The Role of SRSF3 in Control of Alternative Splicing of CPEB2 in Triple Negative Breast Cancer

In the presented study, we identified that SRSF3 controls the alternative splicing of CPEB2 and consequently promotes a metastatic phenotype in triple negative breast cancer (TNBC). TNBC causes thousands of deaths annually, frequently due to a lack of effective treatments and a high rate of metastasis in patients. Alternative splicing has been found to be dysregulated in numerous cancers, while splicing factors such as SRSF3 are variably expressed. In this study we performed a siRNA panel to screen potential splicing factors, then used specific siRNA to study the effect of its knockdown on cellular function. These results showed that SRSF3 encourages the production of the pro-metastatic isoform of CPEB2, which contributes the aggressive phenotype of the tumor. We utilized numerous methods to measure the metastatic function of cultured TNBC cells to determine if SRSF3 strongly promoted the metastatic function. These data showed that siRNA reduction of SRSF3 was able to reduce the metastatic potential of cancer cells. These findings suggest that SRSF3 has great potential as a therapeutic measure to reduce and minimize the aggressiveness of TNBC tumors

Using Performance Assessments to Connect Fractions and Rational Expressions: Noyce Scholars as Mentors to Pre-Service Elementary Teachers

At Georgia Southern University, Noyce scholars are not only being mentored, but they are also serving as mentors to preservice elementary teachers. One topic that proves to be problematic for many students is the conceptual understanding of fractions and rational expressions. Since our Noyce scholars with mathematics degrees will be teaching algebra, it is important that they are fluent with the arithmetic to algebra connection. In addition, it is crucial that these mathematics majors become stakeholders in mathematics education at the elementary school level. Performance assessments can provide the structure necessary for assisting pre-service elementary teachers in firmly establishing the arithmetic to algebra connection. This session showcases a performance assessment where students are not only required to connect concrete models with standard fraction algorithms, but are also required to explain these connections. In this performance assessment, fraction bars are used with the number line in order to establish the arithmetic to algebra connection. Noyce scholars assist by helping and evaluating these pre-service teachers. By participating, not only do Noyce scholars support elementary teachers, but they also gain strategies and resources needed to teach fractions in a way that leads to conceptual understanding

Patterns of normal transvalvular regurgitation in mechanical valve prostheses

AbstractThe magnitude and spatial distribution of normal leakage through mechanical prosthetic valves were studied in an in vitro model of mitral regurgitation. The effective regurgitant orifice was calculated from regurgitant rate at different transvalvular pressure differences and flow velocities. This effective orifice area was 0.6 to 2 mm2for three tilting disc prostheses (Medtronic-Hall sizes 21, 25 and 29) and 0.2 to 1.1 mm2for three bileaflet valves (St. Jude Medical sizes 21, 25 and 33).In the single disc valves, Doppler color flow examination disclosed a prominent central regurgitant jet around the central hole for the strut, accompanied by minor leakage along the rim of the disc (central to peripheral jet area ratio 3.3 ± 1.2). The bileaflet prostheses showed a peculiar complex pattern: in planes parallel to the two disc axes, convergent peripherally arising jets were visualized, whereas in orthogonal planes several diverging jets were seen.Mounting the disc and bileaflet valves on a water-filled tube allowed reproduction and interpretation of this pattern: for the bileaflet valve, the jets originated predominantly from valve ring protrusions that contained the axis hinge points and created a converging V pattern in planes parallel to the leaflets and a diverging V pattern in orthogonal planes.Similar patterns were observed during transesophageal echocardiography in 20 patients with a normally functioning St. Jude prosthesis. In 10 patients with a Medtronic-Hall valve, a dominant central jet was observed with one or more smaller peripheral jets. The median central to peripheral jet area ratio was 5 to 1.In summary, in two types of mechanical valve prostheses, effective leakage orifice areas are reported and criteria proposed for the differentiation of “physiologic” and pathologic regurgitation based on the spatial configuration of the jets

First Account of Phylogeographic Variation, Larval Characters, and Laboratory Rearing of the Endangered Cobblestone Tiger Beetle Cicindelidia marginipennis, Dejean, 1831 with Observations of Their Natural History

The cobblestone tiger beetle, Cicindelidia marginipennis (Dejean, 1831) is a North American species specializing in riparian habitats from New Brunswick, Canada, to Alabama in the United States. In the United States, this species is state-listed as threatened or endangered range-wide and periodically receives consideration for federal listing, mostly due to habitat decline. Despite its conservation status, intraspecific genetic diversity for this species has not been explored and little is known about its natural history. To support further inquiry into the biology of C. marginipennis, this study provides the first look at range-wide genetic diversity using mitochondrial DNA (mtDNA), describes all three larval instars, and describes natural history characteristics from captive rearing and field observation. Based on mtDNA analyses, our results suggest that geographically based population structure may exist throughout the range, with individuals from Alabama possessing haplotypes not found elsewhere in our sampling. Further genetic analyses, particularly multi-locus analyses, are needed to determine whether the Alabama population represents a separate cryptic species. Our morphological analysis and descriptions of larval instars reveal a combination of characteristics that can be used to differentiate C. marginipennis from closely related and co-occurring species. Based on our field observations, we find that the larval “throw pile” of soil excavated from burrows is a key search image for locating larvae, and we provide descriptions and detailed photographs to aid surveys. Lastly, we find that this species can be successfully reared in captivity and provide guidelines to aid future recovery efforts

Translational control of recombinant human acetylcholinesterase accumulation in plants

<p>Abstract</p> <p>Background</p> <p>Codon usage differences are known to regulate the levels of gene expression in a species-specific manner, with the primary factors often cited to be mRNA processing and accumulation. We have challenged this conclusion by expressing the human acetylcholinesterase coding sequence in transgenic plants in its native GC-rich sequence and compared to a matched sequence with (dicotyledonous) plant-optimized codon usage and a lower GC content.</p> <p>Results</p> <p>We demonstrate a 5 to 10 fold increase in accumulation levels of the "synaptic" splice variant of human acetylcholinesterase in <it>Nicotiana benthamiana </it>plants expressing the optimized gene as compared to the native human sequence. Both transient expression assays and stable transformants demonstrated conspicuously increased accumulation levels. Importantly, we find that the increase is not a result of increased levels of acetylcholinesterase mRNA, but rather its facilitated translation, possibly due to the reduced energy required to unfold the sequence-optimized mRNA.</p> <p>Conclusion</p> <p>Our findings demonstrate that codon usage differences may regulate gene expression at different levels and anticipate translational control of acetylcholinesterase gene expression in its native mammalian host as well.</p

Left ventricular function after valve repair for chronic mitral regurgitation: Predictive value of preoperative assessment of contractile reserve by exercise echocardiography

Objectives.We evaluated the value of preoperative assessment of left ventricular contractile reserve in predicting ventricular function after valve repair for minimally symptomatic mitral regurgitation.Background.The optimal timing for operation in minimally symptomatic patients with significant mitral regurgitation is controversial. Accurate preoperative assessment of left ventricular function is difficult, and the ability to predict postoperative function is limited. Previous studies in patients undergoing mitral valve replacement may not be applicable in the present era of valve repair.Methods.We performed exercise echocardiography in 139 patients with isolated mitral regurgitation and no coronary disease, 74 of whom subsequently underwent uncomplicated valve repair. We measured rest left ventricular end-systolic dimension, end-systolic wall stress and positive first derivative of left ventricular pressure (dP/dt). End-diastolic and end-systolic volumes and ejection fraction were measured preoperatively at rest, immediately after exercise and postoperatively.Results.Ejection fraction decreased postoperatively to 55 ± 10% from a rest preoperative value of 64 ± 9% (p < 0.001). Compared with patients with a postoperative ejection fraction ≥50% (n = 56), patients with postoperative ejection fraction <50% (n = 18) had a significantly lower preoperative exercise ejection fraction (57 ± 11% vs. 73 ± 9%, p < 0.0005), a larger exercise end-systolic volume index (32 ± 8 vs. 18 ± 7 cm3/m2, p < 0.0005) and a lower change in ejection fraction with exercise (−4 ± 8% vs. 9 ± 10%, p < 0.005). Preoperative rest indexes, including dP/dt, end-systolic wall stress and end-systolic volume index were less predictive, whereas exercise capacity, rest ejection fraction and end-systolic dimension were not predictive of postrepair ejection fraction. An exercise end-systolic volume index >25 cm3/m2 was the best predictor of postoperative dysfunction, with a sensitivity and specificity of 83%.Conclusions.In minimally symptomatic patients with mitral regurgitation, latent ventricular dysfunction may be indicated by a limited contractile reserve, manifest at exercise as an inadequate increase in ejection fraction and a larger end-systolic volume. These variables may also be used to predict left ventricular function after repair

Prognostic Value of RV Function Before and After Lung Transplantation

AbstractObjectivesWe investigated the effects of lung transplantation on right ventricular (RV) function as well as the prognostic value of pre- and post-transplantation RV function.BackgroundAlthough lung transplantation success has improved over recent decades, outcomes remain a challenge. Identifying predictors of mortality in lung transplant recipients may lead to improved long-term outcomes after lung transplantation.MethodsEighty-nine (age 60 ± 6 years, 58 men) consecutive patients who underwent single or double lung transplantation and had pre- and post-transplantation echocardiograms between July 2001 and August 2012 were evaluated. Echocardiographic measurements were performed before and after lung transplantation. Left ventricular (LV) and RV longitudinal strains were analyzed using velocity vector imaging. Cox proportional prognostic hazard models predicting all-cause death were built.ResultsThere were 46 all-cause (52%) and 17 cardiac (19%) deaths during 43 ± 33 months of follow-up. After lung transplantation, echocardiography showed improved systolic pulmonary artery pressure (SPAP) (50 ± 19 mm Hg to 40 ± 13 mm Hg) and RV strain (−17 ± 5% to −18 ± 4%). No pre-transplantation RV parameter predicted all-cause mortality. After adjustment for age, sex, surgery type, and etiology of lung disease in a Cox proportional hazards model, both post-transplantation RV strain (hazard ratio: 1.13, 95% confidence interval: 1.04 to 1.23, p = 0.005), and post-transplantation SPAP (hazard ratio: 1.03, 95% confidence interval: 1.01 to 1.05, p = 0.011) were independent predictors of all-cause mortality. When post-transplantation RV strain and post-transplantation SPAP were added the clinical predictive model based on age, sex, surgery type, and etiology, the C-statistic improves from 0.60 to 0.80 (p = 0.002).ConclusionsAlterations of RV function and pulmonary artery pressure normalize, and post-transplantation RV function may provide prognostic data in patients after lung transplantation. Our study is based on a highly and retrospectively selected group. We believe that larger prospective studies are warranted to confirm this result

Space Use and Relative Habitat Selection for Immature Green Turtles Within a Caribbean Marine Protected Area

Background A better understanding of sea turtle spatial ecology is critical for the continued conservation of imperiled sea turtles and their habitats. For resource managers to develop the most effective conservation strategies, it is especially important to examine how turtles use and select for habitats within their developmental foraging grounds. Here, we examine the space use and relative habitat selection of immature green turtles (Chelonia mydas) using acoustic telemetry within the marine protected area, Buck Island Reef National Monument (BIRNM), St. Croix, United States Virgin Islands. Results Space use by turtles was concentrated on the southern side of Buck Island, but also extended to the northeast and northwest areas of the island, as indicated by minimum convex polygons (MCPs) and 99%, 95%, and 50% kernel density estimations (KDEs). On average space use for all categories was \u3c 3 km2 with mean KDE area overlap ranging from 41.9 to 67.7%. Cumulative monthly MCPs and their proportions to full MCPs began to stabilize 3 to 6 detection months after release, respectively. Resource selection functions (RSFs) were implemented using a generalized linear mixed effects model with turtle ID as the random effect. After model selection, the accuracy of the top model was 77.3% and showed relative habitat selection values were highest at shallow depths, for areas in close proximity to seagrass, and in reef zones for both day and night, and within lagoon zones at night. The top model was also extended to predict across BIRNM at both day and night. Conclusion More traditional acoustic telemetry analyses in combination with RSFs provide novel insights into animal space use and relative resource selection. Here, we demonstrated immature green turtles within the BIRNM have small, specific home ranges and core use areas with temporally varying relative selection strengths across habitat types. We conclude the BIRNM marine protected area is providing sufficient protection for immature green turtles, however, habitat protection could be focused in both areas of high space use and in locations where high relative selection values were determined. Ultimately, the methodologies and results presented here may help to design strategies to expand habitat protection for immature green turtles across their greater distribution

Valvuloarterial Impedence, Strain, Exercise, and AS

Background - In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess the incremental prognostic value of resting valvuloarterial impedence (Zva) and left ventricular global longitudinal strain (LV-GLS) to treadmill stress echocardiography. Methods and Results - We studied 504 such patients (66±12 years, 78% men, 32% with coronary artery disease who underwent treadmill stress echocardiography between 2001 and 2012. Clinical and exercise variables (% of age-sex predicted metabolic equivalents [%AGP-METs]) were recorded. Resting Zva ([systolic arterial pressure+mean aortic valve gradient]/[LV-stroke volume index]) and LV-GLS(measured offline using Velocity Vector Imaging, Siemens) were obtained from the baseline resting echocardiogram. Death was the primary outcome. There were no major adverse cardiac events during treadmill stress echocardiography. Indexed aortic valve area, Zva, and LV-GLS were 0.46±0.1 cm2/m2, 4.5±0.9 mm Hg/mL per m2 and -16±4%, respectively; only 50% achieved >100% AGP-METs. Sixty-four percent underwent aortic valve replacement. Death occurred in 164 (33%) patients over 8.9±3.6 years (2 within 30 days of aortic valve replacement). On multivariable Cox survival analysis, higher Society of Thoracic Surgeons score (hazard ratio or HR 1.06), lower % AGP-METS (HR 1.16), higher Zva (HR 1.25) and lower LV-GLS (HR 1.12) were associated with higher longer-term mortality, while aortic valve replacement (HR 0.45) was associated with improved survival (all P<0.01). Sequential addition of ZVa and LV-GLS to clinical model (Society of Thoracic Surgeons score and %AGP-METs) increased the c-statistic from 0.65 to 0.69 and 0.75, respectively, both P<0.001); findings were similar in the subgroup of patients who underwent aortic valve replacement. Conclusions - In asymptomatic patients with severe aortic stenosis undergoing treadmill stress echocardiography, LV-GLS and ZVa offer incremental prognostic value