Reduction of Paraoxonase Expression Followed by Inactivation across Independent Semiaquatic Mammals Suggests Stepwise Path to Pseudogenization.

Convergent adaptation to the same environment by multiple lineages frequently involves rapid evolutionary change at the same genes, implicating these genes as important for environmental adaptation. Such adaptive molecular changes may yield either change or loss of protein function; loss of function can eliminate newly deleterious proteins or reduce energy necessary for protein production. We previously found a striking case of recurrent pseudogenization of the Paraoxonase 1 (Pon1) gene among aquatic mammal lineages-Pon1 became a pseudogene with genetic lesions, such as stop codons and frameshifts, at least four times independently in aquatic and semiaquatic mammals. Here, we assess the landscape and pace of pseudogenization by studying Pon1 sequences, expression levels, and enzymatic activity across four aquatic and semiaquatic mammal lineages: pinnipeds, cetaceans, otters, and beavers. We observe in beavers and pinnipeds an unexpected reduction in expression of Pon3, a paralog with similar expression patterns but different substrate preferences. Ultimately, in all lineages with aquatic/semiaquatic members, we find that preceding any coding-level pseudogenization events in Pon1, there is a drastic decrease in expression, followed by relaxed selection, thus allowing accumulation of disrupting mutations. The recurrent loss of Pon1 function in aquatic/semiaquatic lineages is consistent with a benefit to Pon1 functional loss in aquatic environments. Accordingly, we examine diving and dietary traits across pinniped species as potential driving forces of Pon1 functional loss. We find that loss is best associated with diving activity and likely results from changes in selective pressures associated with hypoxia and hypoxia-induced inflammation.

cytoNet: Spatiotemporal network analysis of cell communities.

We introduce cytoNet, a cloud-based tool to characterize cell populations from microscopy images. cytoNet quantifies spatial topology and functional relationships in cell communities using principles of network science. Capturing multicellular dynamics through graph features, cytoNet also evaluates the effect of cell-cell interactions on individual cell phenotypes. We demonstrate cytoNet's capabilities in four case studies: 1) characterizing the temporal dynamics of neural progenitor cell communities during neural differentiation, 2) identifying communities of pain-sensing neurons in vivo, 3) capturing the effect of cell community on endothelial cell morphology, and 4) investigating the effect of laminin α4 on perivascular niches in adipose tissue. The analytical framework introduced here can be used to study the dynamics of complex cell communities in a quantitative manner, leading to a deeper understanding of environmental effects on cellular behavior. The versatile, cloud-based format of cytoNet makes the image analysis framework accessible to researchers across domains.

[Etiology of pneumonia in chilean HIV-infected adult patients]. / Etiología de la neumonía en pacientes chilenos infectados por el virus de la inmunodeficiencia humana.

OBJECTIVES: To establish the etiology of pneumonia and to compare the yield of diagnostic techniques for diagnosis of Pneumocystis jiroveci and Mycobacterium tuberculosis infections in HIV-1-infected patients. PATIENTS AND METHODS: Subjects underwent sputum induction and bronchoalveolar lavage (BAL). Gram, Ziehl-Neelsen, silver stain (SS) and immunofluorescense staining (IF) for P. jiroveci, fluorescent stain for mycobacteria, PCR for P. jiroveci and M. tuberculosis, aerobic, fungal and mycobacterial cultures, respiratory viruses and CMV cultures were performed on the sputum and BAL. IgM for Mycoplasma pneumoniae and Chlamydophyla pneumoniae, and Legionella pneumophila urinary antigen were also obtained. RESULTS: Sixty patients were included. An etiologic diagnosis was made in 97%. Pneumocystis jiroveci was the most frequent etiology (58%) followed by Streptococcus pneumoniae (12%), and Mycobacterium avium complex (12%). Mycobacterium tuberculosis was found in 5%. CONCLUSIONS: The comparison of diagnostic methods for P. jiroveci showed a higher sensitivity of IF and SS in BAL than in sputum, however PCR was equally sensitive in both samples. With this approach a precise etiologic diagnosis was reached in the great majority of patients. The most common etiology was P. jiroveci. IF in BAL remains the gold standard for diagnosis of P. jiroveci pneumonia.