Gene Ontology Consortium: going forward

The Gene Ontology (GO; http://www.geneontology.org) is a community-based bioinformatics resource that supplies information about gene product function using ontologies to represent biological knowledge. Here we describe improvements and expansions to several branches of the ontology, as well as updates that have allowed us to more efficiently disseminate the GO and capture feedback from the research community. The Gene Ontology Consortium (GOC) has expanded areas of the ontology such as cilia-related terms, cell-cycle terms and multicellular organism processes. We have also implemented new tools for generating ontology terms based on a set of logical rules making use of templates, and we have made efforts to increase our use of logical definitions. The GOC has a new and improved web site summarizing new developments and documentation, serving as a portal to GO data. Users can perform GO enrichment analysis, and search the GO for terms, annotations to gene products, and associated metadata across multiple species using the all-new AmiGO 2 browser. We encourage and welcome the input of the research community in all biological areas in our continued effort to improve the Gene Ontology

Case report: Co-existence of sarcoidosis and Takayasu arteritis

Takayasu arteritis is a rare systemic large vessel vasculitis affecting the aorta and its branches. Sarcoidosis, too, is an inflammatory disease. Both entities are granulomatous conditions with a questionable association in their etiopathogenesis. Only a few cases of their coexistence have been reported in the literature. To our knowledge, no such cases have been reported from Nepal. We report a Nepalese woman who presented with non-productive cough, progressive shortness of breath and chest tightness of 3 years duration. She had a history of recurrent bilateral granulomatous uveitis over the previous 3 years. Examination revealed clubbing of digits, absent pulses over the left radial, ulnar and brachial arteries, and a weak pulse over the right arm including the bilateral carotid arteries. Pulmonary function test showed restrictive pattern, a high-resolution computed tomography (HRCT) scan of the chest revealed findings suggestive of pulmonary sarcoidosis. A CT angiogram suggested large vessel vasculitis. Bronchoscopy with biopsy revealed granulomatous inflammation, negative for malignancy and tuberculosis. She was hence, diagnosed with co-existing Takayasu arteritis and sarcoidosis, and treated with Prednisolone 60 mg once daily with dramatic improvement over 4 days and was discharged stable on domiciliary oxygen. She is currently on azathioprine 50 mg, prednisolone 10 mg without the need for supplemental oxygen. This case report highlights the importance of a proper physical examination as a guide to the use of modern technology in making a correct diagnosis. Furthermore, in countries where tuberculosis is endemic, it should always come as the most important differential diagnosis of granulomatous inflammation

Case report: cryptococcal meningitis in an apparently immunocompetent patient in Nepal - challenges in diagnosis and treatment

A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for Cryptococcus in the CSF helped in making the diagnosis of cryptococcal meningitis in our patient who was apparently immunocompetent. Treatment with liposomal amphotericin B could not be started on time due to financial constraints. The patient had a stroke and further deteriorated. Liposomal amphotericin B is stocked by the government of Nepal for free supply to patients with visceral leishmaniasis, but the policy does not allow the drug to be dispensed for other infections. The family members of our patient acquired the drug within a few days from a government center using their political connections and following administering the treatment the patient improved. This case demonstrates the utility of considering cryptococcal meningitis as a differential diagnosis, and including tests for Cryptococcus when dealing with immunocompetent patients presenting with meningitis. It also demonstrates the effects of the sociopolitical situation on health care delivery in low- and middle-income countries (LMICs) such as Nepal

Case report: cryptococcal meningitis in an apparently immunocompetent patient in Nepal - challenges in diagnosis and treatment

A 50 year old woman from Nepal had clinical features suggestive of meningitis. Cerebrospinal fluid (CSF) analysis was normal except for the presence of cryptococcal antigen. The inclusion of test for Cryptococcus in the CSF helped in making the diagnosis of cryptococcal meningitis in our patient who was apparently immunocompetent. Treatment with liposomal amphotericin B could not be started on time due to financial constraints. The patient had a stroke and further deteriorated. Liposomal amphotericin B is stocked by the government of Nepal for free supply to patients with visceral leishmaniasis, but the policy does not allow the drug to be dispensed for other infections. The family members of our patient acquired the drug within a few days from a government center using their political connections and following administering the treatment the patient improved. This case demonstrates the utility of considering cryptococcal meningitis as a differential diagnosis, and including tests for Cryptococcus when dealing with immunocompetent patients presenting with meningitis. It also demonstrates the effects of the sociopolitical situation on health care delivery in low- and middle-income countries (LMICs) such as Nepal

Resveratrol inhibits release of soluble fms-like tyrosine kinase (sFlt-1) and soluble endoglin and improves vascular dysfunction – implications as a preeclampsia treatment

Preeclampsia is a disease of pregnancy associated with placental oxidative stress, inflammation and elevated release of anti-angiogenic factors sFlt-1 and soluble endoglin. These placental factors cause generalized maternal endothelial dysfunction. There are no treatments to halt disease progression; delivery is the only cure. Resveratrol modulates pathways involved in inflammation and oxidative stress and may offer a potential therapeutic for preeclampsia. Resveratrol reduced sFlt-1, sFlt-1 e15a and soluble endoglin secretion from primary trophoblasts and HUVECs and reduced mRNA expression of pro-inflammatory molecules NFκB, IL-6 and IL-1β in trophoblasts. IL-6, IL-1β and TNFα secretion were also significantly reduced. In HUVECs, resveratrol significantly increased mRNA of anti-oxidant enzymes HO-1, NQO1, GCLC and TXN but did not significantly alter HO-1 protein expression, whilst reducing HO-1 protein in trophoblast. Endothelial dysfunction was induced in HUVECs using TNFα, increasing expression of cell adhesion molecule VCAM1 and adhesion of peripheral blood mononuclear cells, both of which were increased further by resveratrol. In contrast, resveratrol significantly reduced TNFα-induced Endothelin-1 (a vasoconstrictor) and significantly increased the phosphorylation of endothelial nitric oxide synthase (eNOS). In summary, resveratrol decreases secretion of anti-angiogenic factors however its effects on the endothelium are mixed. Overall, it may have potential as a treatment for preeclampsia.</p