remains unclear. The identification of novel causative agents offers the potential for cancer prevention. Diseases such as obesity and diabetes mellitus, characterized by hyperinsulinemia, are associated with increased risk of endometrial, colorectal, and breast carcinomas. There is increasing evidence that insulin is a growth factor for tumor formation. The mechanisms underlying insulin-mediated neoplasia may include enhanced DNA synthesis with resultant tumor cell growth, inhibition of apoptosis, and altered sex hormone milieu. The reduced insulin levels seen with physical activity, weight loss, and a high fiber diet may account for decreased cancer risk. The role of newer drugs that restore sensitivity to insulin, thereby reducing hyperinsulinemia, is an exciting potential area of cancer prevention. In this review, we discuss the potential role of insulin as a tumor growth factor.

Identification of a novel cytokine, ML-1, and its expression in subjects with asthma.

A novel gene, designated ML-1, was identified from a human genomic DNA clone and human T cell cDNA sequences. The second exon of ML-1 gene shares significant sequence identity with the gene encoding IL-17 (IL-17). ML-1 gene expression was up-regulated in activated PBMCs, CD4(+) T cells, allergen-specific Th0, Th1, and Th2 clones, activated basophils, and mast cells. Increased expression of the ML-1 gene, but not IL-17, was seen following allergen challenge in four asthmatic subjects, suggesting its role in allergic inflammatory responses. ML-1 from transiently transfected COS-7 cells was able to induce gene expression and protein production for IL-6 and IL-8 (at 10 ng/ml of ML-1: for IL-6, 599.6 +/- 19.1 pg/ml; for IL-8, 1724.2 +/- 132.9 pg/ml; and at 100 ng/ml of ML-1: for IL-6, 1005.3 +/- 55.6 pg/ml; for IL-8, 4371.4 +/- 280.5 pg/ml; p < 0.05 for both doses vs baseline) in primary bronchial epithelial (PBE) cells. Furthermore, increased expression of ICAM-1 was found in ML-1-stimulated PBE cells (mean fluorescence intensity (MFI) = 31.42 +/- 4.39 vs baseline, MFI = 12.26 +/- 1.77, p < 0.05), a functional feature distinct from IL-17 (MFI = 11.07 +/- 1.22). This effect was not inhibited by a saturating amount of IL-17. These findings demonstrate that ML-1 is a novel cytokine with a distinct function, and suggest a different receptor for ML-1 on PBE cells.

The human mast cell: functions in physiology and disease.

Mast cells are multifunctional, tissue-dwelling cells capable of secreting a wide variety of mediators. They develop from bone marrow-derived progenitor cells, primed with stem cell factor (SCF), which mediates its actions by interacting with the SCF receptor or c-kit on the cell surface. Mast cells continue their maturation and differentiation in peripheral tissue, developing into two well described subsets of cells, MCT and MCTC cells, varying in content of tryptase and chymase as well as in immunobiology. Mast cells are activated by numerous stimuli, including antigen (acting via the high affinity IgE receptor, Fc?RI), superoxides, complement proteins, neuropeptides and lipoproteins resulting in activation and degranulation. Following activation, these cells express mediators such as histamine, leukotrienes and prostanoids, as well as proteases, and many cytokines and chemokines, pivotal to the genesis of an inflammatory response. Recent data suggests that mast cells may play an active role in such diverse diseases as atherosclerosis, malignancy, asthma, pulmonary fibrosis and arthritis. Mast cells directly interact with bacteria and appear to play a vital role in host defense against pathogens. Drugs, such as glucocorticoids, cyclosporine and cromolyn have been demonstrated to have inhibitory effects on mast cell degranulation or mediator release.

Treatment strategies for bronchial asthma: an update.

Advances in understanding the biomolecular basis of the disease's inflammatory and remodeling responses are offering new therapeutic choices--and sometimes new drug-delivery systems--in categories such as beta-agonists, glucocorticoids, and leukotriene blockers. Meanwhile, researchers are exploring novel targets, including intercellular signals and cell-adhesion and gene-activating molecules.

Reactive and clonal thrombocytosis: proinflammatory and hematopoietic cytokines and acute phase proteins.

BACKGROUND: We quantitated proinflammatory and thrombopoietic cytokines in reactive thrombocytosis (RT) and clonal thrombocytosis (CT) to identify a cytokine profile that might aid in the distinction of these two disorders. METHODS: Serum levels of cytokines relevant to platelet biology--interleukins 3, 6, 11, and 1beta; thrombopoietin; tumor necrosis factor alpha; and C-reactive protein (CRP)--were measured by enzyme-linked immunosorbent assay in healthy subjects and in patients with CT and RT. RESULTS: Interleukin-6 and CRP levels were higher in RT patients than in controls or CT patients. Interleukin 1beta levels were higher in the RT group than in the CT and control groups. CONCLUSIONS: In RT, IL-6, IL-1beta, and CRP levels are elevated. In both RT and CT, IL-11 is elevated, but thrombopoietin levels are not.

Acute and chronic urticaria. Challenges and considerations for primary care physicians.

Urticaria and angioedema are common dermatologic problems seen by primary care physicians. A carefully taken history, physical examination, specific tests, and skin biopsy often provide useful diagnostic information. In patients with chronic urticaria, urticarial vasculitis and diseases that mimic urticaria need to be ruled out. A variety of treatment options are available for patients with urticaria and urticarial vasculitis. Pharmacologic therapy is useful when the specific cause is undetermined. When a trigger has been identified, the patient must avoid exposure to it. Patient education is an important component of management and should include instructions on crisis management, particularly for patients who have angioedema or a tendency for anaphylaxis.

Difficult-to-manage asthma. How to pinpoint the exacerbating factors.

In difficult-to-manage asthma, effective control depends on identification and alleviation of exacerbating factors, such as ongoing allergen exposure, chronic sinusitis, GERD, and emotional stress. Level of compliance with the prescribed medication regimen should be evaluated in all patients. Hormonal factors (i.e., menses, use of exogenous hormones by female patients, and hyperthyroidism) also can exacerbate asthma. When aggressive management fails, the possibility of a misdiagnosis should be considered. Other conditions that can mimic asthma include COPD, congestive heart failure, airway obstruction due to various causes, vocal cord dysfunction, and esophageal spasm. Referral to an asthma specialist is advised in severe or resistant cases.