Medusan Morphospace: Phylogenetic Constraints, Biomechanical Solutions, and Ecological Consequences

Medusae were the earliest animals to evolve muscle-powered swimming in the seas. Although medusae have achieved diverse and prominent ecological roles throughout the world\u27s oceans, we argue that the primitive organization of cnidarian muscle tissue limits force production and, hence, the mechanical alternatives for swimming bell function. We use a recently developed model comparing the potential force production with the hydrodynamic requirements of jet propulsion, and conclude that jet production is possible only at relatively small bell diameters. In contrast, production of a more complex wake via what we term rowing propulsion permits much larger sizes but requires a different suite of morphological features. Analysis of morphometric data from all medusan taxa independently confirms size-dependent patterns of bell forms that correspond with model predictions. Further, morphospace analysis indicates that various lineages within the Medusozoa have proceeded along either of two evolutionary trajectories. The first alternative involved restriction of jet-propelled medusan bell diameters to small dimensions. These medusae may be either solitary individuals (characteristic of Anthomedusae and Trachymedusae) or aggregates of small individual medusan units into larger colonial forms (characteristic of the nectophores of many members of the Siphonophorae). The second trajectory involved use of rowing propulsion (characteristic of Scyphozoa and some hydromedusan lineages such as the Leptomedusae and Narcomedusae) that allows much larger bell sizes. Convergence on either of the differing propulsive alternatives within the Medusozoa has emerged via parallel evolution among different medusan lineages. The distinctions between propulsive modes have important ecological ramifications because swimming and foraging are interdependent activities for medusae. Rowing swimmers are characteristically cruising predators that select different prey types from those selected by jet-propelled medusae, which are predominantly ambush predators. These relationships indicate that the different biomechanical solutions to constraints on bell function have entailed ecological consequences that are evident in the prey selection patterns and trophic impacts of contemporary medusan lineages

Isolation and Profiling of Circulating Tumorâ Associated Exosomes Using Extracellular Vesicular Lipidâ Protein Binding Affinity Based Microfluidic Device

Extracellular vesicles (EVs) are emerging as a potential diagnostic test for cancer. Owing to the recent advances in microfluidics, onâ chip EV isolation is showing promise with respect to improved recovery rates, smaller necessary sample volumes, and shorter processing times than ultracentrifugation. Immunoaffinityâ based microfluidic EV isolation using antiâ CD63 is widely used; however, antiâ CD63 is not specific to cancerâ EVs, and some cancers secrete EVs with low expression of CD63. Alternatively, phosphatidylserine (PS), usually expressed in the inner leaflet of the lipid bilayer of the cells, is shown to be expressed on the outer surface of cancerâ associated EVs. A new exosome isolation microfluidic device (newExoChip), conjugated with a PSâ specific protein, to isolate cancerâ associated exosomes from plasma, is presented. The device achieves 90% capture efficiency for cancer cell exosomes compared to 38% for healthy exosomes and isolates 35% more A549â derived exosomes than an antiâ CD63â conjugated device. Immobilized exosomes are then easily released using Ca2+ chelation. The recovered exosomes from clinical samples are characterized by electron microscopy and westernâ blot analysis, revealing exosomal shapes and exosomal protein expressions. The newExoChip facilitates the isolation of a specific subset of exosomes, allowing the exploration of the undiscovered roles of exosomes in cancer progression and metastasis.Onâ chip exosome isolation using immunoaffinity capture improves recovery from small sample volumes compared to ultracentrifugation. However, tetraspanins are not specific to cancer exosomes and some cancers secrete exosomes with low expression of tetraspanins. Here, a microfluidicâ device conjugated with proteins against phosphatidylserine (PS), shown to be expressed on the outer surface of cancerâ associated exosome, is used to isolate cancerâ associated exosomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/152534/1/smll201903600-sup-0001-SuppMat.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152534/2/smll201903600_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/152534/3/smll201903600.pd

Predator-Induced Vertical Behavior of a Ctenophore

Although many studies have focused on Mnemiopsis leidyi predation, little is known about the role of this ctenophore as prey when abundant in native and invaded pelagic systems. We examined the response of the ctenophore M. leidyi to the predatory ctenophore Beroe ovata in an experiment in which the two species could potentially sense each other while being physically separated. On average, M. leidyi responded to the predator’s presence by increasing variability in swimming speeds and by lowering their vertical distribution. Such behavior may help explain field records of vertical migration, as well as stratified and near-bottom distributions of M. leidyi

Application of pharmacogenomics and bioinformatics to exemplify the utility of human <i>ex vivo</i> organoculture models in the field of precision medicine

Here we describe a collaboration between industry, the National Health Service (NHS) and academia that sought to demonstrate how early understanding of both pharmacology and genomics can improve strategies for the development of precision medicines. Diseased tissue ethically acquired from patients suffering from chronic obstructive pulmonary disease (COPD), was used to investigate inter-patient variability in drug efficacy using ex vivo organocultures of fresh lung tissue as the test system. The reduction in inflammatory cytokines in the presence of various test drugs was used as the measure of drug efficacy and the individual patient responses were then matched against genotype and microRNA profiles in an attempt to identify unique predictors of drug responsiveness. Our findings suggest that genetic variation in CYP2E1 and SMAD3 genes may partly explain the observed variation in drug response

Population Maintenance of the Scyphozoan Cyanea sp. Settled Planulae and the Distribution of Medusae in the Niantic River, Connecticut, USA

Scyphozoan jellyfish are seasonally conspicuous in coastal waters, but relatively little is known about the factors that control their distribution and population dynamics.Cyanea sp is a seasonally abundant medusa in the Niantic River, Connecticut, U.S. and appears to maintain a population entirely within the estuary. To better understand the factors controlling their occurrence, we examined the temporal and spatial distribution of settled scyphistomae in relation to that of the medusae. Planula settlement patterns mirrored the presence of mature female medusae. The planulae settled primarily near the bottom. After settlement, planulacysts and polyps on the settlement plates were out competed by large barnacle and ascidian larvae, resulting in a sharp decline in cyst and polyp abundance. This stage-specific mortality may represent a population bottleneck in the life cycle of scyphozoans

Environmental Control of Phase Transition and Polyp Survival of a Massive-Outbreaker Jellyfish

A number of causes have been proposed to account for the occurrence of gelatinous zooplankton (both jellyfish and ctenophore) blooms. Jellyfish species have a complex life history involving a benthic asexual phase (polyp) and a pelagic sexual phase (medusa). Strong environmental control of jellyfish life cycles is suspected, but not fully understood. This study presents a comprehensive analysis on the physicochemical conditions that control the survival and phase transition of Cotylorhiza tuberculata; a scyphozoan that generates large outbreaks in the Mediterranean Sea. Laboratory experiments indicated that the influence of temperature on strobilation and polyp survival was the critical factor controlling the capacity of this species to proliferate. Early life stages were less sensitive to other factors such as salinity variations or the competitive advantage provided by zooxanthellae in a context of coastal eutrophication. Coherently with laboratory results, the presence/absence of outbreaks of this jellyfish in a particular year seems to be driven by temperature. This is the first time the environmental forcing of the mechanism driving the life cycle of a jellyfish has been disentangled via laboratory experimentation. Projecting this understanding to a field population under climatological variability results in a pattern coherent with in situ records

High throughput analysis of epistasis in genome-wide association studies with BiForce

Motivation: Gene–gene interactions (epistasis) are thought to be important in shaping complex traits, but they have been under-explored in genome-wide association studies (GWAS) due to the computational challenge of enumerating billions of single nucleotide polymorphism (SNP) combinations. Fast screening tools are needed to make epistasis analysis routinely available in GWAS. Results: We present BiForce to support high-throughput analysis of epistasis in GWAS for either quantitative or binary disease (case–control) traits. BiForce achieves great computational efficiency by using memory efficient data structures, Boolean bitwise operations and multithreaded parallelization. It performs a full pair-wise genome scan to detect interactions involving SNPs with or without significant marginal effects using appropriate Bonferroni-corrected significance thresholds. We show that BiForce is more powerful and significantly faster than published tools for both binary and quantitative traits in a series of performance tests on simulated and real datasets. We demonstrate BiForce in analysing eight metabolic traits in a GWAS cohort (323 697 SNPs, >4500 individuals) and two disease traits in another (>340 000 SNPs, >1750 cases and 1500 controls) on a 32-node computing cluster. BiForce completed analyses of the eight metabolic traits within 1 day, identified nine epistatic pairs of SNPs in five metabolic traits and 18 SNP pairs in two disease traits. BiForce can make the analysis of epistasis a routine exercise in GWAS and thus improve our understanding of the role of epistasis in the genetic regulation of complex traits. Availability and implementation: The software is free and can be downloaded from http://bioinfo.utu.fi/BiForce/. Contact: [email protected] Supplementary information: Supplementary data are available at Bioinformatics online

Arc requires PSD95 for assembly into postsynaptic complexes involved with neural dysfunction and intelligence

Arc is an activity-regulated neuronal protein, but little is known about its interactions, assembly into multiprotein complexes, and role in human disease and cognition. We applied an integrated proteomic and genetic strategy by targeting a tandem affinity purification (TAP) tag and Venus fluorescent protein into the endogenous Arc gene in mice. This allowed biochemical and proteomic characterization of native complexes in wild-type and knockout mice. We identified many Arc-interacting proteins, of which PSD95 was the most abundant. PSD95 was essential for Arc assembly into 1.5-MDa complexes and activity-dependent recruitment to excitatory synapses. Integrating human genetic data with proteomic data showed that Arc-PSD95 complexes are enriched in schizophrenia, intellectual disability, autism, and epilepsy mutations and normal variants in intelligence. We propose that Arc-PSD95 postsynaptic complexes potentially affect human cognitive function

Childhood asthma exacerbations and the Arg16 b2-receptor polymorphism: a meta-analysis stratified by treatment

Background: The Gly-to-Arg substitution at the 16 position (rs1042713) in the b2-adrenoceptor gene (ADRB2) is associated with enhanced downregulation and uncoupling of b2-receptors. Objectives: We sought to undertake a meta-analysis to test the hypothesis that there is an interaction between the A allele of rs1042713 (Arg16 amino acid) and long-acting b-agonist (LABA) exposure for asthma exacerbations in children. Methods: Children with diagnosed asthma were recruited in 5 populations (BREATHE, Genes-Environments and Admixture in Latino Americans II, PACMAN, the Paediatric Asthma Gene Environment Study, and the Pharmacogenetics of Adrenal Suppression with Inhaled Steroid Study). A history of recent exacerbation and asthma treatment was determined from questionnaire data. DNA was extracted, and the Gly16Arg genotype was determined. Results: Data from 4226 children of white Northern European and Latino origin were analyzed, and the odds ratio for exacerbation increased by 1.52 (95% CI, 1.17-1.99; P 5 .0021) for each copy of the A allele among the 637 children treated with inhaled corticosteroids (ICSs) plus LABAs but not for treatment with ICSs alone (n 5 1758) or ICSs plus leukotriene receptor antagonist (LTRAs; n 5 354) or ICSs plus LABAs plus LTRAs (n 5 569). Conclusions: The use of a LABA but not an LTRA as an ‘‘addon controller’’ is associated with increased risk of asthma exacerbation in children carrying 1 or 2 A alleles at rs1042713. Prospective genotype-stratified clinical trials are now required to explore the potential role of rs1042713 genotyping for personalized asthma therapy in children. (J Allergy Clin Immunol 201