Challenges in the Diagnosis and Management of Spinal Tuberculosis: Case Series.

Though uncommon in developed countries, spinal tuberculosis must still be considered in patients with a suspicious clinical history, to avoid delays in treatment. This case series highlights the special considerations that need to be taken into account while tackling the diagnostic and therapeutic challenges associated with this disease. We present two interesting cases of spinal tuberculosis. The first case was a 26-year-old female who presented with chronic back pain and an initial misdiagnosis of ankylosing spondylitis. The second case was a 26-year-old male with new lower extremity weakness, numbness, and urinary retention. Both cases had clear indications for surgery, however, the first case was treated with medical management upon patient request. The patient was managed non-surgically and improved clinically though she may need surgery in the future. The second case was treated with emergency surgery and the patient regained full neurologic function at follow-up. These cases demonstrate the importance of considering spinal tuberculosis in the differential diagnosis of high-risk patients as well as individualizing treatment strategies for each patient.

Late steps in cytoplasmic maturation of assembly-competent axonemal outer arm dynein in Chlamydomonas require interaction of ODA5 and ODA10 in a complex.

Axonemal dyneins are multisubunit enzymes that must be preassembled in the cytoplasm, transported into cilia by intraflagellar transport, and bound to specific sites on doublet microtubules, where their activity facilitates microtubule sliding-based motility. Outer dynein arms (ODAs) require assembly factors to assist their preassembly, transport, and attachment to cargo (specific doublet A-tubule sites). In Chlamydomonas, three assembly factors--ODA5, ODA8, and ODA10--show genetic interactions and have been proposed to interact in a complex, but we recently showed that flagellar ODA8 does not copurify with ODA5 or ODA10. Here we show that ODA5 and ODA10 depend on each other for stability and coexist in a complex in both cytoplasmic and flagellar extracts. Immunofluorescence and immuno-electron microscopy reveal that ODA10 in flagella localizes strictly to a proximal region of doublet number 1, which completely lacks ODAs in Chlamydomonas. Studies of the in vitro binding of ODAs to axonemal doublets reveal a role for the ODA5/ODA10 assembly complex in cytoplasmic maturation of ODAs into a form that can bind to doublet microtubules.

Chlamydomonas ODA10 is a conserved axonemal protein that plays a unique role in outer dynein arm assembly.

Assembly of outer dynein arms (ODAs) requires multiple steps and involves multiple proteins in addition to dynein subunits. The Chlamydomonas ODA10, ODA5, and ODA8 loci genetically interact and are hypothesized to function as an axonemal accessory complex, but only ODA5p was previously characterized. We positionally cloned ODA10 and identified the gene by rescuing an oda10 mutant with a hemagglutinin-tagged cDNA. ODA10 sequence predicts a conserved coiled-coil protein homologous to mouse ccdc151. ODA10p is present in cytoplasm and flagella, remains axonemal after detergent treatment, and is extracted with 0.6 M NaCl. Both outer arm dynein and ODA10p rebound to the axonemes when desalted extracts are mixed with oda10-mutant axonemes. Sucrose gradient separation of these extracts shows that ODA10p sediments near the top of the gradient, not with 23S outer dynein arm proteins. Unexpectedly, dynein and ODA10p fractions are able to bind individually to oda10 axonemes. ODA10p is present on oda8-mutant flagella at wild-type levels. However, ODA10p does not assemble into oda5 flagella and is absent from oda5 cytoplasm, suggesting a necessity of ODA5p for stability of ODA10p in vivo. The results suggest that ODA10p does not function as a part of a traditionally defined docking complex.