Towards Interoperability of Biomedical Ontologies

Report on Dagstuhl Seminar 07132, Schloss Dagstuhl, March 27-30 , 2007

Big Bang Nucleosynthesis with Independent Neutrino Distribution Functions

We have performed new Big Bang Nucleosynthesis calculations which employ arbitrarily-specified, time-dependent neutrino and antineutrino distribution functions for each of up to four neutrino flavors. We self-consistently couple these distributions to the thermodynamics, the expansion rate and scale factor-time/temperature relationship, as well as to all relevant weak, electromagnetic, and strong nuclear reaction processes in the early universe. With this approach, we can treat any scenario in which neutrino or antineutrino spectral distortion might arise. These scenarios might include, for example, decaying particles, active-sterile neutrino oscillations, and active-active neutrino oscillations in the presence of significant lepton numbers. Our calculations allow lepton numbers and sterile neutrinos to be constrained with observationally-determined primordial helium and deuterium abundances. We have modified a standard BBN code to perform these calculations and have made it available to the community.Comment: 9 pages, 5 figure

The durability of oral diabetic medications: Time to A1c baseline and a review of common oral medications used by the primary care provider.

Introduction:Cost of generic medications has risen more in the past few years than any other time in history. While medical insurance covers much of these costs, health care professionals can better provide medications that have the longest duration of action when compared to placebo-treated controls. This will save health care costs and improve prescribing accuracy. Methods:Papers in PubMed were identified with keywords placebo. The study must be at least 2 years in length to evaluate the change in A1c over time. The primary endpoint was time to A1c neutrality (return of A1c to baseline at a maximum dose of single oral agent). A medication would be considered at neutrality if the 95% CI crossed baseline. Time to neutrality was averaged for each medication within the class and each summarized for class effect. Results:Effective therapy for the DPP-4 and sulfonylurea classes of medications are 3-4 years as compared to a 5-year time to A1c neutrality for metformin usage. In comparison, the projected time to A1c neutrality was approximately 6-8 years for rosiglitazone and pioglitazone. While only a few studies have been published in the SGLT-2 class of medication, the time to A1c neutrality was also 6-8 years with Canagliflozin and full dosage of Empagliflozin. Conclusion:Metformin appears to have a 5-year duration of effect before the A1c returns to baseline. The sulfonylureas and DPP-4 inhibitors class of medications have one of the shortest durability which ranges between 3.3 to 4.4 years. In contrast, the SGLT-2 class of medication and the TZD class of medications has a projected time to A1c neutrality from 6-8 years. Diabetic duration of therapy as compared to placebo should be listed with those medications tested so the provider can choose wisely

Nitric Oxide Mediates Biofilm Formation and Symbiosis in Silicibacter sp. Strain TrichCH4B.

UnlabelledNitric oxide (NO) plays an important signaling role in all domains of life. Many bacteria contain a heme-nitric oxide/oxygen binding (H-NOX) protein that selectively binds NO. These H-NOX proteins often act as sensors that regulate histidine kinase (HK) activity, forming part of a bacterial two-component signaling system that also involves one or more response regulators. In several organisms, NO binding to the H-NOX protein governs bacterial biofilm formation; however, the source of NO exposure for these bacteria is unknown. In mammals, NO is generated by the enzyme nitric oxide synthase (NOS) and signals through binding the H-NOX domain of soluble guanylate cyclase. Recently, several bacterial NOS proteins have also been reported, but the corresponding bacteria do not also encode an H-NOX protein. Here, we report the first characterization of a bacterium that encodes both a NOS and H-NOX, thus resembling the mammalian system capable of both synthesizing and sensing NO. We characterized the NO signaling pathway of the marine alphaproteobacterium Silicibacter sp. strain TrichCH4B, determining that the NOS is activated by an algal symbiont, Trichodesmium erythraeum. NO signaling through a histidine kinase-response regulator two-component signaling pathway results in increased concentrations of cyclic diguanosine monophosphate, a key bacterial second messenger molecule that controls cellular adhesion and biofilm formation. Silicibacter sp. TrichCH4B biofilm formation, activated by T. erythraeum, may be an important mechanism for symbiosis between the two organisms, revealing that NO plays a previously unknown key role in bacterial communication and symbiosis.ImportanceBacterial nitric oxide (NO) signaling via heme-nitric oxide/oxygen binding (H-NOX) proteins regulates biofilm formation, playing an important role in protecting bacteria from oxidative stress and other environmental stresses. Biofilms are also an important part of symbiosis, allowing the organism to remain in a nutrient-rich environment. In this study, we show that in Silicibacter sp. strain TrichCH4B, NO mediates symbiosis with the alga Trichodesmium erythraeum, a major marine diazotroph. In addition, Silicibacter sp. TrichCH4B is the first characterized bacteria to harbor both the NOS and H-NOX proteins, making it uniquely capable of both synthesizing and sensing NO, analogous to mammalian NO signaling. Our study expands current understanding of the role of NO in bacterial signaling, providing a novel role for NO in bacterial communication and symbiosis