2±0.06×104 M-1 ) in CHCl3 at room temperature.Cytochrome b5 is an essential electron transfer protein, which is ubiquitously found in living systems and involved in wide variety of biological processes. Tardigrades (also known as water bears), some of which are famous for desiccation resistance, have many proteins unique to them. Here, we report spectroscopic and structural characterization of a cytochrome b5 like protein from one of the desiccation-tolerant tardigrades, Ramazzottius varieornatus strain YOKOZUNA-1 (RvCytb5 ). A 1.4 Å resolution crystal structure revealed that RvCytb5 is a new cytochrome b5 protein specific to tardigrades.Massive craniofacial bone loss poses a clinical challenge to maxillofacial surgeons. Structural bone allografts are readily available at tissue banks but are rarely used due to a high failure rate. Previous studies showed that intermittent administration of recombinant parathyroid hormone (rPTH) enhanced integration of allografts in a murine model of calvarial bone defect. To evaluate its translational potential, the hypothesis that rPTH would enhance healing of a mandibular allograft in a clinically relevant large animal model of mandibulectomy was tested. Porcine bone allografts were implanted into a 5-cm-long continuous mandible bone defect in six adult Yucatan minipigs, which were randomized to daily intramuscular injections of rPTH (1.75 μg/kg) and placebo (n = 3). Blood tests were performed on Day 56 preoperation, Day 0 and on Day 56 postoperation. Eight weeks after the surgery, bone healing was analyzed using high-resolution X-ray imaging (Faxitron and micro computed tomography [CT]) and three-point bending biomechanical testing. The results showed a significant 2.6-fold rPTH-induced increase in bone formation (p = 0.02). Biomechanically, the yield failure properties of the healed mandibles were significantly higher in the rPTH group (yield load p less then 0.05; energy to yield p less then 0.01), and the post-yield displacement and energy were higher in the placebo group (p less then 0.05), suggesting increased mineralized integration of the allograft in the rPTH group. In contrast to similar rPTH therapy studies in dogs, no signs of hypercalcemia, hyperphosphatemia, or inflammation were detected. Taken together, we provide initial evidence that rPTH treatment enhances mandibular allograft healing in a clinically relevant large animal model.Background Eradication of persistent androgen receptor (AR) activity in castration-resistant prostate cancer may be a promising strategy to overcome castration resistance. We aimed to identify novel compounds that inhibit AR activity and could be potential therapeutic agents for prostate cancer. Methods A high-throughput screening system involving cell lines stably expressing AR protein and AR-responsive luciferase was employed for the 1260 compound library. Molecular and antitumor effects on candidate pathways that interacted with AR signaling were examined in prostate cancer cells expressing AR. Results The high-throughput screening identified various potential compounds that interfered with AR signaling through known and novel pathways. Among them, a 5-hydroxytryptamine 5A (5-HT5A) receptor antagonist suppressed AR activity through protein kinase A signaling, which was confirmed by 5-HT5A receptor knockdown. Idasanutlin Consistently, 5-HT5A receptor inhibitors showed cytotoxic effects toward prostate cancer cells. Conclusions Taken together, this study identifies 5-HT5A receptor as a promising therapeutic target for prostate cancer via its interaction with AR signaling.Background Patients who respond inadequately to plerixafor salvage during autologous peripheral blood stem cell (PBSC) collection are frequently remobilized with plerixafor to collect additional stem cells. However, in patients who fail remobilization, it is unclear whether additional mobilization efforts with plerixafor are useful. Study design and methods We retrospectively examined the PBSC collections of 15 consecutive patients with lymphoma and multiple myeloma who underwent three mobilizations with plerixafor. Results Of the 821 patients who underwent autologous stem cell collections, 15 patients were mobilized three times with plerixafor (1.8%), which enabled 11 (73.3%) patients to reach 2.0 × 106 CD34+ cells/kg or greater. Among patients who eventually collected successfully the median yields from the three collection attempts were 0.46, 0.76, and 1.54 × 106 CD34+ cells/kg, respectively. Among those who collected less than 2.0 × 106 CD34+ cells/kg cumulatively, the median yields were 0.14, 0.33, and 0.22 × 106 CD34+ cells/kg from the three collection attempts. The combined collection yields from the first two mobilization attempts were significantly lower (p = 0.003; range, 0.09-0.73 vs. 0.63-1.84; median, 0.51 vs. 1.36) in those who failed collection. Conclusions The majority (73.3%) of patients who underwent three mobilization attempts were eventually able to collect enough cells to permit autologous transplantation. Extremely low peripheral blood CD34+ count after the first dose of plerixafor and collection yields during the first two attempts were associated with a poor collection yield on the third attempt. The risks and benefits of a third mobilization should be weighed to facilitate judicious use of resources.Objective To explore the relationship between frailty, age, and detrusor overactivity (DO) in older adults presenting to an academic urology practice. Materials and methods This study uses the University of California, San Francisco Geriatric Urology Database to examine all adults ages ≥65 years who underwent urodynamic testing from December 2015 to April 2019. All subjects had a timed up and go test (TUGT) as a measure of frailty and were categorized as fast (≤10 seconds), intermediate (11-14 seconds), or slow (≥15 seconds), corresponding to not frail, pre-frail, and frail, respectively. Urodynamic studies were reviewed for the presence of DO. Univariate and multivariate logistic regression were used to examine the relationship between frailty, age, and the presence of DO. Results In total, 549 older adults underwent urodynamics during the study period, and 48.5% had a study that demonstrated DO. Individuals with DO tended to be older (18.4% vs 11.0% were ≥80 years; P = .01) and more frail (19.5% vs 13.4% with TUGT ≥5 seconds; P .