PAX3-FOXO1 dictates myogenic reprogramming and rhabdomyosarcoma identity in endothelial progenitors.

Fusion-positive rhabdomyosarcoma (FP-RMS) driven by the expression of the PAX3-FOXO1 (P3F) fusion oncoprotein is an aggressive subtype of pediatric rhabdomyosarcoma. FP-RMS histologically resembles developing muscle yet occurs throughout the body in areas devoid of skeletal muscle highlighting that FP-RMS is not derived from an exclusively myogenic cell of origin. Here we demonstrate that P3F reprograms mouse and human endothelial progenitors to FP-RMS. We show that P3F expression in aP2-Cre expressing cells reprograms endothelial progenitors to functional myogenic stem cells capable of regenerating injured muscle fibers. Further, we describe a FP-RMS mouse model driven by P3F expression and Cdkn2a loss in endothelial cells. Additionally, we show that P3F expression in TP53-null human iPSCs blocks endothelial-directed differentiation and guides cells to become myogenic cells that form FP-RMS tumors in immunocompromised mice. Together these findings demonstrate that FP-RMS can originate from aberrant development of non-myogenic cells driven by P3F.

Eastern oysters Crassostrea virginica settle near inlets in a lagoonal estuary: spatial and temporal distribution of recruitment in Mid-Atlantic Coastal Bays (Maryland, USA).

Background: Declines of the Eastern oyster, Crassostrea virginica, and its numerous ecological benefits have spurred oyster restoration initiatives. Successful restoration of a self-sustaining oyster population requires evaluating the temporal and spatial patterns of recruitment (settlement and survival) of oyster larvae in the target waterbody. Restoration of the Eastern oyster population in the Maryland Coastal Bays (MCBs), USA, a shallow lagoonal estuary, is of interest to federal, state, and non-governmental, but the location and timing of natural recruitment is not known. Methods: We assessed the spatial and temporal variation in oyster larval recruitment throughout the MCBs using horizontal ceramic tiles and PVC plates. Newly settled oyster larvae (recruits) were monitored biweekly from June to September 2019 and 2020 at 12 sites in the MCBs and a comparison site in Wachapreague, Virginia. Water quality measurements collected included temperature, salinity, dissolved oxygen, pH, and turbidity. The objectives of this study were to determine (1) the most effective substrate and design for monitoring oyster recruitment, (2) the spatial and temporal distribution of oyster larval recruitment in the MCBs, and (3) patterns in oyster larval recruitment that would be applicable to other lagoonal estuaries. Results: (1) Ceramic tiles were more effective than PVC plates for recruiting oyster larvae. (2) Peak settlement began during the period from late June through July, and oyster recruitment was greatest at sites closest to the Ocean City and Chincoteague inlets. (3) Areas near broodstock that have slow flushing rates to retain larvae may provide the best environments for recruitment of oysters to lagoonal estuaries. Discussion: As the first study on oyster larval recruitment in the MCBs, our results provide insight into their spatial and temporal distribution, methods that can serve as a foundation for future recruitment studies in other lagoonal estuaries, and baseline data that can be used to inform stakeholders and evaluate the success of oyster restoration projects in MCBs.

Cystargolide-based amide and ester Pz analogues as proteasome inhibitors and anti-cancer agents.

A series of cystargolide-based ß-lactone analogues containing nitrogen atoms at the Pz portion of the scaffold were prepared and evaluated as proteasome inhibitors, and for their cytotoxicity profile toward several cancer cell lines. Inclusion of one, two or even three nitrogen atoms at the Pz portion of the cystargolide scaffold is well tolerated, producing analogues with low nanomolar proteasome inhibition activity, in many cases superior to carfilzomib. Additionally, analogue 8g, containing an ester and pyrazine group at Pz, was shown to possess significant activity toward RPMI 8226 cells (IC50 = 21 nM) and to be less cytotoxic toward the normal tissue model MCF10A cells than carfilzomib.

Impairment indicators for predicting delayed mortality in black sea bass (Centropristis striata) discards within the commercial trap fishery.

Harvest restrictions (e.g. size, sex or species limitations) that are implemented to maintain sustainable fisheries often result in by-catch, e.g. unwanted non-target catch. By-catch is frequently discarded back into the ocean and assumed to survive. However, discarded fishes can succumb to delayed mortality resulting from accumulated stress from fishing activity, and such mortality can impede sustainability efforts. Quantifying reflex and behavioural impairments is a quick and cost-effective method to predict discard-related mortality in some species. We developed and evaluated the effectiveness of a release condition index, based on a reflex-action mortality prediction (RAMP) model, for predicting delayed mortality of black sea bass (Centropristis striata) caught and discarded by the commercial trap fishery in the Mid-Atlantic Bight. Accumulation of impairments, and therefore release condition index, was strongly correlated with delayed mortality of black sea bass discarded and held in sea cages. This is the first release condition index validation study to predict mortality in black sea bass and could be a useful approach for predicting delayed mortality in the commercial fishery.

Sea whip coral Leptogorgia virgulata in the Mid-Atlantic Bight: Colony complexity, age, and growth.

Sea whip coral Leptogorgia virgulata are a common structural component of both natural and artificial hard-bottom reef habitats in the mid-Atlantic region and may serve as essential habitat for commercially valuable species. However, they are slow-growing, easily damaged, and especially vulnerable to damage by passive fishing gear such as pots and traps. Despite their potential importance, until recently, sea whips have been generally understudied in this region. We examined the colony complexity, length, age, and growth of sea whips from four artificial reef sites in the mid-Atlantic region to gain a better understanding of their biology in the area. There were no significant differences in the bifurcation (Rb) and tributary to source (T/S) ratios between sites, with the Rb ≈3 for all sites, indicating similar complexity between sites. The total length distribution was 8.3 cm to 85.3 cm, and 50% of corals in the range of 34.2-56.4 cm. Age, estimated from annual growth ring counts, ranged from 2 to 15 y, with 50% of corals in the range of 6 to 8 y. The large proportion of middle-sized and middle-aged corals suggests episodic recruitment. Age-length keys showed the trend of age increasing with total coral length, and a von Bertalanffy growth model demonstrated size-dependent growth following the equation: E[L-t] (cm) = 86.1(1-e-0.14(t-1.44)). This is the first study providing such data for sea whips in the coastal mid-Atlantic region, and the baseline created will be a useful reference to study changes over time.

The relationship between fish abundance and benthic community structure on artificial reefs in the Mid-Atlantic Bight, and the importance of sea whip corals Leptogorgia virgulata.

Autogenic engineers (i.e., biogenic structure) add to habitat complexity by altering the environment by their own physical structures. The presence of autogenic engineers is correlated with increases in species abundance and biodiversity. Biogenic structural communities off the coast of Delaware, Maryland, and Virginia (Delmarva) are comprised of multiple species including boring sponge Cliona celata, various hydroids (i.e., Tubularia sp., Obelia sp., Campanular sp.), northern stone coral Astrangia poculata, sea whips Leptogorgia virgulata, and blue mussels Mytilus edulis. Sea whips are soft corals that provide the majority of vertical height to benthic structure off the coast of the Delmarva peninsula. The mid-Atlantic bight is inhabited by several economically valuable fishes; however, data regarding habitat composition, habitat quality, and fish abundance are scarce. We collected quadrat and sea whip images from 12 artificial reef sites (i.e., shipwrecks) ranging from 10 to 24 m depth to determine proportional coverage of biogenic structures and to assess habitat health, respectively. Underwater video surveys were used to estimate fish abundances on the 12 study sites and determine if fish abundance was related to biogenic coverage and habitat health. Our results showed that higher fish abundance was significantly correlated with higher proportional sea whip coral coverage, but showed no significant relationship to other biogenic structure. Assessment of sea whip condition (as a damage index) showed that sea whip corals on artificial reefs off the Delmarva coast exhibited minor signs of degradation that did not differ significantly among study sites.

Characterizing the benthic community in Maryland's offshore wind energy areas using a towed camera sled: Developing a method to reduce the effort of image analysis and community description.

Offshore wind farms are a crucial component for the improvement of renewable energy in the United States. The Bureau of Ocean Energy Management (BOEM) designated ~170 km2 of shelf area for wind energy development off the coast of Maryland, USA. In order to understand potential environmental impacts of wind turbine installation on the benthic ecosystem within the designated area, we conducted a study to visually characterize bottom habitats and epibenthic communities in the Mid-Atlantic Outer Continental Shelf blocks of the Maryland wind energy area. Seven 5 km long transects were sampled using a towed camera sled with a downward-facing digital camera that captured images at 5 frames·s-1s. Additional small-mesh beam trawling was also conducted at selected locations complementary for species identification. Image data were analyzed using two image selection methods, random and systematic (i.e. video frames were selected at various intervals). For both methods, estimates of community diversity (Hill's N2) stabilized with sample sizes ranging from 316 to 398 frames. Our results allowed us to define distinct epibenthic communities and bottom habitats that are associated with offshore wind energy sites and to develop a sampling technique for digital images that can be applied to other research programs.

Cost of education and earning potential for non-physician anesthesia providers.

Potential non-physician anesthesia students gauge many different aspects of a graduate program prior to applying, but cost of education and earning potential are typically high priorities for students. Our analysis evaluated the cost of tuition for all certified registered nurse anesthetist (CRNA) and anesthesiologist assistant (AA) programs in the United States, as well as earning potential for both professions. We collected educational cost data from school websites and salary data from the Medical Group Management Association's Physician Compensation and Production Survey: 2012 Report in order to compare the two groups. We found that the median cost of public CRNA programs is $40,195 and the median cost of private programs is $60,941, with an overall median of $51,720. Mean compensation for CRNAs in 2011 was $156,642. The median cost of public AA programs is $68,210 compared with $77,155 for private AA education, and an overall median cost of $76,037. Average compensation for AAs in 2011 was $123,328. Considering these factors, nurse anesthesia school is a better choice for candidates who already possess a nursing license; however, for those prospective students who are not nurses, AA school may be a more economical choice, depending on the type and location of practice desired.

Bait and the susceptibility of American lobsters Homarus americanus to epizootic shell disease.

Shell disease (SD) has been observed in lobster populations for almost a hundred years, but recently, rates of an epizootic form of shell disease (ESD) have increased in the southern New England (USA) area. A large proportion of fish in the diet of American lobsters Homarus americanus has been linked to increased rates of SD. Therefore, the use of fish as lobster bait may be linked to increased ESD rates in lobsters. Lobsters from the western portion of Martha's Vineyard, MA (41 degrees N, 71 degrees W), were randomly divided into 3 groups of 16 and exposed to dietary treatments (100% herring; 48% crab, 48% blue mussel and 4% plant matter; or 50% herring, 24% crab, 24% mussel, 2% plant matter) to determine if lobster tissue delta15N levels reflected diet. The results of the feeding experiment confirmed that differences in diet are observed in the delta15N levels of lobster muscle tissue. The delta15N levels of tissue samples from 175 wild lobsters with varying degrees of ESD were unrelated to ESD severity but did indicate lobsters were eating large amounts of fish (bait). This result does not support the speculation that fish used as bait is contributing to ESD outbreaks in portions of the southern New England area.

Effects of epizootic shell disease in American lobster Homarus americanus determined using a quantitative disease index.

The incidence of epizootic shell disease in American lobster Homarus americanus has increased in southern New England, U.S.A., in the last decade, but few longitudinal studies have followed the disease progress in individual lobsters or demonstrated direct effects on mortality or growth. Diseased lobsters were held in the laboratory for 1 yr, and the progression of disease and its effects on molting, mortality, and growth were monitored. A quantitative disease index (QDI) was developed by measuring disease lesions in digital images of the carapace and expressing the result as a proportion of shell area. Some lobsters died due to high temperatures, but at least 13 of 55 lobsters (24%) died as a direct result of disease-related problems, mostly during molting, and there was a significant relationship between mortality and high values of the QDI. Lobsters that molted successfully were free of disease lesions, but many had exoskeletal deformities. There was no relationship between pre-molt size and disease severity, but molt increment was significantly correlated with premolt carapace length (CL) and negatively correlated with QDI. However, percentage growth was negatively correlated with QDI, but not with pre-molt CL. These significant lethal and sublethal effects of epizootic shell disease should be considered in lobster management.

Una investigación transnacional sobre la disponibilidad de armas de fuego y la violencia letal

En una investigación transversal realizada sobre 14 países, se estableció una relación muy significativa entre la proporción de hogares en los que hay armas de fuego y la proporción de suicidios cometidos con ellas. No obstante, no hay muchas pruebas estadísticas que demuestren la existencia de una asociación entre el fácil acceso a las armas de fuego y el homicidio. (AU)