Rickettsia Phylogenomics: Unwinding the Intricacies of Obligate Intracellular Life

BACKGROUND: Completed genome sequences are rapidly increasing for Rickettsia, obligate intracellular alpha-proteobacteria responsible for various human diseases, including epidemic typhus and Rocky Mountain spotted fever. In light of phylogeny, the establishment of orthologous groups (OGs) of open reading frames (ORFs) will distinguish the core rickettsial genes and other group specific genes (class 1 OGs or C1OGs) from those distributed indiscriminately throughout the rickettsial tree (class 2 OG or C2OGs). METHODOLOGY/PRINCIPAL FINDINGS: We present 1823 representative (no gene duplications) and 259 non-representative (at least one gene duplication) rickettsial OGs. While the highly reductive (approximately 1.2 MB) Rickettsia genomes range in predicted ORFs from 872 to 1512, a core of 752 OGs was identified, depicting the essential Rickettsia genes. Unsurprisingly, this core lacks many metabolic genes, reflecting the dependence on host resources for growth and survival. Additionally, we bolster our recent reclassification of Rickettsia by identifying OGs that define the AG (ancestral group), TG (typhus group), TRG (transitional group), and SFG (spotted fever group) rickettsiae. OGs for insect-associated species, tick-associated species and species that harbor plasmids were also predicted. Through superimposition of all OGs over robust phylogeny estimation, we discern between C1OGs and C2OGs, the latter depicting genes either decaying from the conserved C1OGs or acquired laterally. Finally, scrutiny of non-representative OGs revealed high levels of split genes versus gene duplications, with both phenomena confounding gene orthology assignment. Interestingly, non-representative OGs, as well as OGs comprised of several gene families typically involved in microbial pathogenicity and/or the acquisition of virulence factors, fall predominantly within C2OG distributions. CONCLUSION/SIGNIFICANCE: Collectively, we determined the relative conservation and distribution of 14354 predicted ORFs from 10 rickettsial genomes across robust phylogeny estimation. The data, available at PATRIC (PathoSystems Resource Integration Center), provide novel information for unwinding the intricacies associated with Rickettsia pathogenesis, expanding the range of potential diagnostic, vaccine and therapeutic targets

Tissue plasminogen activator (tPA) in the management of predominantly hemorrhagic age-related macular degeneration, milligram/milliliter or microgram/milliliter?

Niels Willem Boone, Roelof Wouter Frederik van LeeuwenMaastricht University Medical Centre, Department of Clinical Pharmacy and Toxicology, Maastricht, The NetherlandsRecently our hospital pharmacy, which serves an academic hospital with an internationally well-known department of ophthalmology, received a request for the aseptic preparation of an alteplase syringe solution for subretinal administration. Looking for dose rationale, our ophthalmology doctor came up with a concentration based on an article published by Arias and colleagues in Clinical Ophthalmology in 2010

Shoulder joint range of motion in healthy adults aged 20 to 49 years

Studies of adults aged 50 years and older have shown that shoulder range of motion (ROM) is significantly less than the norms reported by the American Academy of Orthopaedic Surgeons (AAOS) and decreases with age. However, there has been little investigation of the shoulder ROM of younger adults. The aims of this study were to measure the ROM of healthy younger Australian adults aged 20 to 49 years to (1) pool with data on healthy older Australian adults aged 50 years and older from the study by McIntosh et al (2003) to provide shoulder ROM values across the adult life span; (2) compare their shoulder ROM with AAOS norms; and (3) determine the effect of background factors (age, gender, body mass index [BMI] and current activity level) on active shoulder ROM. Goniometric measurement of bilateral passive and active shoulder flexion, abduction, internal rotation and external rotation of 72 participants was compared with the AAOS norms using one-sample t-tests. The effect of the background factors on shoulder ROM was analysed using univariate General Linear Models. Significantly lower active and passive ROM (p ≤ 0.001) for all movements compared with AAOS norms was found. Active shoulder flexion, abduction and internal rotation were not significantly affected by any of the background factors. Decreased active external rotation was found for males (p = 0.020) and for older (p = 0.048) and less active (p = 0.048) participants. This study highlights the inaccuracies of the AAOS norms for younger adults aged 20 to 49 years and shows that age, gender, BMI and current activity level do not consistently have an impact on active shoulder ROM in this age group. The relevance of the AAOS norms to other joints needs investigation