A Physiological Analysis of Color Vision in Batoid Elasmobranchs

The potential for color vision in elasmobranchs has been studied in detail; however, a high degree of variation exists among the group. Evidence for ultraviolet (UV) vision is lacking, despite the presence of UV vision in every other vertebrate class. An integrative physiological approach was used to investigate color and ultraviolet vision in cownose rays and yellow stingrays, two batoids that inhabit different spectral environments. Both species had peaks in UV, short, medium, and long wavelength spectral regions in dark-, light-, and chromatic-adapted electroretinograms. Although no UV cones were found with microspectrophotometric analysis, both rays had multiple cone visual pigments with λmax at 470 and 551 nm in cownose rays (Rhinoptera bonasus) and 475, 533, and 562 nm in yellow stingrays (Urobatis jamaicensis). The same analysis demonstrated that both species had rod λmax at 500 and 499 nm, respectively. The lens and cornea of cownose rays maximally transmitted wavelengths greater than 350 nm and greater than 376 nm in yellow stingrays. These results support the potential for color vision in these species and future investigations should reveal the extent to which color discrimination is significant in a behavioral context

Programmable Attenuation of Antigenic Sensitivity for a Nanobody-Based EGFR Chimeric Antigen Receptor Through Hinge Domain Truncation

Epidermal growth factor family receptor (EGFR) is commonly overexpressed in many solid tumors and an attractive target for chimeric antigen receptor (CAR)-T therapy, but as EGFR is also expressed at lower levels in healthy tissues a therapeutic strategy must balance antigenic responsiveness against the risk of on-target off-tumor toxicity. Herein, we identify several camelid single-domain antibodies (also known as nanobodies) that are effective EGFR targeting moieties for CARs (EGFR-sdCARs) with very strong reactivity to EGFR-high and EGFR-low target cells. As a strategy to attenuate their potent antigenic sensitivity, we performed progressive truncation of the human CD8 hinge commonly used as a spacer domain in many CAR constructs. Single amino acid hinge-domain truncation progressively decreased both EGFR-sdCAR-Jurkat cell binding to EGFR-expressing targets and expression of the CD69 activation marker. Attenuated signaling in hinge-truncated EGFR-sdCAR constructs increased selectivity for antigen-dense EGFR-overexpressing cells over an EGFR-low tumor cell line or healthy donor derived EGFR-positive fibroblasts. We also provide evidence that epitope location is critical for determining hinge-domain requirement for CARs, as hinge truncation similarly decreased antigenic sensitivity of a membrane-proximal epitope targeting HER2-CAR but not a membrane-distal EGFRvIII-specific CAR. Hinge-modified EGFR-sdCAR cells showed clear functional attenuation in Jurkat-CAR-T cells and primary human CAR-T cells from multiple donors in vitro and in vivo. Overall, these results indicate that hinge length tuning provides a programmable strategy for throttling antigenic sensitivity in CARs targeting membrane-proximal epitopes, and could be employed for CAR-optimization and improved tumor selectivity

Police, public, and offender perceptions of body-worn video: a single jurisdictional multiple-perspective analysis

Objectives. Police, public, and offender survey responses from a single jurisdiction give a multiple-perspective insight into the use of body-worn video (BWV) cameras by police. Methods. Police attitudinal data was collected from before (n = 190), during (n = 139), and at the conclusion (n = 221) of a BWV implementation trial. Public attitudes were collected at the conclusion of the BWV implementation trial via online survey (n = 995 respondents) and intercept survey (n = 428 respondents). Offender attitudes (n = 302) were collected in police custody over a 6-month period immediately preceding the BWV trial. Results. The extent to which police felt BWV influenced their behavior tempered during the trial. All three perspectives were supportive of the use of BWV. The public who had encountered BWV-wearing officers and the offender sample indicated limited belief that BWV would reduce bad behavior. There was also clear contention about the policy and practice decisions around recording. Conclusions. These findings have significance for BWV trials, commenting on the importance of (a) collecting police attitudes at multiple points, (b) separating the attitudes of public who did encounter police wearing BWV, and (c) data collection and policy for evaluation outcomes

Multitaxonomic Diversity Patterns along a Desert Riparian–Upland Gradient

Riparian areas are noted for their high biodiversity, but this has rarely been tested across a wide range of taxonomic groups. We set out to describe species richness, species abundance, and community similarity patterns for 11 taxonomic groups (forbs & grasses, shrubs, trees, solpugids, spiders, scarab beetles, butterflies, lizards, birds, rodents, and mammalian carnivores) individually and for all groups combined along a riparian–upland gradient in semiarid southeastern Arizona, USA. Additionally, we assessed whether biological characteristics could explain variation in diversity along the gradient using five traits (trophic level, body size, life span, thermoregulatory mechanism, and taxonomic affiliation). At the level of individual groups diversity patterns varied along the gradient, with some having greater richness and/or abundance in riparian zones whereas others were more diverse and/or abundant in upland zones. Across all taxa combined, riparian zones contained significantly more species than the uplands. Community similarity between riparian and upland zones was low, and beta diversity was significantly greater than expected for most taxonomic groups, though biological traits explained little variance in diversity along the gradient. These results indicate heterogeneity amongst taxa in how they respond to the factors that structure ecological communities in riparian landscapes. Nevertheless, across taxonomic groups the overall pattern is one of greater species richness and abundance in riparian zones, coupled with a distinct suite of species

Molecular regulation of auditory hair cell death and approaches to protect sensory receptor cells and/or stimulate repair following acoustic trauma

International audienceLoss of auditory sensory hair cells (HCs) is the most common cause of hearing loss. This review addresses the signaling pathways that are involved in the programmed and necrotic cell death of auditory HCs that occur in response to ototoxic and traumatic stressor events. The roles of inflammatory processes, oxidative stress, mitochondrial damage, cell death receptors, members of the mitogen-activated protein kinase (MAPK) signal pathway and pro- and anti-cell death members of the Bcl-2 family are explored. The molecular interaction of these signal pathways that initiates the loss of auditory HCs following acoustic trauma is covered and possible therapeutic interventions that may protect these sensory HCs from loss via apoptotic or non-apoptotic cell death are explored

Effects of Temperature and Anesthesia on Visual Temporal Resolution in Elasmobranch Fishes

An organism’s ability to track moving objects, or temporal resolution, has been correlated to habitat and lifestyle, and can be further modulated by temperature and light intensity fluctuations within the environment. Photopic (bright-light/day time) vision is typically faster than scotopic (dim-light/night time) because visual sensitivity is greater in dim light and integration time must be slowed to allow for capture of the maximum number of photons. Higher temperatures result in increased temporal resolution in both endothermic and non-endothermic fishes. Previous studies have used either anesthetized or paralyzed fishes to determine temporal resolution, measured as the maximum critical flicker fusion frequency (CFFmax). However, sedation with the anesthetic, tricaine methanesulfonate (MS-222), is thought to suppress sensory system responses, although empirical evidence is lacking. Therefore, we quantified scotopic and photopic CFFmax in the yellow stingray, Urobatis jamaicensis, at the extremes of its temperature range, 20°C and 30°C, and immobilized with anesthesia, MS-222, or a paralytic, Pavulon. Both low temperature and anesthesia (MS-222) reduced CFFmax. With an increase of 10°C, CFFmax doubled from 12Hz to 25.3Hz (photopic) under Pavulon, whereas CFFmax increased by only 4Hz, from 6.7Hz to 10.7Hz (photopic) under MS-222 anesthesia. In general, MS-222 anesthesia minimized the effects of both temperature and light-adaptation compared to Pavulon. Yellow stingray CFFmax was similar to the skate, another benthic batoid, but slower than shark species studied with the same technique. These results illustrate the effects of light adaptation, temperature, and anesthesia on visual function within the elasmobranch fishes