Dysregulation of Arginase Isoenzymes in FL-HCC: Investigating the Impact of Nonspecific Arginase-Isoform Antibodies on the Market

In this project, we investigated the expression of the isoenzymes Arginase 1 (ARG1) and Arginase 2 (ARG2) in fibrolamellar hepatocellular carcinoma (FL-HCC) tissue samples. Previous proteomics data had predicted ARG2 to be up-regulated in FL-HCC without clear indication of dysregulation in ARG1. We utilized western blot analysis to determine protein expression by comparing five FL-HCC patient samples to three normal liver tissue samples. During the analysis, we discovered the non-specificity of several commercially bought ARG2 antibodies. This led to the design and execution of various experiments aimed at troubleshooting and identifying a commercially available ARG2 antibody that is specific for the ARG2 isotype. Once the ARG2 isotype-specific antibody was identified, it was used for western blot analysis. Our data concluded that ARG2 expression is up-regulated in FL-HCC. In addition, our data shows that ARG1 expression is sample-specific, pointing to possible stage-specific dysregulation of ARG1 in FL-HCC tumor samples. Overall, our project demonstrates the importance of verifying isoform-specific antibodies while determining the expression of Arginase isoforms in tissue samples. Our findings have important implications for FL-HCC research, as they suggest that targeting ARG2 may be a promising therapeutic strategy. Additionally, our study highlights the need for careful validation of isoform-specific antibodies in cancer research, which can improve the accuracy and reliability of experimental results

Genetic fingerprinting reveals natal origins of male leatherback turtles encountered in the Atlantic Ocean and Mediterranean Sea

This paper is not subject to U.S. copyright. The definitive version was published in Marine Biology 164 (2017): 181, doi:10.1007/s00227-017-3211-0.Understanding population dynamics in broadly distributed marine species with cryptic life history stages is challenging. Information on the population dynamics of sea turtles tends to be biased toward females, due to their accessibility for study on nesting beaches. Males are encountered only at sea; there is little information about their migratory routes, residence areas, foraging zones, and population boundaries. In particular, male leatherbacks (Dermochelys coriacea) are quite elusive; little is known about adult and juvenile male distribution or behavior. The at-sea distribution of male turtles from different breeding populations is not known. Here, 122 captured or stranded male leatherback turtles from the USA, Turkey, France, and Canada (collected 1997–2012) were assigned to one of nine Atlantic basin populations using genetic analysis with microsatellite DNA markers. We found that all turtles originated from western Atlantic nesting beaches (Trinidad 55%, French Guiana 31%, and Costa Rica 14%). Although genetic data for other Atlantic nesting populations were represented in the assignment analysis (St. Croix, Brazil, Florida, and Africa (west and south), none of the male leatherbacks included in this study were shown to originate from these populations. This was an unexpected result based on estimated source population sizes. One stranded turtle from Turkey was assigned to French Guiana, while others that were stranded in France were from Trinidad or French Guiana breeding populations. For 12 male leatherbacks in our dataset, natal origins determined from the genetic assignment tests were compared to published satellite and flipper tag information to provide evidence of natal homing for male leatherbacks, which corroborated our genetic findings. Our focused study on male leatherback natal origins provides information not previously known for this cryptic, but essential component of the breeding population. This method should provide a guideline for future studies, with the ultimate goal of improving management and conservation strategies for threatened and endangered species by taking the male component of the breeding population into account.Sample collection in Nova Scotia, Canada, was supported by funding from Canadian Wildlife Federation, Environment Canada, Fisheries and Oceans Canada, George Cedric Metcalf Foundation, Habitat Stewardship Program for Species at Risk, National Fish and Wildlife Foundation (USA), National Marine Fisheries Service (USA), Natural Sciences and Engineering Research Council of Canada, and World Wildlife Fund Canada. Funding for US samples was provided by National Oceanic and Atmospheric Administration, Massachusetts Division of Marine Fisheries, National Fish and Wildlife Foundation, and Cape Cod Commercial Fisherman’s Alliance. Funding support for this analysis and for Kelly R. Stewart was provided by a Lenfest Ocean Program Grant

Bostonia: The Boston University Alumni Magazine. Volume 32

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Bostonia

Founded in 1900, Bostonia magazine is Boston University's main alumni publication, which covers alumni and student life, as well as university activities, events, and programs

Injury Rates in Age-Only Versus Age-and-Weight Playing Standard Conditions in American Youth Football

BACKGROUND: American youth football leagues are typically structured using either age-only (AO) or age-and-weight (AW) playing standard conditions. These playing standard conditions group players by age in the former condition and by a combination of age and weight in the latter condition. However, no study has systematically compared injury risk between these 2 playing standards. PURPOSE: To compare injury rates between youth tackle football players in the AO and AW playing standard conditions. STUDY DESIGN: Cohort study; Level of evidence, 2. METHODS: Athletic trainers evaluated and recorded injuries at each practice and game during the 2012 and 2013 football seasons. Players (age, 5-14 years) were drawn from 13 recreational leagues across 6 states. The sample included 4092 athlete-seasons (AW, 2065; AO, 2027) from 210 teams (AW, 106; O, 104). Injury rate ratios (RRs) with 95% CIs were used to compare the playing standard conditions. Multivariate Poisson regression was used to estimate RRs adjusted for residual effects of age and clustering by team and league. There were 4 endpoints of interest: (1) any injury, (2) non-time loss (NTL) injuries only, (3) time loss (TL) injuries only, and (4) concussions only. RESULTS: Over 2 seasons, the cohort accumulated 1475 injuries and 142,536 athlete-exposures (AEs). The most common injuries were contusions (34.4%), ligament sprains (16.3%), concussions (9.6%), and muscle strains (7.8%). The overall injury rate for both playing standard conditions combined was 10.3 per 1000 AEs (95% CI, 9.8-10.9). The TL injury, NTL injury, and concussion rates in both playing standard conditions combined were 3.1, 7.2, and 1.0 per 1000 AEs, respectively. In multivariate Poisson regression models controlling for age, team, and league, no differences were found between playing standard conditions in the overall injury rate (RRoverall, 1.1; 95% CI, 0.4-2.6). Rates for the other 3 endpoints were also similar (RRNTL, 1.1 [95% CI, 0.4-3.0]; RRTL, 0.9 [95% CI, 0.4-1.9]; RRconcussion, 0.6 [95% CI, 0.3-1.4]). CONCLUSION: For the injury endpoints examined in this study, the injury rates were similar in the AO and AW playing standards. Future research should examine other policies, rules, and behavioral factors that may affect injury risk within youth football

Language and social/emotional problems identified at a universal developmental assessment at 30 months

Non peer reviewedPublisher PD

Comparative Analysis of Acid Sphingomyelinase Distribution in the CNS of Rats and Mice Following Intracerebroventricular Delivery

Niemann-Pick A (NPA) disease is a lysosomal storage disorder (LSD) caused by a deficiency in acid sphingomyelinase (ASM) activity. Previously, we reported that biochemical and functional abnormalities observed in ASM knockout (ASMKO) mice could be partially alleviated by intracerebroventricular (ICV) infusion of hASM. We now show that this route of delivery also results in widespread enzyme distribution throughout the rat brain and spinal cord. However, enzyme diffusion into CNS parenchyma did not occur in a linear dose-dependent fashion. Moreover, although the levels of hASM detected in the rat CNS were determined to be within the range shown to be therapeutic in ASMKO mice, the absolute amounts represented less than 1% of the total dose administered. Finally, our results also showed that similar levels of enzyme distribution are achieved across rodent species when the dose is normalized to CNS weight as opposed to whole body weight. Collectively, these data suggest that the efficacy observed following ICV delivery of hASM in ASMKO mice could be scaled to CNS of the rat

Late Cretaceous tectonic history of the Sierra‐Salinia‐Mojave arc as recorded in conglomerates of the Upper Cretaceous and Paleocene Gualala Formation, northern California

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/95005/1/jgrb14012.pd

Dementia risk reduction: why haven't the pharmacological risk reduction trials worked? An in-depth exploration of seven established risk factors

Identifying the leading health and lifestyle factors for the risk of incident dementia and Alzheimer's disease has yet to translate to risk reduction. To understand why, we examined the discrepancies between observational and clinical trial evidence for seven modifiable risk factors: type 2 diabetes, dyslipidemia, hypertension, estrogens, inflammation, omega-3 fatty acids, and hyperhomocysteinemia. Sample heterogeneity and paucity of intervention details (dose, timing, formulation) were common themes. Epidemiological evidence is more mature for some interventions (eg, non-steroidal anti-inflammatory drugs [NSAIDs]) than others. Trial data are promising for anti-hypertensives and B vitamin supplementation. Taken together, these risk factors highlight a future need for more targeted sample selection in clinical trials, a better understanding of interventions, and deeper analysis of existing data