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S100A12 Suppresses Pro-inflammatory, but Not Pro-Thrombotic Functions of Serum Amyloid A
Yuen Ming Chung, Jesse Goyette, Nicodemus Tedla, Kenneth Hsu, Carolyn L. Geczy
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0062372
Abstract: S100A12 is elevated in the circulation in patients with chronic inflammatory diseases and recent studies indicate pleiotropic functions. Serum amyloid A induces monocyte cytokines and tissue factor. S100A12 did not stimulate IL-6, IL-8, IL-1β or TNF-α production by human peripheral blood mononuclear cells but low amounts consistently reduced cytokine mRNA and protein levels induced by serum amyloid A, by ~49% and ~46%, respectively. However, S100A12 did not affect serum amyloid A-induced monocyte tissue factor. In marked contrast, LPS-induced cytokines or tissue factor were not suppressed by S100A12. S100A12 did not alter cytokine mRNA stability or the cytokine secretory pathway. S100A12 and serum amyloid A did not appear to form complexes and although they may have common receptors, suppression was unlikely via receptor competition. Serum amyloid A induces cytokines via activation of NF-κB and the MAPK pathways. S100A12 reduced serum amyloid A-, but not LPS-induced ERK1/2 phosphorylation to baseline. It did not affect JNK or p38 phosphorylation or the NF-κB pathway. Reduction in ERK1/2 phosphorylation by S100A12 was unlikely due to changes in intracellular reactive oxygen species, Ca2+ flux or to recruitment of phosphatases. We suggest that S100A12 may modulate sterile inflammation by blunting pro-inflammatory properties of lipid-poor serum amyloid A deposited in chronic lesions where both proteins are elevated as a consequence of macrophage activation.
LILRA2 Selectively Modulates LPS-Mediated Cytokine Production and Inhibits Phagocytosis by Monocytes
Hao K. Lu,Ainslie Mitchell,Yasumi Endoh,Taline Hampartzoumian,Owen Huynh,Luis Borges,Carolyn Geczy,Katherine Bryant,Nicodemus Tedla
PLOS ONE , 2012, DOI: 10.1371/journal.pone.0033478
Abstract: The activating immunoglobulin-like receptor, subfamily A, member 2 (LILRA2) is primarily expressed on the surface of cells of the innate immunity including monocytes, macrophages, neutrophils, basophils and eosinophils but not on lymphocytes and NK cells. LILRA2 cross-linking on monocytes induces pro-inflammatory cytokines while inhibiting dendritic cell differentiation and antigen presentation. A similar activating receptor, LILRA4, has been shown to modulate functions of TLR7/9 in dendritic cells. These suggest a selective immune regulatory role for LILRAs during innate immune responses. However, whether LILRA2 has functions distinct from other receptors of the innate immunity including Toll-like receptor (TLR) 4 and FcγRI remains unknown. Moreover, the effects of LILRA2 on TLR4 and FcγRI-mediated monocyte functions are not elucidated. Here, we show activation of monocytes via LILRA2 cross-linking selectively increased GM-CSF production but failed to induce IL-12 and MCP-1 production that were strongly up-regulated by LPS, suggesting functions distinct from TLR4. Interestingly, LILRA2 cross-linking on monocytes induced similar amounts of IL-6, IL-8, G-CSF and MIP-1α but lower levels of TNFα, IL-1β, IL-10 and IFNγ compared to those stimulated with LPS. Furthermore, cross-linking of LILRA2 on monocytes significantly decreased phagocytosis of IgG-coated micro-beads and serum opsonized Escherichia coli but had limited effect on phagocytosis of non-opsonized bacteria. Simultaneous co-stimulation of monocytes through LILRA2 and LPS or sequential activation of monocytes through LILRA2 followed by LPS led lower levels of TNFα, IL-1β and IL-12 production compared to LPS alone, but had additive effect on levels of IL-10 and IFNγ but not on IL-6. Interestingly, LILRA2 cross-linking on monocytes caused significant inhibition of TLR4 mRNA and protein, suggesting LILRA2-mediated suppression of LPS responses might be partly via regulation of this receptor. Taken together, we provide evidence that LILRA2-mediated activation of monocytes is significantly different to LPS and that LILRA2 selectively modulates LPS-mediated monocyte activation and FcγRI-dependent phagocytosis.
Anti-Inflammatory and Anti-Remodelling Effects of ISU201, a Modified Form of the Extracellular Domain of Human BST2, in Experimental Models of Asthma: Association with Inhibition of Histone Acetylation
Cristan Herbert, Alexander M. Shadie, Melissa M. Bunting, Nicodemus Tedla, Linda Garthwaite, Araluen Freeman, Hyouna Yoo, Sang-Ho Park, Rakesh K. Kumar
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0090436
Abstract: There are few alternatives to glucocorticosteroids for treatment of asthma. We assessed the activity of a novel protein drug designated ISU201, the extracellular domain of the human cell surface protein BST2, stabilised by fusion with the Fc region of IgG, in mouse models of mild chronic asthma and an acute exacerbation of asthma. The ability of ISU201 to suppress airway inflammation and remodelling was compared with that of dexamethasone. Female BALB/c mice were systemically sensitised with ovalbumin, then received controlled low-level challenge with aerosolised ovalbumin for 6 weeks, which induced lesions of mild chronic asthma, and were treated with drugs during the final 2 weeks. Alternatively, sensitised mice received 4 weeks of chronic low-level challenge and were treated 24 and 2 hours before a final single moderate-level challenge, which triggered acute airway inflammation simulating an asthmatic exacerbation. Inflammation and remodelling were quantified, as was the expression of pro-inflammatory cytokines in bronchoalveolar lavage fluid and tissues. To identify cellular targets of ISU201, we assessed the effects of the drug on activated lymphocytes, macrophages and airway epithelial cells. In the model of mild chronic asthma, ISU201 was as effective as dexamethasone in suppressing airway inflammation and most changes of remodelling. In the model of an allergen-induced acute exacerbation of chronic asthma, ISU201 was also an effective anti-inflammatory agent, although it was less active than dexamethasone. The drug acted on multiple cellular targets, suppressing production of pro-inflammatory cytokines by lymphocytes and macrophages. ISU201 significantly reduced acetylation of histone H4 in airway epithelial cells, suggesting at least one potential mechanism of action. We conclude that in these models of asthma, ISU201 is a broad-spectrum inhibitor of both airway inflammation and remodelling. Thus, unlike drugs which target specific mediators, it could potentially be an alternative or an adjunct to glucocorticoids for the treatment of asthma.
Occurrence of European Rhinoceros Beetle, Oryctes nasicornis (L.) (Coleoptera: Scarabaeidae), in the Southern Highlands of Tanzania  [PDF]
Nicodemus D. Matojo
Advances in Entomology (AE) , 2018, DOI: 10.4236/ae.2018.61002
Abstract: The European rhinoceros beetle, Oryctes nasicornis (L.), is a large flying beetle in the subfamily Dynastinae of family Scarabaeidae and order Coleoptera. It is well-known to be a Palaearctic species, inhabiting Europe and Asia up to North Africa, with no reported material from the Sub-Saharan African region including Tanzania. The present work reports an occurrence of O. nasicornis in Tanzania specifically in Iringa region in the Southern Highlands zone of the country. The report is accompanied by description of the key morphological characters of the insect validating its diagnosis. The findings facilitate a basis for intervention of the existing records about O. nasicornis, including its biogeographical affiliation and the related undertakings. It is most likely that the species also ranges in other localities in Tanzania and the Sub-Saharan Africa region in general because of the existing proximity and interactions.
amLite: Amharic Transliteration Using Key Map Dictionary
Tadele Tedla
Computer Science , 2015,
Abstract: amLite is a framework developed to map ASCII transliterated Amharic texts back to the original Amharic letter texts. The aim of such a framework is to make existing Amharic linguistic data consistent and interoperable among researchers. For achieving the objective, a key map dictionary is constructed using the possible ASCII combinations actively in use for transliterating Amharic letters; and a mapping of the combinations to the corresponding Amharic letters is done. The mapping is then used to replace the Amharic linguistic text back to form the original Amharic letters text. The framework indicated 97.7, 99.7 and 98.4 percentage accuracy on converting the three sample random test data. It is; however, possible to improve the accuracy of the framework by adding an exception to the implementation of the algorithm, or by preprocessing the input text prior to conversion. This paper outlined the rationales behind the need for developing the framework and the processes undertaken in the development.
New answers to age-old questions: Using proteomics to elucidate the mechanisms of ageing
Nicodemus Oey
University of Toronto Journal of Undergraduate Life Sciences , 2007,
Patients satisfaction with laboratory services at antiretroviral therapy clinics in public hospitals, Addis Ababa, Ethiopia
Tedla Mindaye, Bineyam Taye
BMC Research Notes , 2012, DOI: 10.1186/1756-0500-5-184
Abstract: Hospital based, descriptive cross sectional study was conducted from October to November 2010 among clients attending in nine public hospitals ART clinics in Addis Ababa Ethiopia. Patients’ satisfaction towards laboratory services was assessed using exit interview structured questionnaire. Data were coded and entered using EPI info 2002 (Centers for Disease Control and Prevention Atlanta, GA) and analyzed using SPSS version 15 software (SPSS INC, Chicago, IL, USA).A total of 406 clients were involved in the study. Of these 255(62.8%) were females. The overall satisfaction rate for ART monitoring laboratory services was (85.5%). Patients were satisfied with measures taken by health care providers to keep confidentiality and ability of the person drawing blood to answer question (98.3% and 96.3% respectively). Moreover, the finding of this study revealed, statistical significant associations between the overall patients’ satisfaction with waiting time to get blood drawing service, availability of ordered laboratory tests and waiting time to get laboratory result with (p?<?0.05). Patients receiving blood drawing service less than 30 minute were 7.59 times (95% CI AOR: 3.92–14.70) to be more satisfied with ART monitoring laboratory services compared to those who underwent for more than 30 minutes.Overall, the satisfaction survey showed, most respondents were satisfied with ART monitoring laboratory services. However, factors such as improving accessibility and availability of latrines should be taken into consideration in order to improve the overall satisfaction.Patient satisfaction is the patient’s perception of care received compared with the care expected [1]. Evaluating to what extent patients are satisfied with health services is clinically relevant, as satisfied patients are more likely to comply with treatment [2], take an active role in their own care [3], continue using medical care services and stay within a health provider (where there are some choices) and
The Importance of Self-Advocacy Skills for Students with Disabilities in Higher Education for a Full Inclusion and a Glimpse of Ethiopian Case: A Review of Related Literature  [PDF]
Tadesse Abera Tedla
Open Access Library Journal (OALib Journal) , 2017, DOI: 10.4236/oalib.1103174
The transition from high schools to higher education institutions can be especially difficult for students with disabilities as the impetus for securing necessary accommodations falls on students themselves rather than on parents or on the institution as it did in high schools. Students with disabilities are still facing issues in both their transition to higher education institutions and their retention to complete a degree or certificate. Educators and researchers suggest that self-advocacy skills would address the issue. A self-advocacy skill is an evidence-based predictor in secondary transition, having an impact on improved post-school outcomes in education and employment. Coming to Ethiopia, over the last few years, higher educational institutions in Ethiopia increased from 11 to 32. Universities and enrollment rate also reached to 100,000 per annum. However, the number of students with disabilities in the universities is still low. Those who joined the universities have experienced challenges of different types ranging from academic to social. Ethiopian institutions do not have any explicit policy for students with disabilities. Similarly, the available provision for students with disabilities, if any, is negligible. For example, in the university where I work in students with physical impairments are facing lack of educational materials, non-inclusive environment (inaccessibility of library, dormitory, toilet rooms, classrooms, roads, and the like) and lack of awareness by the university community. Hence, although making higher institutions to be inclusive for students with disabilities is the responsibility of higher education communities and other stakeholders, students with disabilities are also expected to play a role (by using self-advocacy skills) to get appropriate services and supports to complete their education with better academic and psycho-social achievement that enable them to be competitive in the world of job and social integration, which is the aim of this review literature.
Accounting Systems for Records Keeping Practices for Small Enterprise Development in Makueni County, Kenya  [PDF]
Nicodemus Muteti, Mary Namusonge, David Nzomo
Open Journal of Accounting (OJAcct) , 2018, DOI: 10.4236/ojacct.2018.73012
Abstract: Small enterprise development strategy is used by governments worldwide for economic development, wealth creation and poverty reduction. The government of Kenya vision 2030 of being a medium income economy is anchored on an ambitious economic development blueprint through economic, social and political pillars. While small enterprises are taunted as part of the catalysts for development, by their nature small enterprises face a myriad of challenges in the collection of financial information through accounting system which is used in business decision making. The study considered the challenges faced by the enterprises in record keeping, the type of accounting systems they use and the role of accounting systems in enterprise development in Makueni County, Kenya. Data for the study was collected from 250 small enterprises through semi-structured questionnaires analysed using descriptive and inferential statistics. Small enterprises prefer maintaining manual records of accounting systems for recording purchases, sales and expenses. The challenges faced were lack of competent clerical staff, time constraints and lack of knowledge on record keeping. A significant linear relationship is evident between accounting systems and enterprise development in Makueni County of Kenya. There is need for the government and other stake holders to intervene in capacity building of small enterprises on accounting practices as a pillar to the development and sustainability of small enterprises in Kenya.
catmap: Case-control And TDT Meta-Analysis Package
Kristin K Nicodemus
BMC Bioinformatics , 2008, DOI: 10.1186/1471-2105-9-130
Abstract: I introduce the package catmap for the R statistical computing environment that implements fixed- and random-effects pooled estimates for case-control and transmission disequilibrium methods, allowing for the use of genetic association data across study types. In addition, catmap may be used to create forest and funnel plots and to perform sensitivity analysis and cumulative meta-analysis. catmap is available from the Comprehensive R Archive Network http://www.r-project.org webcite.catmap allows researchers to synthesize data to assess evidence for association in studies of genetic polymorphisms, facilitating the use of pooled data analyses which may increase power to detect moderate genetic associations.Two study designs are commonly employed in genetic association studies: a case-control and a family-based approach. The case-control design compares frequencies of alleles carried among cases with a disease and among controls that are free of disease. The family-based design compares the frequency of alleles transmitted to an affected offspring by their parents with alleles carried by the parents but not passed to the offspring; this type of statistical analysis is often called a transmission disequilibrium test (TDT). Complex diseases are likely to be under the influence of several genetic risk factors; therefore, the contribution of a single gene to risk of disease is expected to be modest. Meta-analysis allows for the pooling of independent studies that examine similar hypotheses; for example, that a particular allele at a SNP is associated with disease status, and thus may improve power to detect moderate effect sizes. Although a few methods have been developed to combine family-based data with data from unrelated controls and/or unrelated cases obtained by the same study [1-10], most of these methods are not specifically designed to pool results from multiple independent studies and thus do not have a built-in test for heterogeneity of effect, which may be used
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