bluuebunny/crossref_metadata_2025 huggingface dataset:
Spirulina platensis inhibits lipopolysaccharide‐induced inflammation through the repression of histone deacetylases in RAW 264.7 macrophages
Authors: Pham Tho Xuan , Kim Bohkyung , Lee Jiyoung
Published: June 2021

We observed a potent anti‐inflammatory effect of Spirulina platensis (SP), an edible blue‐green alga, in vitro and ex vivo. To gain a mechanistic insight into the anti‐inflammatory effect of SP organic extract (SPE), we examined the effect of SPE on the expression of histone deacetylases (HDAC) 1 to 11 in lipopolysaccharide (LPS)‐activated RAW 264.7 macrophages. When macrophages were treated with LPS alone (100 ng/ml), SPE alone (100 μg/ml), or SPE+LPS, mRNA and protein levels of most HDAC isoforms were significantly decreased. However, one striking difference was that HDAC1 and HDAC3 protein levels were markedly decreased by SPE but LPS had a minimal effect. The potent repression of HDAC by SPE was evidenced by a marked increase in histone 3 acetylation to a similar extent to that of 25 nM trichostatin A (TSA), a pan HDAC inhibitor. When LPSactivated macrophages were treated with TSA (25 nM), proinflammatory cytokine expression including tumor necrosis factor α and interleukin 1β was significantly decreased but the reduction was less than that of SPE (50 or 100 μg/ml). The repressive effect of SPE on HDAC is likely cell type‐specific because this effect was also observed in 3T3‐L1 preadipocytes but not in HepG2 and Caco‐2 cells. In conclusion, SPE exerts its anti‐inflammatory effect at least in part by a HDAC‐dependent mechanism via the repression of HDAC1 and HDAC3 in macrophages.

Grant Funding Source: NIH R21AT005152
Fat Embolism Syndrome Following Bone Fracture May Be Exacerbated By LPS
Authors: Molteni Agostino , Torres‐Romero Luis , Black Elizabeth , Friedrich Jessie , Tanner J. Chris , Poisner Alan , Herndon Betty
Published: June 2021

Fat embolism (FES) after major bone fracture may lead to acute respiratory distress but little clinical evidence of lung injury remains. However, a study of patients with severe fractures showed reduced pulmonary function many years post‐injury. In rats modeling FES by i.v. triolein, we saw that despite an apparent full recovery, modest fibrotic damage persisted up to 6 weeks. We tested whether at that time an additional insult could exacerbate the lung effects. The model was established with 0.2 mL triolein i.v. to 18 rats and saline to 18 controls. Six weeks later, each group received (i.p.) lipopolysaccharide (LPS) n=9 or saline n=9. At necropsy 48 hr later BALs, lungs and organs were harvested for study. Lung parenchymal, vascular and bronchial damage was scored by 3 pathologists. Saline controls receiving LPS showed pulmonary arterial medial diameters wider than those of animals given triolein before LPS (p<0.04). Adventitia of lung vessels from triolein treated rats showed a significant difference between saline vs. LPS administration (p<0.02). LPS produced a threefold increase in PMN in BAL. At 6 weeks triolein droplets remained in rat lungs localizing to the subpleural septa, smaller and more widespread when LPS was given. Thus, LPS, a “second hit”, administered after triolein FES model produces a more severe lung damage to pulmonary arteries than does LPS following saline.

Funded: Gelmacher Foundation
Thy1‐positive cell transplantation activates the growth of small hepatocyte‐like progenitor cells in rat livers treated with retrorsine and PH
Authors: Mitaka Toshihiro , Ichinohe Norihisa , Kon Junko , Tanimizu Naoki , Nakamura Yukio , Mizuguchi Toru , Hirata Koichi
Published: June 2021

Thy1 and CD44 are used as markers of hepatic stem and progenitor cells, respectively. We previously reported that transplanted Thy1+ and CD44+ cells isolated from galactosamine (GalN)‐treated rat livers could grow to form hepatic foci in rat livers treated with retrorsine following 2/3 partial hepatectomy (RET/PH). Although the number and the size of foci derived from Thy1+ cells were much smaller than those of foci from CD44+ cells and mature hepatocytes (MHs) at 14 days after transplantation, the livers with Thy1+ cells were bigger than those with CD44+ cells and MHs. In the present study we examined the reason why Thy1+ cell‐transplanted livers became large. Livers were immunohistochemically examined. Coculture of the cells isolated from a GalN‐treated liver and small hepatocytes (SHs) from a healthy liver was performed and the growth of SH colonies was measured. The number and size of small hepatocyte‐like progenitor cells, which are known as hepatic progenitors, were larger in the livers with Thy1+ cells than in the livers with CD44+ cells and MHs. The growth of SHs was enhanced when the cells were indirectly cocultured with Thy1+ cells. These results suggest that Thy1+ cells secrete substances that have the potential to activate the growth of progenitor cells in the recipient livers. This research was supported by the Ministry of Education, Culture, Sports, Science and Technology, Japan.
Engaging under‐represented populations in STEM
Authors: Lee Keefe Christine
Published: June 2021

Elementary and secondary students on Manhattan's Lower East Side perform in the bottom 20th percentile of a nation that is currently ranked 17th worldwide for STEM literacy. To address this educational crisis, Two Bridges Neighborhood Council, a community‐based nonprofit, provides single‐point engagement coupled with long‐term after school and summer camp programming, all based on STEM principles. Culturally relevant programs are tailored to different demographic groups within a highly economically, ethnically, and age diverse community. High‐interest activities (e.g. water quality workshops, nature walking tours) use neighborhood history and urban ecology to hook the audience into participating in longer‐term behavioral ecology, engineering, and citizen science projects. Shorter activities use technology and critical thinking skills, long‐term projects emphasize scientific rigor, data analysis, and collaboration. Partnerships with local companies, organizations, and universities augment our programming and show participants how regional projects can have global significance. For audiences such as ours, with less prior exposure to STEM, we use project‐based learning to harness the excitement of discovery for learners. We find that through this strategy, STEM literacy is increasing in participants of the long‐term programs, and the rate of attendance at single events is increasing.
Visiting Scholars BlastOff! to BECUR
Authors: Ferng Shiana J. , Li J F. , Quiroz Jose M. , Shi Aishan , Schlegel Angela M.
Published: June 2021

The University of Arizona UAN Chapter has organized three outreach activities. The Visiting Scholars Program sends undergraduates into high school science classrooms to present research and provide information on opportunities in science. Presenters also serve as mentors by discussing a “well‐rounded” college experience. Furthermore, teachers support the program and are interested in future interactions. Our BlastOff! Summer Camp is a five‐day program that recruits middle school students from underrepresented populations in the sciences. Campers are exposed to “wet lab” techniques, scientific theories, and hands‐on projects; field trips and guest speakers complement lab activities. In the spring, we invite undergraduates and high school students to present their research at our Biology, Engineering, Chemistry Undergraduate Research (BECUR) Conference. For the poster competition, we offer cash prizes and travel awards to the ASBMB meeting. High school students gain experience at this university‐level conference interacting with UA students and faculty. We select two undergraduates to give seminars and invite a Keynote Speaker from the field of biochemistry or molecular biology.
Somatic genome alterations in triple‐negative breast cancer
Authors: Meyerson Matthew
Published: June 2021

Breast cancer is the most common cause of cancer in women in the United States. Within breast cancer, the “triple‐negative” subtype, which is negative for estrogen receptor and progesterone receptor expression and negative for ERBB2 amplification, is the most deadly and has the fewest targeted therapies. Triple‐negative breast cancer occurs more commonly in young women and in women of African‐American descent.

Identification of somatic genome alterations in cancer has led to development of many targeted therapies. To find such alterations in triple‐negative breasst cancer, we and others have performed systematic high‐throughput sequencing of genomes, exomes, and transcriptomes of these cancers. Here, I will discuss results from our studies, including AKT3 translocation in breast cancer, from The Cancer Genome Atlas, and other studies.
Problem solving in biochemistry: assessment, learning strategies, and preconceptions
Authors: Sensibaugh Cheryl A. , Osgood Marcy P.
Published: June 2021

Discipline‐based education research has produced varied perspectives on defining and assessing scientific problem solving. The goals of this dissertation work are to describe and explain longitudinal performance gaps across a two‐year biochemistry curriculum, as well as to synthesize a more advanced pedagogical understanding of scientific problem solving from previously fragmented sources. Student performance will be measured using the Individual Problem Solving Assessment (IPSA), and achievement rates in each domain of problem solving will describe longitudinal performance. The results of a pilot study indicate that after the first year of the curriculum, domain achievement rates for students pursuing a B.S. in Biochemistry range from 9% to 64%. To explain performance gaps, potential contributors will also be investigated, using two additional measures that reflect alternate views of problem solving. The impact of our corresponding problem‐based learning strategies will also be evaluated. Multivariate multiple linear regression analyses will be used to generate quantitative models of the performance phenomena. Additionally, students’ preconceptions about problem solving are being identified. This study will ultimately elucidate connections among emerging theories of defining and assessing scientific problem solving.

Research support is provided under NSF TUES Award #DUE‐1043079.
Understanding dietary behaviors of children with type 1 diabetes using theory of planned behavior
Authors: Lee Soo‐Kyung , Noh Na‐Yeon , Nam So‐Young , Kang Hee‐Sook , Lee Ji‐Eun
Published: June 2021

Type 1 diabetes among children is increasing worldwide. Healthy diabetic diets are important to ensure growth and development, while postponing complications from the disease. This study aimed to understand dietary behaviors of children (7–20 year old) with type 1 diabetes using theory of planned behavior. A pre‐tested questionnaire was used to obtain information from 32 children followed by the department of Pediatrics, Inha University Hospital. The scores for attitude toward behavior, subjective norm, perceived behavioral control, and behavioral intention were 26.2+2.9, 24.1+3.4, 15.8+2.6, and 4.0+0.6, respectively. Multiple regression analyses showed that attitude toward behavior and subjective norm were positively related to behavioral intention, but perceived behavioral control were negatively related to behavioral intention. Only attitude toward behavior was statistically associated with behavioral intention (p<0.05). Behavioral intention was significantly associated with behavior (p<0.05). The findings of this study indicated how powerful the attitude variable is to behavioral intention and behavior, given that the small sample of 32 children provided sufficient statistical power. This study showed that nutrition education with children with type 1 diabetes should emphasize cultivating good attitude toward behavior.
The Longitudinal Association of Vitamin D Serum Concentration and Lipid Profile in Older Puerto Ricans
Authors: Jamal‐Allial Aziza , Tucker Katherine L
Published: June 2021

Vitamin D deficiency is prevalent. Several reports suggest an association between plasma 25‐hydroxy vitamin D concentration (25(OH)D) and cardiovascular disease (CVD). We examined, cross‐sectionally and longitudinally, the relation between serum 25(OH)D concentration and lipid profile at baseline and 2‐year of 1148 Puerto Rican adults, 325 men and 823 women, aged 45–75 years at the Boston Puerto Rican Health Study (BPRHS). Cross sectional analyses at two year time point showed that, among all participants, only high‐density lipoprotein (HDL‐C) was significantly association with higher plasma 25(OH)D (P<0.01); but not low‐density lipoprotein, triglycerides, or total cholesterol. In contrast to expectation, longitudinal analyses showed that baseline 25(OH)D was significantly inversely associated with two‐year HDL‐C (P<0.04), controlling for age, sex and baseline HDL‐C. This remained significant (P<0.05) after adjustment for known contributors to HDL‐C. In conclusion, although 25(OH)D serum concentration was positively associated with HDL‐C in cross‐sectional analyses, longitudinal analyses showed that higher 25(OH)D concentration did not translate into increases in the atheroprotective HDL‐C over time in this population of older Puerto Rican adults living in the Boston area. This study was supported by National Institutes of Health grants P01 AG023394 and P50 HL105185
Child growth from age 1 to age 8 y in four low‐and middle‐income countries: Young Lives
Authors: Lundeen Elizabeth A , Behrman Jere , Crookston Benjamin , Dearden Kirk , Engle Patrice , Georgiadis Andreas , Penny Mary , Stein Aryeh
Published: June 2021

Objective

We characterized child growth patterns in four countries and assessed the degree of recovery from linear growth retardation.

Design

We analyzed length/height at ages 1, 5, and 8 y for a cohort of 7,259 children in Ethiopia, India, Peru and Vietnam.

Results

Mean height‐for‐age z score (HAZ) at age 1 y ranged from −1.83 (Ethiopia) to −1.14 (Vietnam). From ages 1 to 5 y, mean HAZ increased by 0.34 in Ethiopia and decreased among the other countries (range: −0.20 to −0.30). From 5 to 8 y, mean HAZ increased in all the countries (range: 0.20 to 0.38). Stunting prevalence at 1 y ranged from 21.4% (Vietnam) to 46.5% (Ethiopia). From 1 to 5 y, stunting prevalence decreased 15.1 percentage points (PP) in Ethiopia and increased in the other countries (range: 3.1 to 5.3 PP). From 5 to 8 y, stunting prevalence decreased in all the countries. Among children stunted at 1 y, 45% (Vietnam and India) to 66% (Ethiopia) were non‐stunted by 8 y. 40–71% and 26–45% of variance in HAZ at 5 and 8 y, respectively, was not predicted by HAZ at earlier ages.

Conclusions

HAZ at age 1 y is predictive of HAZ at ages 5 and 8, but after age 1 there is substantial increase in HAZ overall and substantial unpredicted variation in HAZ change that might be amenable to household interventions and caretaker behaviors after age 1.

Source of research support: Bill & Melinda Gates Foundation and Eunice Shriver Kennedy National Institute of Child Health and Development.
Effect of grape seed extract delivered in a beverage on blood pressure in individuals with pre‐hypertension
Authors: Park Eunyoung , Wuchner Brittany , Huang Yancui , Joseph Shama , Edirisinghe Indika , Burton‐Freeman Britt
Published: June 2021

Hypertension (HTN) is a major risk factor for heart disease and stroke. Extracts derived from grape seeds are known to reduce blood pressure (BP). The aim of this study was to investigate the effect of grape seed extract (GSE) in a beverage on BP in individuals with pre‐HTN.

Ambulatory (12 hr, day) BP before and after 6 week consumption of GSE beverage (300 mg/day) or placebo beverage was measured in randomized parallel design (n=36, 1:1). Means of age, BMI and initial systolic (S)/diastolic (D) BP were 42±10 y, 32±8 kg/m2, and 128±8/83±7 mmHg, respectively.

Significant reductions in SBP (GSE −7.4±2.3 vs placebo 1.6±1.9 mmHg, p=0.003) and DBP (GSE −3.8±1.6 vs placebo 0.7±1.3 mmHg, p=0.03) were observed after 6 weeks GSE beverage compared to the placebo beverage. The effectiveness of GSE was improved in subjects with SBP above the median (≥ 125 mmHg) (GSE −14 ± 2.5 vs placebo −0.6±2.2 mmHg, p<0.05) and in subjects with DBP above the median (≥ 83 mmHg) (GSE −5.7±1.9 vs placebo 0.7±1.4 mmHg, p<0.05). Changes in insulin (p=0.07) and significant changes in HOMA value (p<0.05) were found after 6 weeks GSE beverage compared to the placebo beverage.

The present study supported the use of GSE as a functional ingredient in a low calorie beverage to reduce the risk of HTN and may aid in glucose control through improved insulin sensitivity; the latter requires further investigation.

Grant Funding Source: Polyphenolics Inc., Madera, CA
Acute Administration of n‐3 Triglyceride Emulsion Provides Marked Cardioprotection After Ischemia/Reperfusion
Authors: Zirpoli Hylde , Abdillahi Mariane , Quadri Nosirudeen , Ananthakrishnan Radha , Zhu Zhengbin , Wang LingJie , Li Qing , Deckelbaum Richard J , Ramasamy Ravichandran
Published: June 2021

n‐3 fatty acids may decrease cardiovascular disease risk. We questioned if acute intervention of n‐3 triglyceride (TG) emulsion (48% of fatty acids = EPA+DHA) is protective and improves cardiac function after ischemia/reperfusion (I/R). n‐3 TG were administered after I/R in two models: a) hearts (C57BL/6 mice) were perfused ex‐vivo using the Langendorff technique (LT); b) hearts with acute occlusion of the left anterior descending coronary artery (LAD) in vivo. After LAD occlusion n‐3 TG emulsion (1.5g/kg body weight) was injected intraperitoneally at the end of ischemia and 1h later. In the LT model of I/R, perfusion with KREBS‐Hensleit buffer (KH) led to markedly decreased left ventricular developed pressure (LVDP) (by 60%) and arrhythmias, but reperfusion with KH+ n‐3 TG (300mg/100ml) improved LVDP recovery. In the LAD model, near normal echo‐and electrocardiograms were maintained 48hrs after I/R and left ventricular infarct size was reduced by 80% in TG treated animals vs control. For both I/R models, markers of injury, lactate dehydrogenase and creatine kinase, were significantly reduced in n‐3 TG treated mice. After I/R, in LT model, n‐3 TG increased a marker of apoptosis Bcl‐2 (by 50%), reduced markers of autophagy beclin 1 (by 60%) and HIF1 (by 80%). We conclude that an acute n‐3 TG injection after ischemia provides cardioprotection. This may provide a novel therapy after acute myocardial infarction in humans.

Grant Funding Source: Nutrition (ASN)
Evaluating Mass in Motion Kids (MiM Kids): A Multi‐Sector Intervention to Reduce Childhood Obesity Using a Community‐Clinical Partnership
Authors: Falbe Jennifer , Davison Kirsten K. , Taveras Elsie M. , Gortmaker Steven L. , Anand Shikha G. , Blaine Rachel E. , Criss Shaniece R. , Perkins Meghan , Kwass Jo‐Ann , Land Thomas , Smith Lauren A.
Published: June 2021

MiM Kids is one of three 4‐year projects funded through the CDC's Childhood Obesity Research Demonstration Project to reduce obesity and improve health behaviors in children ages 2–12 years. Implemented in two low‐income communities in Massachusetts, MiM Kids uses evidence based interventions in clinics, schools, after‐school programs, child care, and the community at large. Using a combination of pre‐post time series and quasi‐experimental designs and comparing two intervention communities to one control community, the effectiveness of MiM Kids is examined in reference to individual lifestyle behaviors, change in body mass index (BMI), satisfaction with health care, and quality of life. Data collection integrates robust and efficient clinical and community data acquisition processes including school BMI data, electronic medical record extraction, parent surveys, environmental audits, document reviews, and community stakeholder interviews. In addition to the local evaluation, common measures developed in coordination with an evaluation center will be utilized across CORD sites. Community interventions hold great promise, but there is limited evidence for the effectiveness of multi‐sector interventions. MiM Kids and its evaluation advances community nutrition intervention science by filling this gap. Findings may inform local and state policy and future community interventions.

Grant Funding Source: Centers for Disease Control and Prevention: U18DP003370–01. This work is solely the responsibility of the authors and does not represent the official views of the CDC.
Exploring the Relationship between Perceived Stress and Weight Loss
Authors: Shen Mary Rebecca , Nezami Brooke T. , Crane Melissa , Tate Deborah F
Published: June 2021

Research shows perceived stress (PS) is related to weight gain, but few studies have examined PS during a weight loss attempt. We hypothesized that higher PS would be associated with lower treatment adherence and less weight loss and we explored how change in PS during treatment is associated with weight loss.

This data is from a 4‐month weight loss RCT intervention delivered via Internet and monthly in‐person sessions (N=192, 46.3±10.8 yrs, BMI 37.9±8.5, 91% women, 51% African‐American). Percent weight loss (WL) was calculated from measured weight and PS by the Perceived Stress Scale (range 0–40) at baseline and 4 months. Adherence was defined as website logins and group attendance. Intent‐to‐treat analyses (BOCF) controlled for group, race and education.

Overall, PS decreased over time (17.1±5.8 to 14.3 ±6.7). Among women (n=175), baseline PS did not predict WL (p=.56) but decreases in PS were associated with greater WL (p<.01). In an exploratory analysis of men (n=17), baseline PS predicted WL (p<.01) but there was no association between PS change and WL (p=.80). Adherence was associated with WL (p's<.01), but baseline PS was not associated with adherence (p's >;.20).

Baseline PS was associated with WL in men while reductions in PS were associated with WL in women. It is unclear how PS changes affect WL as PS was not associated with adherence. These results suggest the relationship between PS and WL may vary by gender.

Grant Funding Source: Office of Undergraduate Research at UNC‐Chapel Hill
High dietary protein intake results in lower intra hepatic lipid content in healthy humans on a hypercaloric high‐fat diet
Authors: Rietman Annemarie , Schwarz Jessica , Siebelink Els , Kok Frans , Tomé Daniel , Mensink Marco
Published: June 2021

High‐protein diets may improve regulation of body weight and glucose homeostasis and, at least in animals, reduce intra hepatic lipid content. Our objective was to reduce intra hepatic lipids (IHL) in healthy humans, by increasing protein (P) intake at the expense of carbohydrates (CH), in a high‐fat‐hypercaloric‐diet.

A strictly controlled dietary intervention was performed in lean healthy subjects, who were randomly assigned to the intervention groups. One group received a balanced‐diet (BD‐group; n=10) (28 en% fat; 17 en% P; 55 en% CH) for 4 weeks. The other group (n=17) received a hypercaloric high‐fat diet (HD‐group; + 2 MJ per day, 40 en% fat) in a 2‐week cross‐over design, with a high protein content (HP; 26 en% P) or a normal protein content (NP; 15 en% P) and vice versa.

On the HD diet there was a trend for lower IHL on HP compared to NP (difference 0.2 %, p=0.08); and a trend for increased IHL after BD compared to HD was seen (difference 0.13 %, p=0.06). Body weight did not differ between HP and NP, however fat mass was lower (−0.27 kg, p=0.02) and lean mass was higher (+0.52 kg, p=0.003) on HP compared to NP. Fasting insulin sensitivity and plasma triglyceride levels did not differ between protein diets.

To conclude, high dietary protein intake, at the expense of carbohydrates, resulted in lower IHL in healthy humans, receiving a hypercaloric high‐fat diet. This research was supported by the Dutch Dairy Organisation (NZO).
Fruit and vegetable intake and bladder cancer risk: the Multiethnic Cohort Study
Authors: Park Song‐Yi , Ollberding Nicholas J. , Woolcott Christy G. , Wilkens Lynne R. , Henderson Brian E. , Kolonel Laurence N.
Published: June 2021

Fruits and vegetables have been examined for their possible effects on the risk of bladder cancer, as they contain numerous nutrients and phytochemicals with anticarcinogenic properties. We examined whether the consumption of fruits and vegetables, or of nutrients concentrated in fruits and vegetables, was associated with bladder cancer risk among 185,885 older adults in the Multiethnic Cohort Study. A total of 581 invasive bladder cancer cases were diagnosed over a mean follow‐up period of 12.5 years. In women, total fruits and vegetables (HR for the highest vs. lowest quartile = 0.35; 95% CI: 0.22, 0.56), total vegetables, the specific vegetable subgroups of yellow‐orange vegetables and cruciferous vegetables, total fruits, and citrus fruits were inversely associated with the risk of bladder cancer. In addition, women with the highest intakes of vitamins A, C, and E; the carotenoids ¥á‐carotene, ¥â‐carotene, ¥â‐cryptoxanthin, and lutein; folate; and dietary fiber had a lower risk of bladder cancer. For men, no associations were detected overall, although inverse associations were seen for vegetable intake among current smokers, and in ethnic‐specific analyses, for fruit and vegetable intake among Latinos specifically. Our findings suggest that greater consumption of fruits and vegetables may lower the risk of bladder cancer among women and highlight the need for specific subgroup analyses in future studies.
The role of wnt/β‐catenin signaling in regulating angiogenesis in hepatocellular carcinoma
Authors: Delgado Evan R , Bahal Raman , Ly Danith , Monga Satdarshan P. S.
Published: June 2021

Hepatocellular carcinoma (HCC) is the third cause of death by cancer worldwide. Activating β‐catenin gene mutations are observed in 30% of HCC and with its role in tumor cell survival and proliferation, β‐catenin is an attractive therapeutic target. However, its role in regulating angiogenesis in HCC remains obscure. Here, we characterize the role of β‐catenin in regulating angiogenesis and address its effect on endothelial cells. S33Y‐mutant but not wild‐type (WT) β‐catenin transfection in Huh7 and Hep3B cells resulted in increased expression of pro‐angiogenic secreted factors such as VEGF‐A. Concomitantly, we used a novel, cell permeable gamma guanidine‐based peptide nucleic acid (γGPNA) antisense oligonucleotide designed against the transcription start site (T1) of the human β‐catenin gene. Using TOPflash luciferase reporter assay, we show that γGPNA decreases Wnt/β‐catenin activity in HCC cells harboring activating β‐catenin mutations (HepG2 & Snu‐449). qRT‐PCR confirmed suppression of β‐catenin and western blot showed decreased protein expression of β‐catenin targets including glutamine synthetase (GS), cyclin‐D1, and VEGF‐A. Angiogenesis qRT‐PCR array also identified downregulation of several pro‐angiogenic secreted factors such as EphrinA1, FGF‐2, and VEGF‐A upon β‐ catenin inhibition. Conditioned media from γGPNA treated HepG2s was sufficient to reduce spheroid and tube formation by HCC‐associated endothelial cells (SK‐Hep1). Thus, our study shows an important role of β‐catenin in angiogenesis and validates it to be a major therapeutic target due to its roles in tumor cell viability, proliferation, metabolism and now in angiogenesis.
1,25(OH)2D3 decreases leptin, IL‐6 and SAA expression in human adipocytes: role of vitamin D receptor
Authors: Lee MiJeong , Nimitphong Hataikarn , Guo Weimin , Holick Michael F , Fried Susan K
Published: June 2021

Low vitamin D status is associated with human obesity, and higher risk for insulin resistance and development of Type 2 Diabetes. Vitamin D has anti‐inflammatory effects in macrophages and recent studies proposed a role of vitamin D in adipose tissue inflammation and adipokine expression. To test the effects of 1,25(OH)2D3 on adipokine secretion, human adipose tissue explants were cultured with or without 1,25(OH)2D3 (10–8 M). 1,25(OH)2D3 decreased mRNA levels and secretion of leptin, IL‐6, and SAA by 40–50% without affecting MCP‐1 and adiponectin expression. To test direct effects of 1,25(OH)2D3 on adipocytes, we also tested its effects in human adipocytes in culture. Similar to adipose tissue explants, 1,25(OH)2D3 (10–8 M) decreased leptin and IL‐6 by 50–60% in primary human adipocytes in culture, demonstrating the effects of 1,25(OH)2D3 at the level of adipocytes. Using RNAi, we further assessed whether the effects of 1,25(OH)2D3 on adipokines were mediated through the vitamin D receptor (VDR). When VDR protein levels were reduced (>;80% knockdown), 1,25(OH)2D3 did not affect leptin and IL‐6 secretion, demonstrating the effects of 1,25(OH)2D3 are mediated through the VDR. Overall, these results demonstrate that vitamin D has anti‐inflammatory actions in human adipose tissue and adipocytes, and suggest this mechanism may link higher vitamin D status with reduced risk of T2D found in epidemiological studies.
First year cohort results for the NCI R25 University of Louisville Cancer Education Program
Authors: Hein David W , Kidd La Creis R
Published: June 2021

The University of Louisville recently initiated a program to recruit, educate and motivate outstanding undergraduate and health professional students to pursue further training and careers in cancer research. We received over 50 applications and funded 28 participants in the first year. The final section included 11 medical, 2 dental, 1 graduate and 14 undergraduate students. Over 60% were female and over 30% were African‐American. Each of the students completed the curriculum and a cancer research project. All of the students presented research posters and prizes were awarded to the top students and their mentors in both the professional and undergraduate student categories. A blinded and electronic survey of the student participants was performed to assess participant interest in cancer research before and after completing this year's program. The survey was evaluated on a likert scale of 1) poor; 2) could be better; 3) neutral; 4) good; and 5) excellent. Aggregate evaluation scores (Mean ± SEM; n=23) increased significantly (p=0.0092) following completion of the program (4.30 ± 0.17) compared to the scores from the same participants at entrance (3.57 ± 0.21). The evaluation score for the overall program experience was 4.26 ± 0.24. The program was an excellent vehicle for recruitment into the pharmacology and toxicology graduate program. (Partially supported by NCI grant R25CA134283).
Creating clinically relevant, integrated cases in the biomedical and pharmaceutical sciences
Authors: Soltis Robert , Pandit Nita
Published: June 2021

There is a body of convincing evidence that providing problem‐solving exercises in the form of patient cases can enhance student learning in the biomedical sciences. The challenge for basic scientists, however, is creating cases that are not only clinically relevant and scientifically based but also integrate concepts from various disciplines to further enhance problem‐solving skills. We have devised a set of guiding principles to aid in creating clinically relevant, integrated cases in the biomedical and pharmaceutical sciences. 1) Scientific focus: The case should provide a thorough analysis of a scientific concept with an emphasis on the “why” rather than facts or the “what”. 2) Integration: To provide context and deeper understanding of a scientific concept, the case should draw upon knowledge from other disciplines to provide the basis for application. 3) Clinical relevance: A simple, plausible clinical scenario, rather than a complex patient case, provides a link between the science and the patient and makes the application recognizable to the student. 4) Take home message: The over arching educational intent of the case should be 1–2 key scientific concepts that enable the student to see the big picture and provide the underlying scientific basis of clinical decisions. Samples of cases and evidence supporting student progress on developing problem solving skills will be presented.
Age and gender specific characteristics of spongy bone architectonic in lumbar vertebral bodies
Authors: Mavrych Volodymyr , Bolgova Olena , Sankova Larisa
Published: June 2021

Background

A spine is one of the most often places of fractures in patients with an osteoporosis. Approximately 25% of all women in the world at the age of 70 and 50% of women at the age of 80 years have individual or plural compression fractures of vertebral bodies. The purpose of the research was to establish the age and gender related features of trabecular architectonic in human lumbar vertebra bodies.

Methods

212 lumbar vertebrae (0 – 88 years old) were utilized. On the digital images of the sagittal sections 3rd lumbar vertebrae were investigated length and diameters vertical and horizontal trabeculae, width of intertrabecular spaces using computer complex “Morpholog” (Fig.1).

Results

Our data suggests that all investigated parameters have a significant age correlation (p<0.0001). During the life time the length of horizontal and vertical trabeculae increases continuously for male and female, as well as, the width of the intratrabecular spaces. Diameters of vertical (Fig.2) and horizontal trabecules (Fig.3) increase from 175.3±6.8 and 73.2±8.2 microns in newborns and reach its peak in late adulthood from 247.8±28.6 and 124.2±10.9 microns; later it diminishes to 243.3±36.0 and 101.4±11.7 microns in elderly stage.

Conclusions

Until elderly age growth of trabeculae was evident. During involution in elderly age, the height of vertebral bodies and trabecular diameters decreases due to osteoporosis.
To Be Or Not To Be A Wolf During The Pleistocene, That Is The Question
Authors: Koper Lindsey
Published: June 2021

At the end of the Pleistocene (10,000 years ago), there was a worldwide megafaunal extinction that included both large carnivores and herbivores. Before the extinction event, two kinds of wolf‐like canids lived along side each other for a couple hundred years in North America. This coexistence is well‐documented, based on the multitudes of fossil specimens of Canis dirus and Canis lupus from the Rancho La Brea tar pits in Los Angeles. The larger of the two, C. dirus, died out during the megafauna extinction whereas C. lupus still lives and thrives today as a top predator. It is not known why certain species went extinct during this time while others survived but the diet of C. dirus and C. lupus may have been responsible. According to the literature, C. dirus is more of a hypercarnivore compared to other canids or shows more characteristics of having a diet that is more exclusively meat based. C. lupus is a more generalized carnivore based on its dentition and varied diet. The difference between these carnivores can be seen in the size and shape of the carnassial teeth and the more posterior dentition. My study, analyzes the surface area of the dentition of both C. dirus and C. lupus to determine if they indeed had slightly different diets. If so, then I hypothesize that C. lupus was and is a more adaptable carnivore, allowing it to expand its diet during the megafaunal extinction, giving it advantage over the now extinct C dirus.

Grant Funding Source: Northern Illinois University
Morphological, mechanical and biochemical changes in long bones following spinal cord injury
Authors: Zamarioli Ariane , Morse Leslie , Battaglino Ricardo , Maranho Daniel , Volpon Jose B , Paula Francisco A , Shimano Antonio C
Published: June 2021

Spinal cord injury (SCI) is associated with rapid and intense bone loss and higher fracture risk. We aimed to assess the effects of a complete SCI and passive standing post‐SCI on the bone metabolism in rats. Severely injured with and without passive standing and body weight‐matched uninjured male Wistar rats were studied. Serum bone turnover and long bones (mechanical tests, macroscopic analysis, histological sections and micro‐CT) were analyzed on days 33 and 63 post‐SCI. At study entry, rats’ body mass was similar among the groups. Uninjured rats gained weight during the course of the study. SCI rats also gained weight, but not in the same proportion. Morphological changes were seen at the macroscopic structures of both femur and tibias, such as decreased bones mass and cross‐sectional area. Reduction of the bone saliences in tibias, as anterior tuberosity and posterior muscle insertions were also seen in the SCI rats. Our microscopic analysis (histology, scanning electronic microscopy and micro‐CT) showed increased number of osteoclasts and trabeculae spacing, reduced trabeculae number, thickness and connectivity. SCI also reduced OPG levels, increased TRAP and caused a significant reduction in bone strength at both femur and tibia on days 33 and 63. The changes caused by the SCI on the bone metabolism were ameliorated and even reverted following passive standing.
Doxorubicin‐induced Cardiomyopathy in the giant danio is associated with Apoptosis, Inflammation, and Collagen Accumulation
Authors: Johnson Adedoyin , Manalo Trina , Tomamichel Wendy , Lafontant Pascal J
Published: June 2021

Doxorubicin (Dox), an antineoplastic anthracycline used in the treatment of childhood leukemia, is associated with late‐onset cardiomyopathy. The mechanisms of Dox‐induced cardiac dysfunction are an area of intense investigations. Using light and transmission electron microscopy (TEM), we studied the effects of Dox on the heart of giant danio (GD), a small fish closely related to zebrafish. We compared short‐term high‐dose to long‐term low‐dose effects of Dox administrations. We found that short‐term (4 days) high‐dose Dox induced little inflammation or collagen accumulation in the GD myocardium. By contrast long‐term (4 weeks) low‐dose Dox induced apoptosis (TUNEL, TEM) and inflammation (MPO, TEM) in the ventricular myocardium. The number of MPO‐positive cells increased by 2 folds and 4 folds in Dox‐treated hearts, at 1 and 4 weeks respectively, with cell cycle activity (Edu) in cardiac myocytes (CM) and increased fibrosis (Trichrome, TEM). Interestingly, we found a spatially‐restricted pattern of fibrosis in the compact heart (CH). Consistent with this finding we observed by TEM that activated fibroblasts in the CH contributed to collagen accumulation. This data suggests that, except for marked cell cycle activation in CM, the GD heart response to Dox treatment appears analogous to that of human. Thus the GD may serve as an important model for the study of Dox‐induced cardiomyopathy.

Grant Funding Source: FDC
Gene expression analyses of a regenerative cardiac model system in Ciona intestinalis
Authors: Manning Caitlin LaShea , Pardhanani Pooja , Barth Jeremy , Evans‐Anderson Heather
Published: June 2021

Ciona intestinalis is a useful invertebrate animal model system for studying the role of evolutionarily conserved genes among Chordates. In contrast to most vertebrates, Ciona hearts have the capacity for regeneration throughout their lifespan. An injury model system was used to stimulate regeneration in Ciona hearts. In order to identify genes that are involved in regeneration of the Ciona heart, microarray analysis was conducted on RNA from adult hearts with normal or damaged myocardium using custom Affymetrix GeneChips. Initial results indicate significant changes in the expression of 223 genes in hearts damaged by ligation in comparison to control hearts (fold change >;2, p<0.01, Student's t‐test) with limited false discovery (5.8%). Among these 223 genes, 117 have known orthologs to vertebrates, of which 68 genes were up‐regulated and 49 genes were down‐regulated. Altered orthologous genes were validated by RT‐PCR. In addition, expression patterns of genes identified in the microarray study are currently being identified via in situ hybridization in juvenile and adult Ciona hearts. Genes of interest include: ciFGF 9/16/20, ciFoxO, and ciFoxP. In combination, these studies will help to elucidate the genetic basis of myocardial regeneration in Ciona and provide further insight into the role of orthologous genes in the regulation of cardiac myocyte proliferation.

Grant Funding Source: NIH R15 Area Grant
Broad genotyping of consecutive endometrial cancer samples enables the identification of rare and novel mutations
Authors: Stachler Matthew D. , Lindeman Neal
Published: June 2021

Previous genetic analyses of endometrial cancer have either suffered from analyzing a small set of genes or a limited number/selected subset of samples. Both hinder the ability to find rare mutations that may be clinically relevant. Here we describe the results of broadly genotyping consecutive samples of endometrial cancer. Endometrial cancer samples containing >;250 ng of DNA were genotyped for 471 mutations in 41 cancer‐associated genes using a PCR‐mass spectrometry assay (Sequenom). Of the 152 endometrial tumors, 113 showed endometrioid (EACA) histology, 15 serous, 6 poorly differentiated/mixed, 5 clear cell, and 13 adeno/carcinosarcomas. 88(78%) of the EACAs contained at least one mutation. The type or number of mutations in a given sample did not correlate with either grade or presence of metastasis. Several mutations were identified in EACA that had not been reported as frequent findings in this tumor type (AKT1, MET, APC), including a mutation in MYC (p. A59V) that is, to our knowledge, novel in this tumor type. Routine tumor genotyping enabled the identification of mutations not commonly associated with the given tumor type. Clinically, this could provide valuable unanticipated information for targeted therapy [PIK3CA, IDH1]. In addition, genotyping enables correlation between combinations of mutations and, potentially, clincopathologic features, potentially suggesting new areas of research.
Comparing CT to surface digitization‐based measurements of cartilage thickness
Authors: Yeung Celine , Willing Ryan , Shannon Hannah , Lalone Emily , Johnson Marjorie , King Graham , Athwal George S.
Published: June 2021

Background

Knowledge of cartilage thickness distribution is important for understanding the biomechanical properties of different joints. In recent studies, various techniques for measuring cartilage thickness have been assessed.

Objective

Compare the reliability of computed tomography (CT) and surface digitization‐based methods for measuring cartilage thickness.

Methods

Six cadaveric radii were CT scanned in air, barium sulfate, and iopamidol to determine which medium enabled optimal cartilage visualization. Images of cartilage in the best medium were used to generate three dimensional (3D) models for measurement. The radial heads were then digitized using an infrared motion tracking system. Cartilage thickness was measured as the distance from the deepest point on the cartilage surface to the bone. Both CT‐ and surface digitization‐based values were compared to physical measurements acquired using a digital caliper to determine which technique was most reliable for assessing cartilage thickness.

Results

CT and surface digitization had mean differences of −0.01±0.06mm (mean ± standard deviation) and 0.00±0.35mm, respectively. Surface digitization‐based measurements, however, had larger individual errors and a greater range of error (−0.42 to +0.62mm) compared to CT‐based measurements (−0.07 to +0.08mm).

Conclusions

CT is a more reliable technique for assessing cartilage thickness.

Grant Funding Source: Departmental
Stage and sub‐field associated microRNA changes in epilepsy
Authors: Kanagaraj Nandhini , Li Yue , Dheen S T , Tay Samuel SW
Published: June 2021

Epilepsy is a neurological disease characterized by chronic, recurring seizures and affects about 50 million people worldwide. Of the two major cell groups in the hippocampus, CA1 pyramidal neurons are prone to excitotoxicity and degeneration while the granule cells of the dentate gyrus (DG) exhibit seizure resistance and neurogenesis during epilepsy. MicroRNAs(miRNAs) are small, non‐coding RNAs recognized as significant regulators of gene expression. While there are reports of miRNA changes in epilepsy, none of them have analyzed the differential miRNA expression in the DG and CA1 regions. In order to identify the changes in miRNA expression in both regions we performed a miRNA microarray of the DG and CA1 regions from pilocarpine‐induced epileptic mice at 3, 14 days and 2 months after induction of epilepsy.164 miRNAs in DG and 111 miRNAs in CA1 were differentially expressed as compared to control at all three time points (p<0.01). Of these, 79 miRNAs were common between DG and CA1, 85 were only in DG and 32 only in CA1. The expression of 5 randomly picked deregulated miRNAs was confirmed using qPCR. Using web‐based databases and a PCR array for mRNA expression we have identified 6 signal transduction pathways modulated by the deregulated miRNAs. These results provide an insight into the miRNA‐based differential regulation of signal transduction pathways in CA1 and DG regions during status epilepticus. Supported By BMRC grant ‐R.181.000–129‐305.
Sequence Analysis of PTEN in Castanea dentata and PINK1 in Caenhorabditis elegans
Authors: DeGennaro Torrie Lynn , Dwyer Megan Marie , Gallagher Madison Elizabeth , Korolyshun Rachel , Riccardi Olivia Elizabeth , Paolella Mary Jane
Published: June 2021

This study analyzes the sequences of PTEN (phosphatase and tensin homologue) and PINK1 (PTEN induced putative kinase 1) in Castanea dentata, American Chestnut, and Caenorhabditis elegans respectively. Their genetic mutations can be the cause of breast cancer and Parkinson's Disease. PTEN provides instructions for making a protein found in all tissues of the body and PINK1 furnishes the instructions for making PTEN. The American Chestnut (provided by the CT Agricultural Station) has been subjected to blight in the eastern forests. The worms (obtained from Cold Spring Harbor/DNA Learning Center) share fundamental cellular and molecular structures with humans. A variety of DNA extraction methods were employed including FTA cards, Extract‐n‐Amp, DNeasy kits and specific lab protocols developed for the chestnut by Jeanne Romero‐Severson (U. Notre Dame) and for the worms by James Lissemore (John Carroll University). PCR was performed using student‐designed primers and protocols after careful alignment of genetically similar organisms. The results were then used as templates to sequence the genes on the school‐owned ABI Prism 310 Genetic Analyzer and analyzed using NCBI and Ensembl bioinformatics tools. The results will be submitted to GenBank in June..
Loss of redoxin proteins exacerbates LRRK2‐mediated Parkinson's disease phenotype in C. elegans
Authors: Johnson William Marshall , Yao Chen , Chen Shu , Wilson‐Delfosse Amy L. , Mieyal John J.
Published: June 2021

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide, and oxidative stress is considered a major contributor to PD pathogenesis. Recently, we and others found that pathogenic mutations in the leucine rich repeat kinase 2 (LRRK2) gene linked to familial PD promote increased ROS generation in model neuronal cells in culture.

The redoxin family of proteins, including peroxiredoxin and glutaredoxin, provides defenses against oxidative stress through peroxide‐scavenging and protein repair mechanisms. Hence, we hypothesized that loss of Prdx‐3 or Grx1 would result in exacerbation of the mutant LRRK2‐dependent PD phenotype.

Previously we demonstrated that expression of mutant human LRRK2 in dopaminergic neurons of C. elegans resulted in impaired dopamine‐dependent behavior and age‐dependent loss of dopaminergic neurons. Here we report that mutant LRRK2 expression concomitant with embryonic knockout of Prdx‐3 or Grx1 exacerbates the impairment of dopamine‐dependent movement and increases the loss of dopaminergic neurons. Notably, knockout of Prdx‐3 alone results in a PD phenotype. Thus, Grx1 and Prdx‐3 may act as novel PD suppressors in vivo. Current studies are focused on molecular mechanisms by which Grx1 and Prdx‐3 may mediate neuronal protection in vivo. Supported in part by NIH grants 5R21NS073170 (SGC & ALW) and T32GM008803 (WMJ), and VA grant BX000290 (JJM).