Differential targeting of Gbetagamma-subunit signaling with small molecules

G protein betagamma subunits have potential as a target for therapeutic treatment of a number of diseases. We performed virtual docking of a small-molecule library to a site on Gbetagamma subunits that mediates protein interactions. We hypothesized that differential targeting of this surface could allow for selective modulation of Gbetagamma subunit functions. Several compounds bound to Gbetagamma subunits with affinities from 0.1 to 60 muM and selectively modulated functional Gbetagamma-protein-protein interactions in vitro, chemotactic peptide signaling pathways in HL-60 leukocytes, and opioid receptor-dependent analgesia in vivo. These data demonstrate an approach for modulation of G protein-coupled receptor signaling that may represent an important therapeutic strategy.     

Haplotypes of ‘<Emphasis Type="Italic">Candidatus</Emphasis> Liberibacter solanacearum’ identified in Umbeliferous crops in Spain

‘Candidatus Liberibacter solanacearum’ is a phloem-limited Gram-negative bacterium that causes serious damage to different crops of the botanical families Solanaceae and Apiaceae. Five haplotypes have been described: LsoA and LsoB are present in solanaceous crops in America and vectored by the tomato/potato psyllid Bactericera cockerelli; LsoC affects carrots from Northern and Central Europe, and is transmitted by the carrot psyllid Trioza apicalis; haplotypes LsoD and LsoE are present in Southern Europe and Morocco in carrot and celery, and are associated with the psyllid Bactericera trigonica. Thirty-four ‘Ca. L. solanacearum’ isolates were collected in six different regions of Spain from distinct Apiaceae hosts (carrot, celery, parsley and parsnip) in eight consecutive years and were analysed. Their haplotypes were determined by a sequence analysis of 16S ribosomal RNA, the 16S–26S ribosomal RNA intergenic spacer, and the 23S ribosomal RNA and rplJ and rplL genes. Both haplotypes LsoD and LsoE were found across Spain, and no host specificity appeared between these two haplotypes. This is the first report of ‘Ca. L. solanacearum’ associated with parsley and parsnip.     

Pericardial mesothelioma in a dog: long-term survival after pericardiectomy in combination with chemotherapy

A six-year-old male crossbred dog was presented with clinical signs of right-sided heart failure. Echocardiography demonstrated a pericardial effusion with cardiac tamponade, while pericardiocentesis and cytology did not reveal any evidence of malignancy. Pericardial drainage was performed twice over a period of three months to resolve haemodynamic impairment before a subtotal pericardiectomy was performed. Biopsy of parietal and visceral pericardium confirmed the diagnosis of pericardial mesothelioma. Intrathoracic cisplatin combined with intravenous doxorubicin were administered, although neutropenia, mild azotaemia and alopecia were noted as adverse reactions to these drugs. Intravenous cisplatin was repeated 45 days later after the signs of nephrotoxicity had resolved. The dog was still free of disease after 27 months. Intrathoracic chemotherapy after pericardiectomy and early diagnosis are recommended to improve prognosis, having achieved long-term survival in the present case.