Interspecies sex and taste.

Different species of fruit flies share habitats but are believed to mate with each other only rarely. In this issue, Fan et al. show that interspecies mating is inhibited by the taste receptor Gr32a (Gustatory receptor 32a) and a neural circuit in which it functions.

Half a century of global decline in oceanic sharks and rays.

Overfishing is the primary cause of marine defaunation, yet declines in and increasing extinction risks of individual species are difficult to measure, particularly for the largest predators found in the high seas1-3. Here we calculate two well-established indicators to track progress towards Aichi Biodiversity Targets and Sustainable Development Goals4,5: the Living Planet Index (a measure of changes in abundance aggregated from 57 abundance time-series datasets for 18 oceanic shark and ray species) and the Red List Index (a measure of change in extinction risk calculated for all 31 oceanic species of sharks and rays). We find that, since 1970, the global abundance of oceanic sharks and rays has declined by 71% owing to an 18-fold increase in relative fishing pressure. This depletion has increased the global extinction risk to the point at which three-quarters of the species comprising this functionally important assemblage are threatened with extinction. Strict prohibitions and precautionary science-based catch limits are urgently needed to avert population collapse6,7, avoid the disruption of ecological functions and promote species recovery8,9.

Exitron splicing of odor receptor genes in Drosophila.

Proper expression of odor receptor genes is critical for the function of olfactory systems. In this study, we identified exitrons (exonic introns) in four of the 39 Odorant receptor (Or) genes expressed in the Drosophila antenna. Exitrons are sequences that can be spliced out from within a protein-coding exon, thereby altering the encoded protein. We focused on Or88a, which encodes a pheromone receptor, and found that exitron splicing of Or88a is conserved across five Drosophila species over 20 My of evolution. The exitron was spliced out in 15% of Or88a transcripts. Removal of this exitron creates a non-coding RNA rather than an RNA that encodes a stable protein. Our results suggest the hypothesis that in the case of Or88a, exitron splicing could act in neuronal modulation by decreasing the level of functional Or transcripts. Activation of Or88a-expressing olfactory receptor neurons via either optogenetics or pheromone stimulation increased the level of exitron-spliced transcripts, with optogenetic activation leading to a 14-fold increase. A fifth Or can also undergo an alternative splicing event that eliminates most of the canonical open reading frame. Besides these cases of alternative splicing, we found alternative polyadenylation of four Ors, and exposure of Or67c to its ligand ethyl lactate in the antenna downregulated all of its 3' isoforms. Our study reveals mechanisms by which neuronal activity could be modulated via regulation of the levels of Or isoforms.

Conservation successes and challenges for wide-ranging sharks and rays.

Overfishing is the most significant threat facing sharks and rays. Given the growth in consumption of seafood, combined with the compounding effects of habitat loss, climate change, and pollution, there is a need to identify recovery paths, particularly in poorly managed and poorly monitored fisheries. Here, we document conservation through fisheries management success for 11 coastal sharks in US waters by comparing population trends through a Bayesian state-space model before and after the implementation of the 1993 Fisheries Management Plan for Sharks. We took advantage of the spatial and temporal gradients in fishing exposure and fisheries management in the Western Atlantic to analyze the effect on the Red List status of all 26 wide-ranging coastal sharks and rays. We show that extinction risk was greater where fishing pressure was higher, but this was offset by the strength of management engagement (indicated by strength of National and Regional Plan of Action for sharks and rays). The regional Red List Index (which tracks changes in extinction risk through time) declined in all regions until the 1980s but then improved in the North and Central Atlantic such that the average extinction risk is currently half that in the Southwest. Many sharks and rays are wide ranging, and successful fisheries management in one country can be undone by poorly regulated or unregulated fishing elsewhere. Our study underscores that well-enforced, science-based management of carefully monitored fisheries can achieve conservation success, even for slow-growing species.

Meeting a threat of the Anthropocene: Taste avoidance of metal ions by Drosophila.

The Anthropocene Epoch poses a critical challenge for organisms: they must cope with new threats at a rapid rate. These threats include toxic chemical compounds released into the environment by human activities. Here, we examine elevated concentrations of heavy metal ions as an example of anthropogenic stressors. We find that the fruit fly Drosophila avoids nine metal ions when present at elevated concentrations that the flies experienced rarely, if ever, until the Anthropocene. We characterize the avoidance of feeding and egg laying on metal ions, and we identify receptors, neurons, and taste organs that contribute to this avoidance. Different subsets of taste receptors, including members of both Ir (Ionotropic receptor) and Gr (Gustatory receptor) families contribute to the avoidance of different metal ions. We find that metal ions activate certain bitter-sensing neurons and inhibit sugar-sensing neurons. Some behavioral responses are mediated largely through neurons of the pharynx. Feeding avoidance remains stable over 10 generations of exposure to copper and zinc ions. Some responses to metal ions are conserved across diverse dipteran species, including the mosquito Aedes albopictus. Our results suggest mechanisms that may be essential to insects as they face challenges from environmental changes in the Anthropocene.

Fungal Sensitization and Human Allergic Disease.

PURPOSE OF THE REVIEW: Fungal sensitizations have been associated with hypersensitivity reactions with variable levels of evidence available to link types of fungi with human disease. We conducted systematic reviews of the literature to identify the strength of evidence linking lesser-studied fungi for which there are commercially available extracts to identify populations in which they were useful in clinical practice. RECENT FINDINGS: Excluding five fungi for which hundreds of articles were identified, there are 54 articles on the remaining fungi with clinical data. For 12 of the fungi, the prevalence of fungal sensitization varies in different hypersensitivity disorders due to factors related to geographic areas, age, and other underlying medical conditions. There were no studies linking seven genera to human disease. Most of the commercially available fungal extracts are uncommonly associated with hypersensitivity reactions in humans. Specific extracts may be useful in particular disease states such as allergic fungal sinusitis or allergic bronchopulmonary mycosis, or when routine testing fails to identify a cause of uncontrolled disease, such as in asthma.

Olfactory perception: receptors, cells, and circuits.

Remarkable advances in our understanding of olfactory perception have been made in recent years, including the discovery of new mechanisms of olfactory signaling and new principles of olfactory processing. Here, we discuss the insight that has been gained into the receptors, cells, and circuits that underlie the sense of smell.

The mosquito taste system and disease control.

Mosquitoes are a widely diverse group of organisms, comprising ∼3,500 species that live in an enormous range of habitats. Some species are vectors of diseases that afflict hundreds of millions of people each year. Although understanding of mosquito olfaction has progressed dramatically in recent years, mosquito taste remains greatly understudied. Since taste is essential to feeding, egg laying, and mating decisions in insects, improved understanding of taste in mosquitoes could provide new mechanistic insight into many aspects of their behavior. We provide a guide to current knowledge in the field, and we suggest a wealth of opportunities for research that are now enabled by recent scientific and technological advances. We also propose means by which taste might be exploited in new strategies for mosquito control, which may be urgently needed as the geographical ranges of vector species increase with climate change.

Age, growth and maturity of the yellow stingray (Urobatis jamaicensis), a biannually reproductive tropical batoid.

Urobatis jamaicensis is a coastal batoid species affected by habitat loss and small-scale exploitation from fisheries and the aquarium trade, yet the life-history information available is limited. This is the first study to assess the vertebral centra from 195 stingrays to estimate age and growth patterns, and compare them with the biannual reproductive pattern previously reported for this species. Age-at-size data were compared using five different growth models and found a two-parameter von Bertalanffy growth function (VBGF), the Gompertz model and a modified VBGF fit best for males, females and sexes combined, respectively. Maturity was achieved before 1 year. However, growth did not cease with the onset of maturity, but instead slowed down. Results from marginal increment analysis and edge analysis indicated a nonannual somatic growth pattern with influences from the biannual reproduction cycle where peaks in resource allocation may be focused on ovulation rather than growth during March when larger brood sizes are present, while resources may be allocated more towards growth during August and September when brood sizes are generally smaller. These results may be used as a proxy for species with similar reproductive patterns or for those that lack annual or seasonal growth patterns.

Observations of fin injury closure in Great Hammerheads and implications for the use of fin-mounted geolocators.

OBJECTIVE: Sharks face a high risk of injuries throughout all life stages and are therefore expected to show a good wound closure capacity. METHODS: Here, the wound closure of one major injury and one minor injury to the first dorsal fins of two free-ranging, mature female Great Hammerheads Sphyrna mokarran is described macroscopically. RESULT: The sharks showed complete wound closure of single, clean-cut lacerations measuring 24.2 and 11.6 cm in length after an estimated 323 and 138 days. These estimates were based on the observed closure rate and visual confirmation of a complete wound closure upon multiple resightings of the same individuals. Additionally, the posterior lateral displacement of fin-mounted geolocators within the fin and outside of the fin without causing external damage was documented in three additional Great Hammerheads. CONCLUSION: These observations supplement findings about wound closure capabilities in elasmobranchs. The documented geolocator displacement furthers the discussion about the safe use of these geolocators to track shark movements but also has implications for future tagging studies.

Host genomic influence on bacterial composition in the switchgrass rhizosphere.

Host genetic variation can shape the diversity and composition of associated microbiomes, which may reciprocally influence host traits and performance. While the genetic basis of phenotypic diversity of plant populations in nature has been studied, comparatively little research has investigated the genetics of host effects on their associated microbiomes. Switchgrass (Panicum virgatum) is a highly outcrossing, perennial, grass species with substantial locally adaptive diversity across its native North American range. Here, we compared 383 switchgrass accessions in a common garden to determine the host genotypic influence on rhizosphere bacterial composition. We hypothesized that the composition and diversity of rhizosphere bacterial assemblages would differentiate due to genotypic differences between hosts (potentially due to root phenotypes and associated life history variation). We observed higher alpha diversity of bacteria associated with upland ecotypes and tetraploids, compared to lowland ecotypes and octoploids, respectively. Alpha diversity correlated negatively with flowering time and plant height, indicating that bacterial composition varies along switchgrass life history axes. Narrow-sense heritability (h2 ) of the relative abundance of 21 core bacterial families was observed. Overall compositional differences among tetraploids, due to genetic variation, supports widespread genotypic influence on the rhizosphere microbiome. Tetraploids were only considered due to complexities associated with the octoploid genomes. Lastly, a genome-wide association study identified 1861 single-nucleotide polymorphisms associated with 110 families and genes containing them related to potential regulatory functions. Our findings suggest that switchgrass genomic and life-history variation influences bacterial composition in the rhizosphere, potentially due to host adaptation to local environments.

Female sex is associated with reintervention and mortality following elective endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Although sex differences in endovascular abdominal aortic aneurysm repair (EVAR) outcomes have been increasingly reported, the determination of contributing factors has not reached a consensus. We investigated the disparities in sex-specific outcomes after elective EVAR at our institution and evaluated the factors that might predispose women to increased morbidity and mortality. METHODS: We performed a retrospective medical record review of all patients who had undergone elective EVAR from 2011 to 2020 at a suburban tertiary care center. The primary outcomes were 5-year survival and freedom from reintervention. The Fisher exact test, t tests, and Kaplan-Meier analysis using the rank-log test were used to investigate the associations between sex and outcomes. A multivariable Cox proportional hazard model controlling for age and common comorbidities evaluated the effect of sex on survival and freedom from reintervention. RESULTS: A total of 273 patients had undergone elective EVAR during the study period, including 68 women (25%) and 205 men (75%). The women were older on average than were than the men (76 years vs 73 years; P ≤ .01) and were more likely to have chronic obstructive pulmonary disease (38% vs 23%; P = .01), require home oxygen therapy (9% vs 2%; P = .04), or dialysis preoperatively (4% vs 0%; P = .02). The distribution of other common vascular comorbidities was similar between the sexes. The 30-day readmission rate was greater for the women than for the men (18% vs 8%; P = .02). The women had had significantly lower survival at 5 years (48% ± 7.9% vs 65% ± 4.3%; P < .01) and significantly lower 1-year (women, 89% ± 4.1%; vs men, 94% ± 1.7%; P = .01) and 5-year (women, 69% ± 8.9%; vs men, 84% ± 3.3%; P = .02) freedom from reintervention. On multivariable analysis, female sex (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9), congestive heart failure (HR, 2.2; 95% CI, 1.2-3.9), and older age (HR, 1.1; 95% CI, 1.0-1.1) were associated with 5-year mortality. Female sex remained as the only variable with a statistically significant association with 5-year reintervention (HR, 2.4; 95% CI, 1.1-4.9). CONCLUSIONS: Female sex was associated with decreased 5-year survival and increased 1- and 5-year reintervention after elective EVAR. Data from our institution suggest that factors beyond patient age and baseline health risk likely contribute to greater surgical morbidity and mortality for women after elective EVAR.

Chemosensory sensilla of the Drosophila wing express a candidate ionotropic pheromone receptor.

The Drosophila wing was proposed to be a taste organ more than 35 years ago, but there has been remarkably little study of its role in chemoreception. We carry out a differential RNA-seq analysis of a row of sensilla on the anterior wing margin and find expression of many genes associated with pheromone and chemical perception. To ask whether these sensilla might receive pheromonal input, we devised a dye-transfer paradigm and found that large, hydrophobic molecules comparable to pheromones can be transferred from one fly to the wing margin of another. One gene, Ionotropic receptor (IR)52a, is coexpressed in neurons of these sensilla with fruitless, a marker of sexual circuitry; IR52a is also expressed in legs. Mutation of IR52a and optogenetic silencing of IR52a+ neurons decrease levels of male sexual behavior. Optogenetic activation of IR52a+ neurons induces males to show courtship toward other males and, remarkably, toward females of another species. Surprisingly, IR52a is also required in females for normal sexual behavior. Optogenetic activation of IR52a+ neurons in mated females induces copulation, which normally occurs at very low levels. Unlike other chemoreceptors that act in males to inhibit male-male interactions and promote male-female interactions, IR52a acts in both males and females, and can promote male-male as well as male-female interactions. Moreover, IR52a+ neurons can override the circuitry that normally suppresses sexual behavior toward unproductive targets. Circuit mapping and Ca2+ imaging using the trans-Tango system reveals second-order projections of IR52a+ neurons in the subesophageal zone (SEZ), some of which are sexually dimorphic. Optogenetic activation of IR52a+ neurons in the wing activates second-order projections in the SEZ. Taken together, this study provides a molecular description of the chemosensory sensilla of a greatly understudied taste organ and defines a gene that regulates the sexual circuitry of the fly.

Cognitive behavioral treatments for children and adolescents exposed to traumatic events: A meta-analysis examining variables moderating treatment outcomes.

Due to the negative impact of trauma exposure, effective treatments are necessary to prevent and improve negative trauma-related outcomes. Cognitive behavioral therapy (CBT) is considered an efficacious treatment for children and adolescents exposed to traumatic events. Despite the various meta-analyses that have examined trauma treatments, there is a paucity of research on the moderating variables that may impact treatment outcomes. This meta-analytic CBT study addressed those limitations by examining the moderating effects of treatment components on outcomes. A search identified 94 CBT studies with 97 relevant effect sizes for children and adolescents exposed to traumatic events. Consistent with prior meta-analytic studies, CBT was shown to be effective for trauma-exposed youth. CBT subtreatments did not produce significantly different results from one another. Moderators shown to significantly impact CBT treatment outcomes for posttraumatic stress symptom were trauma type, Q = 24.09, p = .004, ds = -0.22 to -1.42, and gender, Q = 10.68, p = .005, ds = -0.53 to -1.36, whereas moderators shown to impact treatment outcomes for depression were study design, Q = 10.95, p = .004, ds = -0.26 to -0.50, and treatment setting, Q = 10.98, p = .004, ds = -0.31 to -0.56. The implications of these findings for research and practice are discussed.

Odor coding in the antenna of the tsetse fly Glossina morsitans.

Tsetse flies transmit trypanosomiasis to humans and livestock across much of sub-Saharan Africa. Tsetse are attracted by olfactory cues emanating from their hosts. However, remarkably little is known about the cellular basis of olfaction in tsetse. We have carried out a systematic physiological analysis of the Glossina morsitans antenna. We identify 7 functional classes of olfactory sensilla that respond to human or animal odorants, CO2, sex and alarm pheromones, or other odorants known to attract or repel tsetse. Sensilla differ in their response spectra, show both excitatory and inhibitory responses, and exhibit different response dynamics to different odor stimuli. We find striking differences between the functional organization of the tsetse fly antenna and that of the fruit fly Drosophila melanogaster One morphological type of sensilla has a different function in the 2 species: Trichoid sensilla respond to pheromones in Drosophila but respond to a wide diversity of compounds in G. morsitans. In contrast to Drosophila, all tested G. morsitans sensilla that show excitatory responses are excited by one odorant, 1-octen-3-ol, which is contained in host emanations. The response profiles of some classes of sensilla are distinct but strongly correlated, unlike the organization described in the Drosophila antenna. Taken together, this study defines elements that likely mediate the attraction of tsetse to its hosts and that might be manipulated as a means of controlling the fly and the diseases it transmits.

The molecular and cellular basis of olfactory response to tsetse fly attractants.

Dipteran or "true" flies occupy nearly every terrestrial habitat, and have evolved to feed upon a wide variety of sources including fruit, pollen, decomposing animal matter, and even vertebrate blood. Here we analyze the molecular, genetic and cellular basis of odor response in the tsetse fly Glossina morsitans, which feeds on the blood of humans and their livestock, and is a vector of deadly trypanosomes. The G. morsitans antenna contains specialized subtypes of sensilla, some of which line a sensory pit not found in the fruit fly Drosophila. We characterize distinct patterns of G. morsitans Odor receptor (GmmOr) gene expression in the antenna. We devise a new version of the "empty neuron" heterologous expression system, and use it to functionally express several GmmOrs in a mutant olfactory receptor neuron (ORN) of Drosophila. GmmOr35 responds to 1-hexen-3-ol, an odorant found in human emanations, and also alpha-pinene, a compound produced by malarial parasites. Another receptor, GmmOr9, which is expressed in the sensory pit, responds to acetone, 2-butanone and 2-propanol. We confirm by electrophysiological recording that neurons of the sensory pit respond to these odorants. Acetone and 2-butanone are strong attractants long used in the field to trap tsetse. We find that 2-propanol is also an attractant for both G. morsitans and the related species G. fuscipes, a major vector of African sleeping sickness. The results identify 2-propanol as a candidate for an environmentally friendly and practical tsetse attractant. Taken together, this work characterizes the olfactory system of a highly distinct kind of fly, and it provides an approach to identifying new agents for controlling the fly and the devastating diseases that it carries.

Dynamic Intracranial Pressure Waveform Morphology Predicts Ventriculitis.

BACKGROUND: Intracranial pressure waveform morphology reflects compliance, which can be decreased by ventriculitis. We investigated whether morphologic analysis of intracranial pressure dynamics predicts the onset of ventriculitis. METHODS: Ventriculitis was defined as culture or Gram stain positive cerebrospinal fluid, warranting treatment. We developed a pipeline to automatically isolate segments of intracranial pressure waveforms from extraventricular catheters, extract dominant pulses, and obtain morphologically similar groupings. We used a previously validated clinician-supervised active learning paradigm to identify metaclusters of triphasic, single-peak, or artifactual peaks. Metacluster distributions were concatenated with temperature and routine blood laboratory values to create feature vectors. A L2-regularized logistic regression classifier was trained to distinguish patients with ventriculitis from matched controls, and the discriminative performance using area under receiver operating characteristic curve with bootstrapping cross-validation was reported. RESULTS: Fifty-eight patients were included for analysis. Twenty-seven patients with ventriculitis from two centers were identified. Thirty-one patients with catheters but without ventriculitis were selected as matched controls based on age, sex, and primary diagnosis. There were 1590 h of segmented data, including 396,130 dominant pulses in patients with ventriculitis and 557,435 pulses in patients without ventriculitis. There were significant differences in metacluster distribution comparing before culture-positivity versus during culture-positivity (p < 0.001) and after culture-positivity (p < 0.001). The classifier demonstrated good discrimination with median area under receiver operating characteristic 0.70 (interquartile range 0.55-0.80). There were 1.5 true alerts (ventriculitis detected) for every false alert. CONCLUSIONS: Intracranial pressure waveform morphology analysis can classify ventriculitis without cerebrospinal fluid sampling.

Thirty-five years of tiger shark Galeocerdo cuvier relative abundance near Bimini, The Bahamas, and the Southeastern United States with a comparison across jurisdictional bounds.

Abundances of large sharks are reported to have declined worldwide, and in response various levels of fisheries management and conservation efforts have been established. For example, marine-protected areas have been suggested as a means to protect large expanses of ocean from fishing and other industrial activities (e.g., habitat destruction), and in 2011 The Commonwealth of The Bahamas established The Bahamas Shark Sanctuary. Nonetheless, assessing the effectiveness of conservation efforts is challenging because consistent long-term data sets of shark abundances are often lacking, especially throughout the Caribbean and The Bahamas. In this study, the authors investigated the catch rates and demographics of tiger sharks Galeocerdo cuvier caught in a fishery-independent survey near Bimini, The Bahamas, from 1984 to 2019 to assess relative abundance trends following the banning of longline fishing in 1993 and the subsequent establishment of the shark sanctuary. To contextualize the relative abundance trends near Bimini, the authors compared this to the relative abundance of tiger sharks in a fishery-dependent survey from the Southeastern USA (SE USA), conducted from 1994 to 2019. The data of this study suggest that local abundance of tiger sharks has been stable near Bimini since the 1980s, including after the ban of longline fishing and the implementation of the shark sanctuary. In comparison, the abundance near the SE USA has slowly increased in the past decade, following potential declines in the decade preceding the USA Shark Management Plan. The results of this study provide some optimism that current conservation efforts in The Bahamas have been effective to maintain local tiger shark abundance within the protected area. In addition, current fisheries management in the SE USA is allowing this species to recover within those waters.

Best Practices for Conducting Clinical Trials With Indigenous Children in the United States.

We provide guidance for conducting clinical trials with Indigenous children in the United States. We drew on extant literature and our experience to describe 3 best practices for the ethical and effective conduct of clinical trials with Indigenous children. Case examples of pediatric research conducted with American Indian, Alaska Native, and Native Hawaiian communities are provided to illustrate these practices. Ethical and effective clinical trials with Indigenous children require early and sustained community engagement, building capacity for Indigenous research, and supporting community oversight and ownership of research. Effective engagement requires equity, trust, shared interests, and mutual benefit among partners over time. Capacity building should prioritize developing Indigenous researchers. Supporting community oversight and ownership of research means that investigators should plan for data-sharing agreements, return or destruction of data, and multiple regulatory approvals. Indigenous children must be included in clinical trials to reduce health disparities and improve health outcomes in these pediatric populations. Establishment of the Environmental Influences on Child Health Outcomes Institutional Development Award States Pediatric Clinical Trials Network (ECHO ISPCTN) in 2016 creates a unique and timely opportunity to increase Indigenous children's participation in state-of-the-art clinical trials.

Transcriptome profiles of Quercus rubra responding to increased O3 stress.

BACKGROUND: Climate plays an essential role in forest health, and climate change may increase forest productivity losses due to abiotic and biotic stress. Increased temperature leads to the increased formation of ozone (O3). Ozone is formed by the interaction of sunlight, molecular oxygen and by the reactions of chemicals commonly found in industrial and automobile emissions such as nitrogen oxides and volatile organic compounds. Although it is well known that productivity of Northern red oak (Quercus rubra) (NRO), an ecologically and economically important species in the forests of eastern North America, is reduced by exposure to O3, limited information is available on its responses to exogenous stimuli at the level of gene expression. RESULTS: RNA sequencing yielded more than 323 million high-quality raw sequence reads. De novo assembly generated 52,662 unigenes, of which more than 42,000 sequences could be annotated through homology-based searches. A total of 4140 differential expressed genes (DEGs) were detected in response to O3 stress, as compared to their respective controls. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the O3-response DEGs revealed perturbation of several biological pathways including energy, lipid, amino acid, carbohydrate and terpenoid metabolism as well as plant-pathogen interaction. CONCLUSION: This study provides the first reference transcriptome for NRO and initial insights into the genomic responses of NRO to O3. Gene expression profiling reveals altered primary and secondary metabolism of NRO seedlings, including known defense responses such as terpenoid biosynthesis.