Multiplexed base editing identifies functional gene-variant-context interactions.

Human genome sequencing efforts in healthy and diseased individuals continue to identify a broad spectrum of genetic variants associated with predisposition, progression, and therapeutic outcomes for diseases like cancer . Insights derived from these studies have significant potential to guide clinical diagnoses and treatment decisions; however, the relative importance and functional impact of most genetic variants remain poorly understood. Precision genome editing technologies like base and prime editing can be used to systematically engineer and interrogate diverse types of endogenous genetic variants in their native context .

[S1 guidelines for the management of postviral conditions using the example of post-COVID-19].

These S1 guidelines are an updated and expanded version of the S1 guidelines on long COVID differential diagnostic and management strategies. They summarize the state of knowledge on postviral conditions like long/post COVID at the time of writing. Due to the dynamic nature of knowledge development, they are intended to be "living guidelines".

Characterization of the phenotype in .

In the early 20th century, Calvin Bridges and Thomas Morgan identified a number of spontaneous mutations that displayed visible phenotypes in adult flies and subsequent analysis of these mutations over the past century have provided fundamental insights into subdisciplines of biology such as genetics, developmental, and cell biology. One of the mutations they identified in 1915 was named ( ) and was described by Bridges and Morgan as having two visible phenotype characteristics in the wing. The wings were "held out at a wider angle from the body" and had a break in wing vein L3.

MCB-613 exploits a collateral sensitivity in drug resistant -mutant non-small cell lung cancer through covalent inhibition of KEAP1.

Targeted therapies have revolutionized cancer chemotherapy. Unfortunately, most patients develop multifocal resistance to these drugs within a matter of months. Here, we used a high-throughput phenotypic small molecule screen to identify MCB-613 as a compound that selectively targets -mutant, EGFR inhibitor-resistant non-small cell lung cancer (NSCLC) cells harboring diverse resistance mechanisms.

Vertical space use and thermal range of the great hammerhead (Sphyrna mokarran), (Rüppell, 1837) in the western North Atlantic.

The great hammerhead (Sphyrna mokarran) is a highly mobile, large-bodied shark primarily found in coastal-pelagic and semi-oceanic waters across a circumtropical range. It is a target or by-catch species in multiple fisheries, and as a result, rapid population declines have occurred in many regions. These declines have contributed to the species being assessed as globally critically endangered on the IUCN Red List.

Age group DNA methylation differences in lemon sharks (): Implications for future age estimation tools.

Age information is often non-existent for most shark populations due to a lack of measurable physiological and morphological traits that can be used to estimate age. Recently, epigenetic clocks have been found to accurately estimate age for mammals, birds, and fish. However, since these clocks rely, among other things, on the availability of reference genomes, their application is hampered in non-traditional model organisms lacking such molecular resources.

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.

Personality-driven life history trade-offs differ in two subpopulations of free-ranging predators.

Consistent individual differences in behaviour (i.e. personality) can be explained in an evolutionary context if they are favoured by life history trade-offs as conceptualized in the pace-of-life syndrome (POLS) hypothesis.

Plant-animal interactions between carnivorous plants, sheet-web spiders, and ground-running spiders as guild predators in a wet meadow community.

Plant-animal interactions are diverse and widespread shaping ecology, evolution, and biodiversity of most ecological communities. Carnivorous plants are unusual in that they can be simultaneously engaged with animals in multiple mutualistic and antagonistic interactions including reversed plant-animal interactions where they are the predator. Competition with animals is a potential antagonistic plant-animal interaction unique to carnivorous plants when they and animal predators consume the same prey.

No apparent negative tagging effects after 13 years at liberty for lemon shark, Negaprion brevirostris implanted with acoustic transmitter.

An intact and uncompromised internal acoustic transmitter was non-lethally recovered from a lemon shark Negaprion brevirostris, after 13 years at liberty. The shark, first tagged at an estimated age of 2 years old near South Bimini, Bahamas in 2004, was recaptured in 2017 with a total length of 264 cm. The tagged shark displayed typical growth rate, pregnancy, natal homing and pupping behaviour of other individuals in this population.

Risky business for a juvenile marine predator? Testing the influence of foraging strategies on size and growth rate under natural conditions.

Mechanisms driving selection of body size and growth rate in wild marine vertebrates are poorly understood, thus limiting knowledge of their fitness costs at ecological, physiological and genetic scales. Here, we indirectly tested whether selection for size-related traits of juvenile sharks that inhabit a nursery hosting two dichotomous habitats, protected mangroves (low predation risk) and exposed seagrass beds (high predation risk), is influenced by their foraging behaviour. Juvenile sharks displayed a continuum of foraging strategies between mangrove and seagrass areas, with some individuals preferentially feeding in one habitat over another.

Modeling the population dynamics of lemon sharks.

Background: Long-lived marine megavertebrates (e.g. sharks, turtles, mammals, and seabirds) are inherently vulnerable to anthropogenic mortality.

Regional-scale migrations and habitat use of juvenile lemon sharks (Negaprion brevirostris) in the US South Atlantic.

Resolving the geographic extent and timing of coastal shark migrations, as well as their environmental cues, is essential for refining shark management strategies in anticipation of increasing anthropogenic stressors to coastal ecosystems. We employed a regional-scale passive acoustic telemetry array encompassing 300 km of the east Florida coast to assess what factors influence site fidelity of juvenile lemon sharks (Negaprion brevirostris) to an exposed coastal nursery at Cape Canaveral, and to document the timing and rate of their seasonal migrations. Movements of 54 juvenile lemon sharks were monitored for three years with individuals tracked for up to 751 days.

Two decades of genetic profiling yields first evidence of natal philopatry and long-term fidelity to parturition sites in sharks.

Sharks are a globally threatened group of marine fishes that often breed in their natal region of origin. There has even been speculation that female sharks return to their exact birthplace to breed ('natal philopatry'), which would have important conservation implications. Genetic profiling of lemon sharks (Negaprion brevirostris) from 20 consecutive cohorts (1993-2012) at Bimini, Bahamas, showed that certain females faithfully gave birth at this site for nearly two decades.

Monogenoid infection of neonatal and older juvenile lemon sharks, Negaprion brevirostris (Carcharhinidae), in a shark nursery.

Fifty lemon sharks, Negaprion brevirostris , were captured in a shallow, mangrove-fringed shark nursery at Bimini, Bahamas and examined for the presence of skin-dwelling ectoparasitic monogenoids (Monogenoidea). Sixteen sharks were infected by Dermophthirius nigrellii (Microbothriidae); the youngest host was estimated to be 3- to 4-wk-old. Infection prevalence, mean intensity, and median intensity (0.

Social learning in juvenile lemon sharks, Negaprion brevirostris.

Social learning is taxonomically widespread and can provide distinct behavioural advantages, such as in finding food or avoiding predators more efficiently. Although extensively studied in bony fishes, no such empirical evidence exists for cartilaginous fishes. Our aim in this study was to experimentally investigate the social learning capabilities of juvenile lemon sharks, Negaprion brevirostris.

Anthropogenic disturbance and evolutionary parameters: a lemon shark population experiencing habitat loss.

The level of genetic variation in natural populations influences evolutionary potential, and may therefore influence responses to selection in the face of future environmental changes. By combining long-term monitoring of marked individuals with genetic pedigree reconstruction, we assessed whether habitat loss influenced genetic variation in a lemon shark (Negaprion brevirostris) population at an isolated nursery lagoon (Bimini, Bahamas). We also tracked changes in the strength and direction of natural selection.

Novel acoustic technology for studying free-ranging shark social behaviour by recording individuals' interactions.

Group behaviours are widespread among fish but comparatively little is known about the interactions between free-ranging individuals and how these might change across different spatio-temporal scales. This is largely due to the difficulty of observing wild fish groups directly underwater over long enough time periods to quantify group structure and individual associations. Here we describe the use of a novel technology, an animal-borne acoustic proximity receiver that records close-spatial associations between free-ranging fish by detection of acoustic signals emitted from transmitters on other individuals.

Long-term natal site-fidelity by immature lemon sharks (Negaprion brevirostris) at a subtropical island.

Although many sharks begin their life confined in nursery habitats, it is unknown how rapidly they disperse away from their natal area once they leave the nursery. We examine this issue in immature lemon sharks (Negaprion brevirostris) from the time they leave the nursery (approximately age 3) at a subtropical island (Bimini, Bahamas), through to the onset of sexual maturity (approximately age 12). From 1995 to 2007 we tagged and genotyped a large fraction of the nursery-bound sharks at this location (0-3 years of age, N = 1776 individuals).

Evolutionary potential of a large marine vertebrate: quantitative genetic parameters in a wild population.

Estimating quantitative genetic parameters ideally takes place in natural populations, but relatively few studies have overcome the inherent logistical difficulties. For this reason, no estimates currently exist for the genetic basis of life-history traits in natural populations of large marine vertebrates. And yet such estimates are likely to be important given the exposure of this taxon to changing selection pressures, and the relevance of life-history traits to population productivity.

A genetic assessment of polyandry and breeding-site fidelity in lemon sharks.

We here employ 11 microsatellite markers and recently developed litter reconstruction methods to infer mating system parameters (i.e. polyandry and breeding-site fidelity) at a lemon shark nursery site in Marquesas Key, Florida.

Are indirect genetic benefits associated with polyandry? Testing predictions in a natural population of lemon sharks.

Multiple mating has clear fitness benefits for males, but uncertain benefits and costs for females. We tested for indirect genetic benefits of polyandry in a natural population, by using data from a long-term genetic and demographic study of lemon sharks (Negaprion brevirostris) at Bimini, Bahamas. To do so, we followed the fates of individuals from six cohorts (450 age-0 and 254 age-1 fish) in relation to their individual level of genetic variation, and whether they were from polyandrous or monoandrous litters.

Reconstruction of parental microsatellite genotypes reveals female polyandry and philopatry in the lemon shark, Negaprion brevirostris.

Because sharks possess an unusual suite of reproductive characteristics, including internal fertilization, sperm storage, relatively low fecundity, and reproductive modes that range from oviparity to viviparity, they can provide important insight into the evolution of mating systems and sexual selection. Yet, to date, few studies have characterized behavioral and genetic mating systems in natural populations of sharks or other elasmobranchs. In this study, highly polymorphic microsatellite loci were used to examine breeding biology of a large coastal shark, the lemon shark, Negaprion brevirostris, at a tropical lagoon nursery.