7 research outputs found
A Trigger Enzyme in Mycoplasma pneumoniae: Impact of the Glycerophosphodiesterase GlpQ on Virulence and Gene Expression
Mycoplasma pneumoniae is a causative agent of atypical pneumonia. The formation of hydrogen peroxide, a product of glycerol metabolism, is essential for host cell cytotoxicity. Phosphatidylcholine is the major carbon source available on lung epithelia, and its utilization requires the cleavage of deacylated phospholipids to glycerol-3-phosphate and choline. M. pneumoniae possesses two potential glycerophosphodiesterases, MPN420 (GlpQ) and MPN566. In this work, the function of these proteins was analyzed by biochemical, genetic, and physiological studies. The results indicate that only GlpQ is an active glycerophosphodiesterase. MPN566 has no enzymatic activity as glycerophosphodiesterase and the inactivation of the gene did not result in any detectable phenotype. Inactivation of the glpQ gene resulted in reduced growth in medium with glucose as the carbon source, in loss of hydrogen peroxide production when phosphatidylcholine was present, and in a complete loss of cytotoxicity towards HeLa cells. All these phenotypes were reverted upon complementation of the mutant. Moreover, the glpQ mutant strain exhibited a reduced gliding velocity. A comparison of the proteomes of the wild type strain and the glpQ mutant revealed that this enzyme is also implicated in the control of gene expression. Several proteins were present in higher or lower amounts in the mutant. This apparent regulation by GlpQ is exerted at the level of transcription as determined by mRNA slot blot analyses. All genes subject to GlpQ-dependent control have a conserved potential cis-acting element upstream of the coding region. This element overlaps the promoter in the case of the genes that are repressed in a GlpQ-dependent manner and it is located upstream of the promoter for GlpQ-activated genes. We may suggest that GlpQ acts as a trigger enzyme that measures the availability of its product glycerol-3-phosphate and uses this information to differentially control gene expression
Crystallographic ab initio protein structure solution below atomic resolution
4 pages, 1 figure, 1 table.-- PMID: 19684596 [PubMed].-- Printed version published Sep 2009.Supporting information (Suppl. figs S1-S2, suppl. table S1 and suppl. results) available at: http://www.nature.com/nmeth/journal/v6/n9/suppinfo/nmeth.1365_S1.htmlMore information on Arcimboldo available at: http://chango.ibmb.csic.es/ARCIMBOLDO/Ab initio macromolecular phasing has been so far limited to small proteins diffracting at atomic resolution (beyond 1.2 Ã…) unless heavy atoms are present. We describe a general ab initio phasing method for 2 Ã… data, based on combination of localizing model fragments such as small á-helices with Phaser and density modification with SHELXE. We implemented this approach in the program Arcimboldo to solve a 222-amino-acid structure at 1.95 Ã….This work was supported by the European Union Integrated Project Biocrystallography (X) on a highly integrated technology platform for European Structural Genomics, the Spanish Ministry of Science and Innovation (grant BIO2006-06653), Fonds der Chemischen Industrie, Deutsche Forschungsgemeinschaft (DFG-IRTG1422) and the Max Planck Society. D.D.R. thanks Consejo Superior de Investigaciones CientÃficas for grant I3PMas_08_00057 for the Master in Crystallography and Crystallization, Universidad Internacional Menéndez Pelayo. We are also grateful to Institut d’EstadÃstica de Catalunya for its contribution to grid computing.Peer reviewe
A Review of the Diagnosis and Management of Hoarding Disorder
Hoarding disorder (HD) is a severe psychiatric and public health problem characterized by extreme challenges with discarding possessions and severe acquisition resulting in excessive clutter that impairs daily functioning and may cause substantial health and safety risks. Over the past 20Â years, research on HD has grown substantially and lead to its recent designation in the DSM-5 as a discrete disorder. The key features of the cognitive behavioral etiological model of hoarding include core vulnerabilities, information processing deficits, cognitions and meaning of possessions, and emotionally driven reinforcement patterns. This model has served as the theoretical foundation for efficacious, specialized cognitive behavioral treatment (CBT) for hoarding and validated hoarding assessment measures. The individual manualized CBT treatment has been adapted for delivery through various modalities (e.g., group, web-based, self-help), populations (e.g., geriatric), and providers (e.g., clinicians, peer support, case managers). While CBT is associated with significant reductions in hoarding severity, clinical levels of hoarding symptoms persist for greater than half of treatment completers; thus, more efficacious treatments need to be developed. Further research is necessary to elucidate components of the CBT model and their interaction, in order to inform treatment targets. Although research on pharmacological treatments for HD is in the nascent stages and extant results are somewhat mixed, future studies may assess medication as a standalone treatment or combined with CBT. Family-focused hoarding interventions may also be important given that persons with hoarding behaviors may have limited insight and motivation and its negative effects on the family. Current data indicate a cost-effective and coordinated response that combines community-based and individualized interventions for hoarding may be optimal in order to (1) reach the broadest group of clients with hoarding (e.g., beyond those who voluntarily seek treatment), (2) maximize incentives and motivation through housing, health services, and safety laws, (3) enhance communication and coordination between diverse teams of providers, (4) provide sustainable comprehensive services in a stepped care approach, and (5) reduce stigma