Conservation of magnetite biomineralization genes in all domains of life and implications for magnetic sensing.

Animals use geomagnetic fields for navigational cues, yet the sensory mechanism underlying magnetic perception remains poorly understood. One idea is that geomagnetic fields are physically transduced by magnetite crystals contained inside specialized receptor cells, but evidence for intracellular, biogenic magnetite in eukaryotes is scant. Certain bacteria produce magnetite crystals inside intracellular compartments, representing the most ancient form of biomineralization known and having evolved prior to emergence of the crown group of eukaryotes, raising the question of whether magnetite biomineralization in eukaryotes and prokaryotes might share a common evolutionary history. Here, we discover that salmonid olfactory epithelium contains magnetite crystals arranged in compact clusters and determine that genes differentially expressed in magnetic olfactory cells, contrasted to nonmagnetic olfactory cells, share ancestry with an ancient prokaryote magnetite biomineralization system, consistent with exaptation for use in eukaryotic magnetoreception. We also show that 11 prokaryote biomineralization genes are universally present among a diverse set of eukaryote taxa and that nine of those genes are present within the Asgard clade of archaea Lokiarchaeota that affiliates with eukaryotes in phylogenomic analysis. Consistent with deep homology, we present an evolutionary genetics hypothesis for magnetite formation among eukaryotes to motivate convergent approaches for examining magnetite-based magnetoreception, molecular origins of matrix-associated biomineralization processes, and eukaryogenesis.

Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations.

Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.

Development of a scale for measuring physician attitudes toward interprofessional education and collaboration.

Interest has been increasing in interprofessional education and collaboration (IPEC) within health professional schools over the last two decades. Although a growing body of literature addresses the effects of IPEC on healthcare outcomes, psychometrically sound attitudinal instruments that measure concepts surrounding IPEC are still needed. The primary objective of this study was to develop a scale to measure the attitudes of attending physicians and residents toward IPEC. Based on a literature review, a set of questionnaire items was drafted to address all six domains outlined in a World Health Organization report for interprofessional learning outcomes. These domains are teamwork and collaboration, roles and responsibilities, communication, reflection and learning, the patient, and ethics and attitudes. A total of 379 physicians and trainees completed the questionnaire. A principal axis factoring with orthogonal varimax rotation of 20 items produced a 5-factor solution explaining 60% of the variance. Examination of the items in each factor led to the following labels: 'teamwork and communication,' 'ethics and attitudes,' 'roles and responsibilities,' 'reflective practice,' and 'patient-centered care.' A Generalized Linear Model provided initial evidence that the new scale might detect shifts in attitudes related to some of the emergent factors.

Local Treatment of Non-small Cell Lung Cancer with a Spray-Dried Bevacizumab Formulation.

Local delivery of biotherapeutics to the lung holds great promise for treatment of lung diseases, but development of physically stable, biologically active dry powder formulations of large molecules for inhalation has remained a challenge. Here, spray drying was used to manufacture a dry powder pulmonary formulation of bevacizumab, a monoclonal antibody approved to treat non-small cell lung cancer (NSCLC) by intravenous infusion. By reformulating bevacizumab for local delivery, reduced side effects, lower doses, and improved patient compliance are possible. The formulation had aerosol properties suitable for delivery to the deep lung, as well as good physical stability at ambient temperature for at least 6 months. Bevacizumab's anti-VEGF bioactivity was not impacted by the manufacturing process. The formulation was efficacious in an in vivo rat model for NSCLC at a 10-fold decrease in dose relative to the intravenous control.

Long-term aggregation of larval fish siblings during dispersal along an open coast.

Pelagic dispersal of most benthic marine organisms is a fundamental driver of population distribution and persistence and is thought to lead to highly mixed populations. However, the mechanisms driving dispersal pathways of larvae along open coastlines are largely unknown. To examine the degree to which early stages can remain spatially coherent during dispersal, we measured genetic relatedness within a large pulse of newly recruited splitnose rockfish (Sebastes diploproa), a live-bearing fish whose offspring settle along the US Pacific Northwest coast after spending up to a year in the pelagic environment. A total of 11.6% of the recruits in a single recruitment pulse were siblings, providing the first evidence for persistent aggregation throughout a long dispersal period. Such protracted aggregation has profound implications for our understanding of larval dispersal, population connectivity, and gene flow within demersal marine populations.

The prevalence of long QT interval in post-operative intensive care unit patients.

The severity of patient illnesses and medication complexity in post-operative critically ill patients increase the risk for a prolonged QT interval. We determined the prevalence of prolonged QTc in surgical intensive care unit (SICU) patients. We performed a prospective cross-sectional study over a 15-month period at a major academic center. SICU pre-admission and admission EKGs, patient demographics, and laboratory values were analyzed. QTc was evaluated as both a continuous and dichotomous outcome (prolonged QTc > 440 ms). 281 patients were included in the study: 92 % (n = 257) post-operative and 8 % (n = 24) non-operative. On pre-admission EKGs, 32 % of the post-operative group and 42 % of the non-operative group had prolonged QTc (p = 0.25); on post-admission EKGs, 67 % of the post-operative group but only 33 % of the non-operative group had prolonged QTc (p < 0.01). The average change in QTc in the post-operative group was +30.7 ms, as compared to +2 ms in the non-operative group (p < 0.01). On multivariable adjustment for long QTc as a dichotomous outcome, pre-admission prolonged QTc (OR 3.93, CI 1.93-8.00) and having had an operative procedure (OR 4.04, CI 1.67-9.83) were associated with developing prolonged QTc. For QTc as a continuous outcome, intra-operative beta-blocker use was associated with a statistically-significant decrease in QTc duration. None of the patients developed a lethal arrhythmia in the ICU. Prolonged QTc is common among post-operative SICU patients (67 %), however lethal arrhythmias are uncommon. The operative experience increases the risk for long QTc.

Testing advances in molecular discrimination among Chinook salmon life histories: evidence from a blind test.

The application of DNA-based markers toward the task of discriminating among alternate salmon runs has evolved in accordance with ongoing genomic developments and increasingly has enabled resolution of which genetic markers associate with important life-history differences. Accurate and efficient identification of the most likely origin for salmon encountered during ocean fisheries, or at salvage from fresh water diversion and monitoring facilities, has far-reaching consequences for improving measures for management, restoration and conservation. Near-real-time provision of high-resolution identity information enables prompt response to changes in encounter rates. We thus continue to develop new tools to provide the greatest statistical power for run identification. As a proof of concept for genetic identification improvements, we conducted simulation and blind tests for 623 known-origin Chinook salmon (Oncorhynchus tshawytscha) to compare and contrast the accuracy of different population sampling baselines and microsatellite loci panels. This test included 35 microsatellite loci (1266 alleles), some known to be associated with specific coding regions of functional significance, such as the circadian rhythm cryptochrome genes, and others not known to be associated with any functional importance. The identification of fall run with unprecedented accuracy was demonstrated. Overall, the top performing panel and baseline (HMSC21) were predicted to have a success rate of 98%, but the blind-test success rate was 84%. Findings for bias or non-bias are discussed to target primary areas for further research and resolution.

Control of soft robots with inertial dynamics.

Soft robots promise improved safety and capability over rigid robots when deployed near humans or in complex, delicate, and dynamic environments. However, infinite degrees of freedom and the potential for highly nonlinear dynamics severely complicate their modeling and control. Analytical and machine learning methodologies have been applied to model soft robots but with constraints: quasi-static motions, quasi-linear deflections, or both. Here, we advance the modeling and control of soft robots into the inertial, nonlinear regime. We controlled motions of a soft, continuum arm with velocities 10 times larger and accelerations 40 times larger than those of previous work and did so for high-deflection shapes with more than 110° of curvature. We leveraged a data-driven learning approach for modeling, based on Koopman operator theory, and we introduce the concept of the static Koopman operator as a pregain term in optimal control. Our approach is rapid, requiring less than 5 min of training; is computationally low cost, requiring as little as 0.5 s to build the model; and is design agnostic, learning and accurately controlling two morphologically different soft robots. This work advances rapid modeling and control for soft robots from the realm of quasi-static to inertial, laying the groundwork for the next generation of compliant and highly dynamic robots.

Ventilator Training through International Telesimulation in Sierra Leone.

Background: The coronavirus disease (COVID-19) pandemic resulted in an increased need for medical professionals with expertise in managing patients with acute hypoxemic respiratory failure, overwhelming the existing critical care workforce in many low-resource countries. Objective: To address this need in Sierra Leone, we developed, piloted, and evaluated a synchronous simulation-based tele-education workshop for healthcare providers on the fundamental principles of intensive care unit (ICU) management of the COVID-19 patient in a low-resource setting. Methods: Thirteen 2-day virtual workshops were implemented between April and July 2020 with frontline Sierra Leone physicians and nurses for potential ICU patients in hospitals throughout Sierra Leone. Although all training sessions took place at the 34 Military Hospital (a national COVID-19 center) in Freetown, participants were drawn from hospitals in each of the provinces of Sierra Leone. The workshops included synchronous tele-education-directed medical simulation didactic sessions about COVID-19, hypoxemia management, and hands-on simulation training about mechanical ventilation. Measures included pre and postworkshop knowledge tests, simulation checklists, and a posttest survey. Test results were analyzed with a paired sample t test; Likert-scale survey responses were reported using descriptive statistics; and open-ended responses were analyzed using thematic analysis. Results: Seventy-five participants enrolled in the program. On average, participants showed 20.8% improvement (a score difference of 4.00 out of a maximum total score of 20) in scores between pre and postworkshop knowledge tests (P = 0.004). Participants reported satisfaction with training (96%; n = 73), achieved 100% of simulation checklist objectives, and increased confidence with ventilator skills (96%; n = 73). Themes from the participants' feedback included increased readiness to train colleagues on critical care ventilators at their hospitals, the need for longer and more frequent training, and a need to have access to critical care ventilators at their hospitals. Conclusion: This synchronous tele-education-directed medical simulation workshop implemented through partnerships between U.S. physicians and Sierra Leone healthcare providers was a feasible, acceptable, and effective means of providing training about COVID-19, hypoxemia management, and mechanical ventilation. Future ICU ventilator training opportunities may consider increasing the length of training beyond 2 days to allow more time for the hands-on simulation scenarios using the ICU ventilator and assessing knowledge application in long-term follow-up.

Assessing population-level variation in the mitochondrial genome of Euphausia superba using 454 next-generation sequencing.

The Antarctic krill (Euphausia superba Dana 1852) is widely distributed throughout the Southern Ocean, where it provides a key link between primary producers and upper trophic levels and supports a major commercial fishery. Despite its ecological and commercial importance, genetic population structure of the Antarctic krill remains poorly described. In an attempt to illuminate genetic markers for future population and phylogenetic analysis, five E. superba mitogenomes, from samples collected west of the Antarctic Peninsula, were sequenced using new 454 next-generation sequencing techniques. The sequences, of lengths between 13,310 and 13,326 base pairs, were then analyzed in the context of two previously-published near-complete sequences. Sequences revealed relatively well-conserved partial mitochondrial genomes which included complete sequences for 11 of 13 protein-coding genes, 16 of 23 tRNAs, and the large ribosomal subunit. Partial sequences were also recovered for cox1 and the small ribosomal subunit. Sequence analysis suggested that the cox2, nad5, and nad6 genes would be the best candidates for future population genetics analyses, due to their high number of variable sites. Future work to reveal the noncoding control region remains.

The mitochondrial genomes of Euphausia pacifica and Thysanoessa raschii sequenced using 454 next-generation sequencing, with a phylogenetic analysis of their position in the Malacostracan family tree.

Euphausiid krill play a critical role in coastal and oceanic food webs, linking primary producers to upper trophic levels. In addition, some species support commercial fisheries worldwide. Despite their ecological importance, the genetics of these important species remain poorly described. To improve our understanding of the genetics of these ecological links, we sequenced the mitochondrial genomes of two species of North Pacific krill, Euphausia pacifica and Thysanoessa raschii, using long-range PCR and 454 GS Junior next-generation sequencing technology. The E. pacifica mitogenome (14,692 + base pairs (bp)) encodes 13 protein-coding genes (PCGs), two ribosomal RNA (rRNA) genes, and at least 22 transfer RNA (tRNA) genes. The T. raschii mitogenome (14,240 + bp) encodes 13 PCGs, two rRNA genes, and at least 19 tRNA genes. The gene order in both species is similar to that of E. superba. Comparisons between Bering Sea and Yellow Sea E. pacifica revealed a total of 644 variable sites. The most variable protein-coding gene were atp8 (7.55 %, 12 of 159 sites variable), nad4 (6.35 %, 85 variable sites) and nad6 (6.32 %, 33 variable sites). Phylogenetic analyses to assess the phylogenetic position of the Euphausiacea, using the concatenated nucleic acid sequences of E. pacifica and T. raschii along with 46 previously published malacostracan mitogenomes, support the monophyly of the order Decapoda and indicate that the Euphausiacea share a common ancestor with the Decapoda. Future research should utilize this sequence data to explore the population genetics and molecular ecology of these species.

Reduced reproductive success of hatchery coho salmon in the wild: insights into most likely mechanisms.

Supplementation of wild salmonids with captive-bred fish is a common practice for both commercial and conservation purposes. However, evidence for lower fitness of captive-reared fish relative to wild fish has accumulated in recent years, diminishing the apparent effectiveness of supplementation as a management tool. To date, the mechanism(s) responsible for these fitness declines remain unknown. In this study, we showed with molecular parentage analysis that hatchery coho salmon (Oncorhynchus kisutch) had lower reproductive success than wild fish once they reproduced in the wild. This effect was more pronounced in males than in same-aged females. Hatchery spawned fish that were released as unfed fry (age 0), as well as hatchery fish raised for one year in the hatchery (released as smolts, age 1), both experienced lower lifetime reproductive success (RS) than wild fish. However, the subset of hatchery males that returned as 2-year olds (jacks) did not exhibit the same fitness decrease as males that returned as 3-year olds. Thus, we report three lines of evidence pointing to the absence of sexual selection in the hatchery as a contributing mechanism for fitness declines of hatchery fish in the wild: (i) hatchery fish released as unfed fry that survived to adulthood still had low RS relative to wild fish, (ii) age-3 male hatchery fish consistently showed a lower relative RS than female hatchery fish (suggesting a role for sexual selection), and (iii) age-2 jacks, which use a sneaker mating strategy, did not show the same declines as 3-year olds, which compete differently for females (again, implicating sexual selection).

Olfactory receptor related to class A, type 2 (V1r-like Ora2) genes are conserved between distantly related rockfishes (genus Sebastes).

V1r-like Ora genes express putative chemoreceptors that may function as pheromone receptors in fishes. We used a candidate gene approach to test whether V1r-like Ora2 genes show evidence of positive selection that could suggest a role in mate recognition and the avoidance of hybridization between closely related rockfishes. We amplified a 492-bp fragment of a single V1r-like Ora2 gene from each of 5 species of rockfish. Despite separation of up to 7.8 My, the sequence of V1r-like Ora2 is highly conserved. Genetic distances are small, and all our study species shared at least one sequence with another species. Sequence comparisons suggested that, although most amino acids were subject to purifying selection, 9 amino acids showed evidence of positive selection. Because many of these amino acids were not associated with the areas of the protein suggested to be involved in ligand binding based on structural similarity to other olfactory receptors, this signal may reflect an echo of the relaxation of selection associated with the speciation events that separate these species. Strong sequence conservation suggests that this gene is of functional significance. However, because of shared alleles among species, the V1r-like Ora2 gene, in isolation, would be unlikely to differentiate species during mating season.

A latitudinal cline in the Chinook salmon (Oncorhynchus tshawytscha) Clock gene: evidence for selection on PolyQ length variants.

A critical seasonal event for anadromous Chinook salmon (Oncorhynchus tshawytscha) is the time at which adults migrate from the ocean to breed in freshwater. We investigated whether allelic variation at the circadian rhythm genes, OtsClock1a and OtsClock1b, underlies genetic control of migration timing among 42 populations in North America. We identified eight length variants of the functionally important polyglutamine repeat motif (PolyQ) of OtsClock1b while OtsClock1a PolyQ was highly conserved. We found evidence of a latitudinal cline in average allele length and frequency of the two most common OtsClock1b alleles. The shorter 335 bp allele increases in frequency with decreasing latitude while the longer 359 bp allele increases in frequency at higher latitudes. Comparison to 13 microsatellite loci showed that 335 and 359 bp deviate significantly from neutral expectations. Furthermore, a hierarchical gene diversity analysis based on OtsClock1b PolyQ variation revealed that run timing explains 40.9 per cent of the overall genetic variance among populations. By contrast, an analysis based on 13 microsatellite loci showed that run timing explains only 13.2 per cent of the overall genetic variance. Our findings suggest that length polymorphisms in OtsClock1b PolyQ may be maintained by selection and reflect an adaptation to ecological factors correlated with latitude, such as the seasonally changing day length.

Providing Diverse Trainees an Early and Transparent Introduction to Academic Appointment and Promotion Processes.

Introduction: The growth in number of medical schools and increased numbers of faculty tracks have combined with evolving criteria for promotion to trigger a call for greater transparency of academic appointment and promotion processes. Most vulnerable to confusion about these changes are first-generation and diverse medical students and residents, the upstream pipeline of the academic medicine workforce. Diverse medical students have expressed diminished interest in academia because of perceived obstacles in appointment and promotion processes. Methods: This workshop was designed to utilize didactics and career reflection exercises to help trainees learn: (1) how to define core terms related to academic appointment and promotion processes, (2) how to compare data elements for different CVs and portfolios, (3) common steps in submitting a promotion package, and (4) that they can immediately begin to document content for academic CVs, portfolios, and promotion packages. Results: One hundred forty-five diverse participants completed an evaluation at eight conferences across the U.S. More than 90% strongly agreed or agreed that the aforementioned objectives were met. Participants commented that the workshop was "illuminating," was "very informative," and "provided an inside look of how faculty are evaluated." Results showed an immediate impact on participants' self-reported confidence to negotiate appointment and promotion processes. Discussion: Increases in self-rated confidence to negotiate appointment and promotion processes may help sustain trainees' interest in becoming future faculty. Further monitoring will be needed to determine if early exposure to these concepts improves probability of seeking, obtaining, and maintaining appointments.

Grandparentage assignments identify unexpected adfluvial life history tactic contributing offspring to a reintroduced population.

Diversity in life history tactics contributes to the persistence of a population because it helps to protect against stochastic environments by varying individuals in space and time. However, some life history tactics may not be accounted for when assessing the demographic viability of a population. One important factor in demographic viability assessments is cohort replacement rate (CRR), which is defined as the number of future adults produced by an adult. We assessed if precocial resident males (

Geo-Referenced, Abundance Calibrated Ocean Distribution of Chinook Salmon (Oncorhynchus tshawytscha) Stocks across the West Coast of North America.

Understanding seasonal migration and localized persistence of populations is critical for effective species harvest and conservation management. Pacific salmon (genus Oncorhynchus) forecasting models predict stock composition, abundance, and distribution during annual assessments of proposed fisheries impacts. Most models, however, fail to account for the influence of biophysical factors on year-to-year fluctuations in migratory distributions and stock-specific survival. In this study, the ocean distribution and relative abundance of Chinook salmon (O. tshawytscha) stocks encountered in the California Current large marine ecosystem, U.S.A were inferred using catch-per-unit effort (CPUE) fisheries and genetic stock identification data. In contrast to stock distributions estimated through coded-wire-tag recoveries (typically limited to hatchery salmon), stock-specific CPUE provides information for both wild and hatchery fish. Furthermore, in contrast to stock composition results, the stock-specific CPUE metric is independent of other stocks and is easily interpreted over multiple temporal or spatial scales. Tests for correlations between stock-specific CPUE and stock composition estimates revealed these measures diverged once proportional contributions of locally rare stocks were excluded from data sets. A novel aspect of this study was collection of data both in areas closed to commercial fisheries and during normal, open commercial fisheries. Because fishing fleet efficiency influences catch rates, we tested whether CPUE differed between closed area (non-retention) and open area (retention) data sets. A weak effect was indicated for some, but not all, analyzed cases. Novel visualizations produced from stock-specific CPUE-based ocean abundance facilitates consideration of how highly refined, spatial and genetic information could be incorporated in ocean fisheries management systems and for investigations of biogeographic factors that influence migratory distributions of fish.