Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp3.32) or V (non-canonical Asp5.42), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp5.42, gaining diamine sensitivity, and subsequently lost Asp3.32. Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs.DOI: http://dx.doi.org/10.7554/eLife.10441.001

OBJECTIVE Currently, there is no established standard regarding the ideal number of external ventricular drain (EVD) clamp trials performed before ventriculoperitoneal (VP) shunt insertion following nontraumatic subarachnoid hemorrhage (SAH). In this study, the authors aimed to evaluate this relationship. METHODS A retrospective review of all patients presenting with SAH between July 2007 and December 2016 was performed. Patients with SAH who had received an EVD within the first 24 hours of hospital admission and had undergone at least 1 clamp trial prior to EVD removal were eligible for inclusion in the study. Patient demographics, clinical presentations, SAH etiologies and grades, clamp trial data, hospital lengths of stay, and functional outcomes were recorded. RESULTS One hundred fourteen patients with nontraumatic SAH complicated by posthemorrhagic hydrocephalus were included in the study. The median patient age was 57 years (range 28-90 years), with a male/female ratio of 1:1.7. A ruptured aneurysm was the underlying etiology of SAH in 79.8% of patients. A majority of patients (69.4%) had a Hunt and Hess grade III-V on admission. The median number of clamp trials performed was 2 (range 1-6). A VP shunt was required in 40.4% of patients. In those who underwent 2 and 3 clamp trials, 60% and 38.9%, respectively, did not require subsequent VP shunt placement. CONCLUSIONS Surgical placement of a VP shunt is associated with complications. Clamp trials are routinely performed before making the decision to insert a shunt. In the present study, the authors found that a significant percentage of patients passed their second and third clamp trials without requiring subsequent shunt insertion. These data support performing multiple clamp trials prior to shunt placement.

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A five-month-old male presented with an incidentally found low-lying conus medullaris on ultrasound and subsequent MRI demonstrating its position at L4. Pre-operative examination findings included mild, global hypotonia and a coccygeal dimple without bladder or bowel abnormalities or spasticity. The patient underwent spinal cord untethering with a section of filum terminale and was discharged without complication following his procedure. Follow-up at one year revealed continued baseline hypotonia without further neurosurgical needs. This is the first reported case of tethered cord syndrome described in a patient with Pallister-Killian syndrome managed successfully with neurosurgical intervention.