Isotretinoin therapy changes the expression of antimicrobial peptides in acne vulgaris

In acne vulgaris, antimicrobial peptides (AMPs) could play a dual role; i.e., protective by acting against Propionibacterium acnes, pro-inflammatory by acting as signalling molecules. The cutaneous expression of 15 different AMPs was investigated in acne patients; furthermore, the impact of isotretinoin therapy on AMP expression was analysed in skin biopsies from 13 patients with acne vulgaris taken before, during and after a 6-month treatment cycle with isotretinoin using quantitative real-time polymerase chain reaction. Cutaneous expression of the AMPs cathelicidin, human β-defensin-2 (HBD-2), lactoferrin, lysozyme, psoriasin (S100A7), koebnerisin (S100A15), and RNase 7 was upregulated in untreated acne vulgaris, whereas α-defensin-1 (HNP-1) was downregulated compared to controls. While relative expression levels of cathelicidin, HBD-2, lactoferrin, psoriasin (S100A7), and koebnerisin (S100A15) decreased during isotretinoin treatment, only those of cathelicidin and koebnerisin returned to normal after 6 months of isotretinoin therapy. The increased expression of lysozyme and RNase 7 remained unaffected by isotretinoin treatment. The levels of granulysin, RANTES (CCL5), perforin, CXCL9, substance P, chromogranin B, and dermcidin were not regulated in untreated acne patients and isotretinoin had no effect on these AMPs. In conclusion, the expression of various AMPs is altered in acne vulgaris. Isotretinoin therapy normalizes the cutaneous production of distinct AMPs while the expression of others is still increased in healing acne. Considering the antimicrobial and pro-inflammatory role of AMPs, these molecules could serve as specific targets for acne therapy and maintenance of clinical remission.

Efficient Structure Learning of Bayesian Networks using Constraints

This paper addresses the problem of learning Bayesian network structures from data based on score functions that are decomposable. It describes properties that strongly reduce the time and memory costs of many known methods without losing global optimality guarantees. These properties are derived for different score criteria such as Minimum Description Length (or Bayesian Information Criterion), Akaike Information Criterion and Bayesian Dirichlet Criterion. Then a branch-and-bound algorithm is presented that integrates structural constraints with data in a way to guarantee global optimality. As an example, structural constraints are used to map the problem of structure learning in Dynamic Bayesian networks into a corresponding augmented Bayesian network. Finally, we show empirically the benefits of using the properties with state-of-the-art methods and with the new algorithm, which is able to handle larger data sets than before.

A fluorescence model of the C3 radical in comets

Theoretical resonance fluorescence calculations are presented of the triatomic C3 radical and are compared with observations of the C3 emission in comets Hale-Bopp and de Vico. A theoretical model of the C3 vibration-rotational structure in the A1Piu - X1Sigmag + electronic system is introduced. The model takes into account the detailed structure of the bending mode nu2 which is responsible for the emission of the 4050 Å group. A total of 1959 levels are considered, with 515 levels in the ground state. The main effort is to model high-resolution spectra of the 4050 Å emission in comets C/1995 O1 Hale-Bopp and 122P/1995 S1 de Vico. The agreement between observed and theoretical spectra is good for a value of the dipole moment derivative of dmu/dr ~ 2.5 Debye Å-1. The modeled C3 emission exhibits a pronounced Swings effect. Based on observations made with William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofisica de Canarias, and on observations made at the McDonald Observatory, which is operated by the University of Texas at Austin, USA.