Thy-1 Attenuates TNF-α-Activated Gene Expression in Mouse Embryonic Fibroblasts via Src Family Kinase

Heterogeneous surface expression of Thy-1 in fibroblasts modulates inflammation and may thereby modulate injury and repair. As a paradigm, patients with idiopathic pulmonary fibrosis, a disease with pathologic features of chronic inflammation, demonstrate an absence of Thy-1 immunoreactivity within areas of fibrotic activity (fibroblast foci) in contrast to the predominant Thy-1 expressing fibroblasts in the normal lung. Likewise, Thy-1 deficient mice display more severe lung fibrosis in response to an inflammatory injury than wildtype littermates. We investigated the role of Thy-1 in the response of fibroblasts to the pro-inflammatory cytokine TNF-α. Our study demonstrates distinct profiles of TNF-α-activated gene expression in Thy-1 positive (Thy-1+) and negative (Thy-1−) subsets of mouse embryonic fibroblasts (MEF). TNF-α induced a robust activation of MMP-9, ICAM-1, and the IL-8 promoter driven reporter in Thy-1− MEFs, in contrast to only a modest increase in Thy-1+ counterparts. Consistently, ectopic expression of Thy-1 in Thy-1− MEFs significantly attenuated TNF-α-activated gene expression. Mechanistically, TNF-α activated Src family kinase (SFK) only in Thy-1− MEFs. Blockade of SFK activation abrogated TNF-α-activated gene expression in Thy-1− MEFs, whereas restoration of SFK activation rescued the TNF-α response in Thy-1+ MEFs. Our findings suggest that Thy-1 down-regulates TNF-α-activated gene expression via interfering with SFK- and NF-κB-mediated transactivation. The current study provides a novel mechanistic insight to the distinct roles of fibroblast Thy-1 subsets in inflammation

Association between long travel and venous thromboembolic disease: a systematic review and meta-analysis of case-control studies

The term “economy-class syndrome” defines an infrequent episode of venous thromboembolism (VTED) related to a long travel, namely by plane. However, this relation has not clearly been demonstrated by investigators. We carried out a systematic review and a meta-analysis of cases-control studies that had studied this topic. We realised a systematic review of the literature and selected all the case-control studies published. Two authors carried out a methodological evaluation according to the Scottish Intercollegiate Guidelines Network items (concordance was analysed by weighted kappa index), and a systematic analysis of the potential biases of each study was assessed. We carried out the meta-analysis with the data extracted from the studies. We recovered eight cases-control studies. The relation between the antecedent of a long travel and subsequent VTED varied from OR = 1.1 to OR = 4.0 and was found to be significant in four studies. The studies were highly heterogeneous in methodology and so the results obtained about the relation between the long travel and the VTED and the score at SIGN50. Two meta-analysis were carried out: only with travels by plane in which the relation was not significant (OR = 1.21; CI 95%, 0.95–1.55) and with all types of transport, with a slightly significant relation (OR = 1.46; CI95%, 1.24–1.72). We may deduce from this systematic review that there does exist a weak association between episodes of VTED and a long travel, but not by plane specifically. The heterogeneity and the methodological quality of the studies published preclude of more robust conclusions

A cognitive framework for object recognition with application to autonomous vehicles

Autonomous vehicles or self-driving cars are capable of sensing the surrounding environment so they can navigate roads without human input. Decisions are constantly made on sensing, mapping and driving policy using machine learning techniques. Deep Learning – massive neural networks that utilize the power of parallel processing – has become a popular choice for addressing the complexities of real time decision making. This method of machine learning has been shown to outperform alternative solutions in multiple domains, and has an architecture that can be adapted to new problems with relative ease. To harness the power of Deep Learning, it is necessary to have large amounts of training data that are representative of all possible situations the system will face. To successfully implement situational awareness in driverless vehicles, it is not possible to exhaust all possible training examples. An alternative method is to apply cognitive approaches to perception, for situations the autonomous vehicles will face. Cognitive approaches to perception work by mimicking the process of human intelligence – thereby permitting a machine to react to situations it has not previously experienced. This paper proposes a novel cognitive approach for object recognition. The proposed cognitive object recognition algorithm, referred to as Recognition by Components, is inspired by the psychological studies pertaining to early childhood development. The algorithm works by breaking down images into a series of primitive forms such as square, triangle, circle or rectangle and memory based aggregation to identify objects. Experimental results suggest that Recognition by Component algorithm performs significantly better than algorithms that require large amounts of training data

Critical values of facet joint angulation and tropism in the development of lumbar degenerative spondylolisthesis: an international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

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Is lumbar facet joint tropism developmental or secondary to degeneration? An international, large-scale multicenter study by the AOSpine Asia Pacific Research Collaboration Consortium

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Acanthus montanus: An experimental evaluation of the antimicrobial, anti-inflammatory and immunological properties of a traditional remedy for furuncles

<p>Abstract</p> <p>Background</p> <p><it>Acanthus montanus </it>(Nees) T. Anderson (Acanthaceae) is a shrub widespread in Africa, the Balkans, Romania, Greece and Eastern Mediterranean. It is used in African traditional medicine for the treatment of urogenital infections, urethral pain, endometritis, urinary disease, cystitis, leucorrhoea, aches and pains. In southeastern Nigeria, the root is popular and acclaimed highly effective in the treatment of furuncles. This study was undertaken to experimentally evaluate the antimicrobial and anti-inflammatory properties of the root extract as well as its effect on phagocytosis and specific cell-mediated immune response which may underlie the usefulness of the roots in treatment of furuncles.</p> <p>Methods</p> <p>The aqueous root extract (obtained by hot water maceration of the root powder) was studied for effects on the growth of clinically isolated strains of <it>Pseudomonas aeruginosa </it>and <it>Staphylococcus aureus</it>. The anti-inflammatory activity was investigated using acute topical edema of the mouse ear induced by xylene, acute paw edema induced by agar in rats, formaldehyde arthritis in rats, vascular permeability induced by acetic acid in mice and heat- and hypotonicity-induced haemolysis of ox red blood cells (RBCs). Also evaluated were the effects on <it>in vivo </it>leukocyte migration induced by agar, phagocytic activity of macrophages on <it>Candida albicans </it>and specific cell-mediated immune responses (delayed type hypersensitivity reaction (DTHR) induced by sheep red blood cell (SRBC)). The acute toxicity and lethality (LD₅₀) in mice and phytochemical constituents of the extract were also determined.</p> <p>Results</p> <p>The extract moderately inhibited the growth of the test organisms and significantly (<it>P </it>< 0.05) inhibited (57%) topical acute edema in the mouse ear. It significantly (<it>P </it>< 0.05) suppressed the development of acute edema of the rat paw in a non-dose-related manner and was not effective in inhibiting the global edematous response to formaldehyde arthritis. It also inhibited vascular permeability induced by acetic acid in mice and the haemolysis of ox RBCs induced by heat- and hypotonicity. The extract increased total leukocyte and neutrophil counts and caused a significant (<it>P </it>< 0.05) dose-related increase in the total number of macrophages at the 800 mg/kg dose. On phagocytic activity, the extract evoked a significant (<it>P </it>< 0.05) increase in the number of macrophages with ingested <it>C. albicans </it>at 800 mg/kg dose, and significantly (<it>P </it>< 0.05) inhibited DTHR in a dose-related manner. Phytochemical tests on the extract revealed an abundant presence of alkaloids and carbohydrates while saponins, glycosides, and terpenoids occurred in trace amounts. Acute toxicity test established an oral and intraperitoneal LD₅₀greater than 5,000 mg/kg.</p> <p>Conclusion</p> <p>The effectiveness of the root of <it>A. montanus </it>in the treatment of furuncles may largely derive from mobilization of leukocytes to the site of the infection and activation of phagocytic activity as well as suppression of exacerbated immune responses by its constituents. Antimicrobial and anti-inflammatory activities are likely contributory mechanisms. Phytochemical constituents such as alkaloids and carbohydrates may be responsible for these pharmacological activities.</p

Cattle genome-wide analysis reveals genetic signatures in trypanotolerant N'Dama

Abstract Background Indigenous cattle in Africa have adapted to various local environments to acquire superior phenotypes that enhance their survival under harsh conditions. While many studies investigated the adaptation of overall African cattle, genetic characteristics of each breed have been poorly studied. Results We performed the comparative genome-wide analysis to assess evidence for subspeciation within species at the genetic level in trypanotolerant N’Dama cattle. We analysed genetic variation patterns in N’Dama from the genomes of 101 cattle breeds including 48 samples of five indigenous African cattle breeds and 53 samples of various commercial breeds. Analysis of SNP variances between cattle breeds using wMI, XP-CLR, and XP-EHH detected genes containing N’Dama-specific genetic variants and their potential associations. Functional annotation analysis revealed that these genes are associated with ossification, neurological and immune system. Particularly, the genes involved in bone formation indicate that local adaptation of N’Dama may engage in skeletal growth as well as immune systems. Conclusions Our results imply that N’Dama might have acquired distinct genotypes associated with growth and regulation of regional diseases including trypanosomiasis. Moreover, this study offers significant insights into identifying genetic signatures for natural and artificial selection of diverse African cattle breeds

Dasatinib induces rapid hematologic and cytogenetic responses in adult patients with Philadelphia chromosome positive acute lymphoblastic leukemia with resistance or intolerance to imatinib: interim results of a phase 2 study.

Patients with Philadelphia (Ph) chromosome-positive acute lymphoblastic leukemia (ALL) have a rapid disease course and a poor prognosis. Dasatinib, a novel, oral, multitargeted kinase inhibitor of BCR-ABL and SRC family kinases, has previously induced responses in patients with imatinib-resistant or -intolerant Ph-positive ALL. We present the interim results of a phase 2 study designed to further assess the efficacy, safety, and tolerability of dasatinib 140 mg in this patient population (n = 36). With a minimum follow-up of 8 months, treatment with dasatinib resulted in substantial hematologic and cytogenetic response rates. Major hematologic responses were achieved in 42% (15/36) of patients, 67% of whom remained progression-free. Complete cytogenetic responses were attained by 58% (21/36) of patients. The presence of BCR-ABL mutations conferring imatinib resistance did not preclude a response to dasatinib. Dasatinib was also tolerable, with 6% (2/36) of patients discontinuing therapy as a result of study-drug toxicity. Most adverse events (AEs) were grade 1 or 2; febrile neutropenia was the most frequent severe AE, but this and other cytopenias were manageable with dose reduction. Dasatinib represents a safe and effective treatment option and an important therapeutic advance for patients with Ph-positive ALL. This trial was registered at www.clinicaltrials.gov as #CA180015