Nematostella vectensis exemplifies the exceptional expansion and diversity of opsins in the eyeless Hexacorallia.

BACKGROUND: Opsins are the primary proteins responsible for light detection in animals. Cnidarians (jellyfish, sea anemones, corals) have diverse visual systems that have evolved in parallel with bilaterians (squid, flies, fish) for hundreds of millions of years. Medusozoans (e.g., jellyfish, hydroids) have evolved eyes multiple times, each time independently incorporating distinct opsin orthologs. Anthozoans (e.g., corals, sea anemones,) have diverse light-mediated behaviors and, despite being eyeless, exhibit more extensive opsin duplications than medusozoans. To better understand the evolution of photosensitivity in animals without eyes, we increased anthozoan representation in the phylogeny of animal opsins and investigated the large but poorly characterized opsin family in the sea anemone Nematostella vectensis. RESULTS: We analyzed genomic and transcriptomic data from 16 species of cnidarians to generate a large opsin phylogeny (708 sequences) with the largest sampling of anthozoan sequences to date. We identified 29 opsins from N. vectensis (NvOpsins) with high confidence, using transcriptomic and genomic datasets. We found that lineage-specific opsin duplications are common across Cnidaria, with anthozoan lineages exhibiting among the highest numbers of opsins in animals. To establish putative photosensory function of NvOpsins, we identified canonically conserved protein domains and amino acid sequences essential for opsin function in other animal species. We show high sequence diversity among NvOpsins at sites important for photoreception and transduction, suggesting potentially diverse functions. We further examined the spatiotemporal expression of NvOpsins and found both dynamic expression of opsins during embryonic development and sexually dimorphic opsin expression in adults. CONCLUSIONS: These data show that lineage-specific duplication and divergence has led to expansive diversity of opsins in eyeless cnidarians, suggesting opsins from these animals may exhibit novel biochemical functions. The variable expression patterns of opsins in N. vectensis suggest opsin gene duplications allowed for a radiation of unique sensory cell types with tissue- and stage-specific functions. This diffuse network of distinct sensory cell types could be an adaptive solution for varied sensory tasks experienced in distinct life history stages in Anthozoans.

A selective inhibitor of the sperm-specific potassium channel SLO3 impairs human sperm function.

To fertilize an oocyte, the membrane potential of both mouse and human sperm must hyperpolarize (become more negative inside). Determining the molecular mechanisms underlying this hyperpolarization is vital for developing new contraceptive methods and detecting causes of idiopathic male infertility. In mouse sperm, hyperpolarization is caused by activation of the sperm-specific potassium (K+) channel SLO3 [C. M. Santi et al., FEBS Lett. 584, 1041-1046 (2010)]. In human sperm, it has long been unclear whether hyperpolarization depends on SLO3 or the ubiquitous K+ channel SLO1 [N. Mannowetz, N. M. Naidoo, S. A. S. Choo, J. F. Smith, P. V. Lishko, Elife 2, e01009 (2013), C. Brenker et al., Elife 3, e01438 (2014), and S. A. Mansell, S. J. Publicover, C. L. R. Barratt, S. M. Wilson, Mol. Hum. Reprod. 20, 392-408 (2014)]. In this work, we identified the first selective inhibitor for human SLO3-VU0546110-and showed that it completely blocked heterologous SLO3 currents and endogenous K+ currents in human sperm. This compound also prevented sperm from hyperpolarizing and undergoing hyperactivated motility and induced acrosome reaction, which are necessary to fertilize an egg. We conclude that SLO3 is the sole K+ channel responsible for hyperpolarization and significantly contributes to the fertilizing ability of human sperm. Moreover, SLO3 is a good candidate for contraceptive development, and mutation of this gene is a possible cause of idiopathic male infertility.

Outcomes of fracture-related infections - do organism, depth of involvement, and temporality count?

Purpose: To determine mortality and outcomes of patients diagnosed with fracture-related infections (FRIs).Methods: FRI patients treated at a trauma centre between 2001 and 2020 were analysed. The primary outcome was 1-year mortality; mortality associations with FRI organism, depth of involvement, and temporality were investigated with multivariable survival analysis. Healthcare-associated and serological outcomes were reported as secondary outcomes. Results: 311 FRIs with mean age of 67.0 and median Charlson comorbidity index of 0 were analysed. Methicillin-sensitive Staphylococcus aureus (MSSA) (29.9%) was the most frequently implicated organism. The majority of FRIs were deep infections (62.7%). FRIs were diagnosed at a median of 40 (IQR 15-200) days post index surgery. The mean follow-up was 5.9 years. One-year mortality amounted to 17.7%. MSSA FRIs were associated with better survival (adj HR 0.34, 95%CI 0.15-0.76, p = 0.008). There was no difference in survivorship between deep or superficial FRI (adj HR 0.86, 95%CI 0.62-1.19, p = 0.353) or in relation to onset time (adj HR 1.0, 95%CI 0.99-1.00, p = 0.943). Implant removal or debridement alone was performed in 61.7% and 17% respectively. Antibiotics was prescribed for 53 (IQR 23-110) days, and patients were hospitalised for 39 (IQR 19-78) days. CRP and ESR normalised in 70.3% (median 46 days) and 53.8% (median 86 days) patients respectively. Conclusion: Fracture-related infections are associated with significant mortality and morbidity regardless of depth and temporality. Non-MSSA FRIs are associated with inferior survival.

Cephalopod retinal development shows vertebrate-like mechanisms of neurogenesis.

Coleoid cephalopods, including squid, cuttlefish, and octopus, have large and complex nervous systems and high-acuity, camera-type eyes. These traits are comparable only to features that are independently evolved in the vertebrate lineage. The size of animal nervous systems and the diversity of their constituent cell types is a result of the tight regulation of cellular proliferation and differentiation in development. Changes in the process of development during evolution that result in a diversity of neural cell types and variable nervous system size are not well understood. Here, we have pioneered live-imaging techniques and performed functional interrogation to show that the squid Doryteuthis pealeii utilizes mechanisms during retinal neurogenesis that are hallmarks of vertebrate processes. We find that retinal progenitor cells in the squid undergo nuclear migration until they exit the cell cycle. We identify retinal organization corresponding to progenitor, post-mitotic, and differentiated cells. Finally, we find that Notch signaling may regulate both retinal cell cycle and cell fate. Given the convergent evolution of elaborate visual systems in cephalopods and vertebrates, these results reveal common mechanisms that underlie the growth of highly proliferative neurogenic primordia. This work highlights mechanisms that may alter ontogenetic allometry and contribute to the evolution of complexity and growth in animal nervous systems.

The burden of flashes and floaters in traditional general emergency services and utilization of ophthalmology on-call consultation: a cross-sectional study.

PURPOSE: To characterize the healthcare utilization and clinical characteristics of patients presenting with flashes and/or floaters (F/F) in general emergency service (GES) settings. METHODS: All adults presenting to GESs (emergency departments (EDs) and urgent care centers (UCCs)) with symptoms of F/F in Hamilton, Ontario between Jan. 1 - Dec. 31, 2018 were reviewed. Primary outcome was the proportion of patients presenting to GESs with F/F for which ophthalmology emergency services (OESs) were consulted. Secondary outcomes included features predictive of OES consultation by logistic regression and cost of GES utilization. RESULTS: Of 6590 primary eye-related visits to GESs, 10.4% (687) involved symptoms of F/F. Mean age of patients with F/F was 57 ± 15 years, and 61% were female. Consultation rate to OESs for F/F presentations was 89% (608/687). Logistic regression identified symptoms ≤ 2 weeks (OR 8.0; 95% CI 2.3-28), ≥ 45 years age (OR 2.4; 95% CI 1.4-4.3), UCC setting (OR 2.7; 95% CI 1.6-4.6), headache (OR 0.22; 95% CI 0.12-0.41), and neurologic symptoms (OR 0.1; 95% CI 0.19-0.49) as variables predictive of OES consultation. Mean time from triage to discharge in GESs for F/F patients was 2.43 ± 2.36 h. Mean cost per visit was $139.11 ± $113.93 Canadian dollars. Patients for which OES were consulted waited a total of 1345 h in GESs and accounted for $81,879.70 in costs. CONCLUSION: Patients presenting with F/F in GESs consume considerable resources in healthcare expenditure and time spent in GESs and most receive OES consultation. Identifying these patients at triage may allow for increased efficiency for the healthcare system and patients.

Human efficiency for classifying natural versus random text.

Humans are remarkably efficient at processing natural text. We quantified efficiency for discriminating a sample of meaningful text from a sample of random text by disrupting the meaningful sample, and measuring how much disruption human readers can tolerate before the two samples become indistinguishable. We performed these measurements for a wide range of conditions, involving samples of different lengths and containing letters, words or Chinese characters. We then compared human performance to the best possible performance achieved by a Bayesian estimator under the conditions in which we tested our participants, and in so doing we determined their absolute efficiency. Values were mostly in the range 5-40%, in agreement with reported efficiencies for many visual tasks. Although not intended as a veridical model of human processing, we found that the Bayesian model captured some (but not all) aspects of how humans classified text in our tasks and conditions.