bluuebunny/crossref_metadata_2025 huggingface dataset:
Anthocyanin compositions and contents influence the antioxidant capacities of berries
Authors: Lee Sang Gil , Nam Tae-Gyu , Kim Dae-Ok , Lee Jiyoung , Koo Sung I. , Chun Ock K.
Published: June 2021

Berries have been shown to have beneficial effects on human health and disease. These effects are mainly attributed to the antioxidant properties of anthocyanins in them. Anthocyanins vary in antioxidant capacity (AC) due to variations in their structures and glycosidic moieties. The present study examined whether the AC of Anthocyanin fractions from berries is influenced by the composition and/or amount of anthocyanins present in them. Anthocyanin fractions were obtained from the phenolic extracts of three berries (blueberry, blackberry, and blackcurrant). Total anthocyanin contents were quantitated using pH differential method and their compositions were confirmed using HPLC. AC was measured using ABTS assay. Glycoside forms of malvidin (36 %) in blueberry, delphinidin (53 %) in blackcurrant, and cyanidin (100 %) in blackberry were predominant. Whereas blueberry contained the highest amount of anthocyanins (844 mg/cyanidin 3‐glucoside (C3G) equiv./100g dry weight) followed by blackcurrant (738 mg), and blackberry (671 mg), the blackberry fraction showed the highest AC (2,110 mg VCEAC/100g), which was associated with the high content of C3G. The findings indicate that the AC of the berries is influenced by the composition, amount, and specific forms of anthocyanins present.
Inflammatory and metabolic changes of severe obese women after 6 months of a Roux‐en‐Y gastric bypass
Authors: Pierine Damiana Tortolero , Biagioni Maria F. , Calvi Sueli A. , Mendes Adriana L. , Paiva Sérgio A. R. , Leite Celso V. , Mazeto Gláucia M. F. S. , Corrêa Camila R.
Published: June 2021

Obesity is a chronic disease related to adipokines production, which contribute to inflammation and metabolic abnormalities. The Roux‐en‐Y gastric bypass is an alternative therapy for the treatment of severe obesity, reaching weight loss superior to conventional therapies. The aim was observed the inflammatory and metabolic changes after 6 months of Roux‐en‐Y gastric bypass. Nine women aged 24 – 48 years old, BMI > 35 kg/m2 (50.9±9.6), submitted to Roux‐en‐Y gastric bypass. Plasma concentrations evaluated: glucose (mg/dL), leptin (pg/mL), adiponectin (ng/mL), TNF‐α (pg/mL) and IL‐6 (pg/mL). Anthropometric assessment: weight (kg), BMI (kg/m2) and fat mass (FM: kg). We observed reduction in body weight (130.1±23.8 × 98.5±25.2, p<0.01) and FM (72.1±17.4 × 40.8±8.3, p<0.01). Significant metabolic changes were found, such as reduction in leptin [431.3 (303.8 – 532.2) × 96.7 (62.0 – 176.8), p<0.01] and glucose [97.0 (84.5 – 107.5) × 82.0 (74.7 – 85.0), p=0.04] and increased adiponectin (62.7±21. 2 × 206.0±120.8, p<0.01). With respect to pro‐inflammatory parameters, no significant changes were observed in TNF‐α (0.44±0.69 × 0.3±0.5, p=0.20) and IL‐6 [4.7 (3.2 – 7.6) × 1.8 (0.9 – 3.8), p=0.12]. Six months after surgery decreased fat mass and resulting in changes as decreased leptin and glucose and increased adiponectin. In other hand in this period there was no change in inflammatory parameters.
C‐Abl Inhibition Exacerbates Mechanical Ventilation‐Induced Lung Injury In A Murine Model
Authors: Sammani Saad , Letsiou Eleftheria , Moreno- Liliana , Camp Sara M , Chiang Eddie T , Dudek Steven M , Garcia Joe G
Published: June 2021

Endothelial cytoskeleton is a contractile structure responsible for cellular responses to external stimuli and mechanical stress. Nonmuscle myosin light chain kinase (nmMLCK), a critical actin‐binding protein is required for trafficking of inflammatory cellsand alterations in permeability. c‐Abl kinase plays an essential role in barrier regulation via posttranslational modification of nmMLCK. Abl tyrosine kinase phosphorylates nmMLCK and regulates endothelial barrier function. We hypothesized that tyrosine kinase inhibitor imatinib, an anticancer agent, can exacerbate lung injury induced by mechanical ventilation (MV). To explore the role of c‐Abl in lung injury in vivo, mice were tested in our ventilation‐induced acute lung injury (VILI) model after imatinib. Mice were harvested 4h after MV. Imatinib significantly increased bronchoalveolar lavage protein levels (825ug/ml) and total inflammatory cell counts (1.07 × 10□) compared to sham (571ug/ml, 0.75 × 10μ) (p<0.05). These preliminary results indicate that imatinib exacerbates VILI‐injury, likely via c‐Abl blockade. These studies have clinical relevance given the extensive use of imatinib as an anticancer agent and support an important functional role for c‐Abl in lung permeability

Funded by: NIH grant: P01 HL58064
Excretion mass balance and quantitative whole‐body autoradiography following a single oral (PO) administration of [14C]MSDC 0602, an mTOT‐modulating insulin sensitizer, in Sprague Dawley (SD) and Long‐Evans (LE) rats
Authors: Adams Wade J. , Colca Jerry R. , Lordi Alfred W. , Solon Eric G.
Published: June 2021

The objectives of this study were to determine the mass balance excretion, plasma pharmacokinetics and tissue distribution of radioactivity following PO administration of [14C]MSDC‐0602 in rats. Five groups of male SD rats and 1 group of male LE rats (28 total rats) that weighed approximately 250 g were dosed. All rats were administered a single PO bolus of [14C]MSDC‐0602 as a suspension at a dose of 10 mg/kg (50 μCi/kg). Excretion of radioactivity was rapid, with the majority eliminated within 24 h post‐dose. Biliary excretion was the primary route of elimination in bile duct‐cannulated (BDC) rats. Total recovery in urine and bile in BDC rats suggested the extent of oral absorption was at least 60%. Urinary recovery of radioactivity from intact rats (22.4%) was higher than in BDC rats (12.3%), and total radioactivity recovered in feces (31.7%) and bile (48.1%) was higher in the BDC rats (79.8%) than in the feces of intact rats (67.0%), suggesting enterohepatic recirculation of radioactivity. Plasma radioactivity had a Tmax of 8 h and declined with a t1/2 of 14.6 h. [14C]MSDC‐0602‐derived radioactivity was widely distributed; tissues levels were lower than blood through 192 h post‐dose in LE rats.
Simvastatin but not pravastatin reduces the hypertensive response to intracerebroventricularly infused angiotensin II
Authors: Ufnal Marcin , Drapala Adrian , Sikora Mariusz , Skrzypecki Janusz
Published: June 2021

Several lines of evidence suggest that beneficial effects of statins may depend in part on their interaction with angiotensin peptides. For example, recently we have found that simvastatin reduces the hypertensive response to intracerebroventricularly (icv) infused angiotensin II (Ang II) in rats. In the preset study, we checked whether orally given pravastatin affects the hypertensive response to icv infused Ang II in the same manner as does simvastatin. We maintained Sprague Dawley rats on either tap water (control) or water containing simvastatin or pravastatin for four weeks. Subsequently, we measured arterial blood pressure and heart rate at baseline and after icv infusions of Ang II. We found no significant difference between the groups in mean arterial blood pressure (MABP) and heart rate at baseline. ICV infusion of 10 ng of Ang II caused a significant increase in MABP in all the groups. Rats treated with simvastatin showed significantly smaller hypertensive responses to icv Ang II than controls and pravastatin treated rats. In conclusion, the study shows that simvastatin but not pravastatin affects the hypertensive response to icv infused Ang II. These may be caused by differences in penetration through the blood‐brain barrier between the statins and their metabolites. The study was supported by the Polish Ministry of Science and Higher Education, Iuventus plus grant.
Influence of a short‐term increase in pressure, with and without recovery, on flow‐induced dilation in aged soleus muscle feed arteries (SFA)
Authors: Seawright John , Woodman Christopher R.
Published: June 2021

We tested the hypothesis that a short‐term increase in intraluminal pressure, to mimic a bout of exercise, would attenuate age‐induced impairments in flow‐induced dilation in SFA and that improved endothelial function would persist after a 2 h recovery period. SFA were isolated from young (4 mo) and old (24 mo) Fischer 344 rats. SFA were cannulated and pressurized at 90 (p90) or 130 (p130) cm H2O for 1 h. At the end of the 1 h treatment period, p130 SFA were lowered to 90 cm H2O and flow‐induced dilation was assessed. In a separate group of SFA, pressure was raised to 130 cm H2O for 1 h and subsequently lowered to 90 cm H2O for 2 h. Flow‐induced dilation was significantly blunted in old SFA relative to young SFA. Pre‐treatment with increased pressure for 1 h improved flow‐induced dilation in old (not young) SFA. The beneficial effect of pressure was not apparent after 2 h recovery. To determine the role of nitric oxide (NO) in pressure treated SFA, flow‐induced dilation was assessed in the presence of a NOS inhibitor (L‐NNA). Results indicate that the beneficial effect of pressure on flow‐induced dilation in old SFA was abolished in the presence of L‐NNA. These results indicate that a short‐term increase in intraluminal pressure, to mimic a bout of exercise, improves NO‐mediated endothelium‐dependent dilation in old SFA; however, the beneficial effect of pressure is not apparent after 2 h recovery.

Research supported by AHA grant 4150031 (CRW), and a Huffines Institute of Sports Medicine Graduate Student Research Grant (JWS).
Cardiomyocyte Cell Cycle Activity and Nucleation in the Regenerating Giant Danio Heart
Authors: Lala Tanmoy Das , Haag Maria T , Lafontant Pascal J
Published: June 2021

Studies to date suggest that regeneration of the zebrafish heart after apical resection is supported by the proliferation of de‐differentiated cardiac myocytes (CMs). We developed a model of heart regeneration in response to cautery injury in Giant danio (GD), a closely related species to the zebrafish. We have previously shown that robust 5‐EDU incorporation in MEF‐positive cells in the regenerating compact heart and adjacent trabeculae, indicative of cell cycle re‐entry in CMs. Here we demonstrate by transmission electron microscopy that partially differentiated and mitotic CMs are present in the regenerating myocardium. To determine whether mitotic CMs proceeds through both karyokinesis and cytokinesis, we have performed nucleation studies on isolated CMs following enzymatic digestion. A sampling of 5000 CMs revealed an absence of bi‐nucleated cells in control or fully regenerated hearts, suggesting that cell cycle activity results in both karyokinesis and cytokinesis and the formation of new mono‐nucleated CMs, as opposed to the karyokinesis without cytokinesis reported in sub‐populations of adult mammalian ventricular CMs. Taken together, our data suggest that mono‐nucleation may be the terminal state of CMs in non‐injured and fully regenerated fish ventricular myocardium.
STUDY OF THE EFFECT OF CHRONIC CHOLINERGIC STIMULATION WITH PYRIDOSTIGMINE BROMIDE ON CARDIOVASCULAR AUTONOMIC CONTROL IN SPONTANEOUSLY HYPERTENSIVE RATS (SHR)
Authors: BLANCO JOAO HENRIQUE DUTRA , SOUZA HUGO CELSO DUTRA
Published: June 2021

We investigated in spontaneously hypertensive rats (SHR) the effect of chronic inhibition of acetylcholinesterase (AChE) with pyridostigmine bromide (PYR) on the autonomic cardiovascular control. Fourteen male SHR (22 weeks old) were divided into 2 groups: SHR‐Control and SHR‐PYR (treated with PYR dissolved in drinking water (~30mg/Kg/day) for 2 weeks). The autonomic control was investigated by using different approaches: 1) double blockade with methylatropine and propranolol, 2) baroreflex sensibility (BRS) with phenylephrine and nitroprussite and 3) autonomic modulation of heart rate variability (HRV) and the systolic blood pressure variability (SBPV).

Treatment with PYR reduced the mean blood pressure (BP) and heart rate (HR) compared to control animals (141±3 vs. 151±2 mmHg and 322±6 vs. 355±5 bpm). Regarding the autonomic control, treatment with PYR promoted the following effects; increase in cardiac vagal tone (72±10 vs. 36±7 bpm); increase in BRS for the tachycardic responses (2.74±0.15 vs. 0.81±0.11 bpm/mmHg); and reduction in low frequency oscillations of SBPV (3±0.4 vs. 5.4±0.4 mmHg2).

Our results show that treatment with PYR in hypertensive rats promote reduction in BP and HR associated with improvement of cardiac autonomic control assessed by different approaches.

Grants: FAPESP 2011/22513‐4.
Isolation and Surface Characterization of Mesenchymal Stem Cells(MSCs) Derived From Term Human Amnion
Authors: Ren Yuexin , Stabila Joan P , Kurihara Itsuka , Morgan Jeffrey Y , Aaron Roy K , Padbury James
Published: June 2021

Objective

Articular cartilage damage has a very low spontaneous healing capacity. Emerging evidence suggests human placental membrane is a valuable source of MSCs for cell‐based therapy to promote articular cartilage repair. However, the identification of MSC has been hampered. Thus there is a clear need to develop strategies leading to the identification of potential MSC markers. The objective of this study was to isolate and characterize the cell populations derived from term pregnancy human amnion.

Methods

Cells were isolated from amnion membranes from patients at gestational weeks 39±1. Flow cytometry analysis was performed with the cells. Direct conjugated Ab used for flow cytometry included anti‐CD44‐FITC, CD73‐FITC, CD105‐FITC, CD45‐PerCP, CD90‐PerCP, CD11b‐PE, CD29‐PE, CD34‐PE. Analysis was performed with FlowJo software.

Results

The positive markers in isolated cell populations on Day 0 were CD14, CD11b, CD29, CD44, CD45, CD90, CD105. After 10 days culturing in expansion medium, the macrophage marker CD14 disappeared and mesenchymal stem cell markers (CD29, CD44, CD90, CD73, CD105) were demonstrated increased expression levels. Throughout, the cells were negative for markers of developmental stages of blood cells(CD11b, CD45).

Conclusion

Our results indicate that MSCs can be isolated from the human term placental membranes. The human amniotic MSCs maintained a marker profile similar to the mesenchymal progenitors and could be used for studies as an alternative source of MSCs for further application in cell‐based therapies.
Expression of Membrane Raft‐Associated Proteins During Mechanical Injury of 1321N1 Human Astrocytoma Cells
Authors: Martinez Namyr Antonio , Ayala Alondra M , Martinez Magdiel , Silva Walter I
Published: June 2021

Glial cells (GC) are the most abundant cellular element in the nervous system. Astrocytes have gained prominence as mediators of acute and persistent inflammatory reactions in the CNS, such as those occuring after spinal cord injury and Alzheimer's disease (AD). GC responses can be both protective and degenerative in nature, depending on their spatiotemporal chemical environment. Thus, understanding reactive gliosis and the molecular mechanisms underlying these responses, and what promotes their glioprotective roles is imperative. Therefore, we have implemented the use of an in vitro Mechanical Strain Injury Model System using 1321N1 human astrocytoma cells. The stable expression of the P2Y2 nucleotide receptor in normally P2‐devoid 1321N1 cells promotes cell survival. Also, data suggests that this receptor interacts with the membrane‐raft protein cav‐1 during signaling/trafficking. Furthermore, the late‐onset AD marker protein sorLA, has also been shown to be a partner of cav‐1 in glia. Therefore, we have hypothesized that the glioprotective actions of both P2Y2 and sorLA are intimately linked to their expression and trafficking via cav‐1 positive membrane rafts micro domains. NAM is supported by the NIGMS‐MBRS‐RISE Program GM61838 at the UPR‐MSC.
In vivo ablation of promyelocytic leukemia (PML) tumor suppressor protein leads to behavioral changes in mice
Authors: Martinez Luis Alberto , Tejada-Simon Maria Victoria
Published: June 2021

The promyelocytic leukemia protein (PML) is a tumor suppressor factor primarily known for its involvement in acute promyelocytic leukemia (APL). Prospective studies of PML in the brain are sparse. However, recent studies have provided evidence that in the central nervous system PML participates in neurogenesis. To further understand the role of PML in the mammalian brain, we studied plasticity and behavioral changes in a PML knockout mouse. If PML is involved in neurogenesis, an important process for proper brain development as well as learning and memory functions, we hypothesized that PML might have a role in plasticity and cognition by regulating neuronal development. Behavioral studies demonstrated that PML knockout mice present abnormalities in conditioned learning and spatial memory, as determined by fear conditioning and Morris water maze tasks, respectively. Additional behavior anomalies were revealed during tests which measure anxiety, with PML knockout mice exhibiting less anxiety, locomotion and hyperactivity. Finally, impairments in hippocampus‐dependent learning were mirrored by altered long‐term plasticity at Schaffer collateral‐CA1 synapses. Therefore, we provide evidence for a novel and important role of PML, beyond cell proliferation, where it contributes to synaptic plasticity and associated behavioral processes.
Voluntary wheel‐running improves metabolic flexibility in the liver
Authors: Kearney Monica L. , Morris E. Matthew , Meers Grace M. , Fletcher Justin A. , Thyfault John P.
Published: June 2021

Hepatic metabolic flexibility, the capacity to change substrate utilization, may be important for protection against hepatic steatosis. To examine whether increased physical activity improves substrate switching in liver mitochondria, age‐matched male Sprague‐Dawley rats underwent 4 weeks of voluntary wheel‐running (WR; n=4) or remained sedentary (SED; n=4) prior to sacrifice at 16 weeks. At sacrifice, there was a trend towards lower body weight in WR compared to SED, but food intake and intake per body weight were not different between groups over the 4 weeks. Isolated hepatic mitochondria were analyzed for fatty acid oxidation (FAO) with and without addition of 1 mM pyruvate, and pyruvate oxidation (PyvOx) with and without addition of 200 μM palmitate. Complete FAO (14C palmitate to 14CO2) was higher in WR compared to SED (4.29 ± 0.05 vs. 3.01 ± 0.11 nmol/g/h; p < 0.05), and the amount of FAO inhibited by pyruvate was 2 fold higher in WR vs. SED (1.74 ± 0.19 vs.0.82 ± 0.23 nmol/g/h; p < 0.05). Furthermore, the amount of complete PyvOx (14C pyruvate to 14CO2) inhibited by palmitate in mitochondria was 25% higher in WR compared to SED (41.57 ± 0.04 vs.31.24 ± 0.09 nmol/g/h; p < 0.05). Thus, higher daily physical activity results in greater substrate‐switching and metabolic flexibility in hepatic mitochondria.

Support: NIH R01DK088940
Skeletal muscle as a possible compartment for the sequestering of Doxorubicin following administration
Authors: Fabris Sergio Antonio , Chenard Pamela , MacLean David
Published: June 2021

Doxorubicin (DOX) is an anti‐cancer chemotherapeutic and although widely used, its accumulation over time in skeletal muscle tissue has attracted little attention. The purpose of this research was to study intracellular DOX concentrations in skeletal muscle following its administration in the rat. A bolus injection of 1.5 and 4.5 mg/kg of DOX was administered intraperitoneally in Sprague Dawley rats, and medial gastrocnemius samples were collected 24 and 96 hrs post injection. Intramuscular DOX concentrations were elevated (P<0.05) as compared to control at all time points. Following the 1.5 and 4.5 mg/kg dose, intramuscular concentrations decreased (P<0.05) from 0.24±0.05 and 0.83±0.18 nmol/g at 24 hrs to 0.04±0.01 and 0.40±0.10 nmol/g at 96 hrs, respectively. Although there was a decrease in the intramuscular concentration of DOX over time, these levels remained higher (P<0.05) in the 4.5 mg/kg rats as compared to those administered the 1.5 mg/kg dose. Interestingly, at the lower dose, the intramuscular DOX levels had decreased 83% between 24–96 hrs, while at the larger dose this decrease was only 52%. These data clearly demonstrate that DOX accumulates in skeletal muscle in a dose dependant manner. Furthermore, it appears that the rate of removal or degradation of the intramuscular DOX is slower at increasing doses. These findings have clinical implications as skeletal muscle may be an important compartment for the sequestering of DOX from the circulation, hence limiting its therapeutic impact. This intramuscular accumulation may also have an effect on long‐term function as its metabolite has been shown to be cytotoxic.

Supported by NSERC.
The Effects of Aging on AMPK Subunit Expression and Complex Formation
Authors: Hall Derrick E. , Hardman Shalene E. , Jacobs Matthew B. , Mitchell Alyssa J. , Thomson David M.
Published: June 2021

AMP‐activated protein kinase (AMPK) is an important energy sensor in skeletal muscle. Many of the processes it regulates have been shown to be disrupted with aging. AMPK functions as heterotrimeric complex. The purpose of this study was to determine whether changes in the subunit composition of AMPK occur in aged skeletal muscle.. We studied gastrocnemius muscles from young adult (8 mo) and old (30 mo) male Fischer344 x Brown Norway F1 hybrid rats (n = 7–8/group). Immunoprecipitation (IP) of the catalytic AMPK α1 and α2 isoforms was followed by detection of associated β1, β2 and γ3 subunits by immunoblot. Protein levels for the β and γ isoforms were normalized to the corresponding α subunit with which they were immunoprecipitated. There was a 128% increase (p < 0.05) in the immunoprecipitated α1 subunit with age, accompanied by a 36% decrease in α2. There was a 59% decrease in β1 associated with α1 with age. No significant changes in β2 associated with α1, or in β1 or β2 associated with α2 were noted. AMPK γ3 association with α1 was decreased by 93% and with α2 by 83% with age. In conclusion, aging leads to a switch in AMPK subunit content and heterotrimer composition. Funding: NIAMSD Grant AR‐51928.
Effectiveness of humor on short term memory function in elderly subjects
Authors: Bains Gurinder Singh , Berk Lee , Deshpande Pooja , Pawar Prema , Daher Noha , Lohman Everett , Petrofsky Jerrold , Schwab Ernie
Published: June 2021

With ageing, the damaging effects of stress can impair the ability to learn and sustain memory. The purpose of this pilot study was to examine the effect of watching a humor video on short term memory in the elderly. Humor and the associated mirthful laughter can reduce stress by decreasing stress hormones, cortisol and catecholamines. Excess cortisol can damage hippocampus neurons leading to impairment of learning and memory. The standardized neuropsychological memory assessment tool, Rey Auditory Verbal Learning Test (RAVLT) was used to assess for 1) learning ability, 2) delayed recall ability, and 3) delayed visual recognition ability. RAVLT was given to 10 elderly individuals (average age 74.0 ± 11.7 years) before and after watching a humor video of their choice for 30 minutes. For learning ability, we conducted 5 trials with average performance scores. Results from the Wilcoxon Signed Ranks Test showed that humor with resultant mirthful laughter increased the ability to learn, recall, and recognize. Following the watching of the humor video: 1) learning ability improved by 19.4% (p=.003); 2) delayed recall improved by 33.3% (p=.004); 3) and visual recognition increased by 21.4% (p=.006). In conclusion, elderly individuals’ watching a humor video that induces mirthful laughter can enhance: 1) capability to learn, 2) have greater recall, and 3) improve visual recognition in short term memory function.
Biochemical and functional characterization of Mgm101, a Rad52‐type recombination protein in mitochondria
Authors: Mbantenkhu MacMillan K , Wang Xiowen , Nardozzi Jonathan D , Wilkens Stephan , Chen Xin Jie
Published: June 2021

Homologous recombination (HR), an error free DNA repair mechanism, is poorly understood in mitochondria. This mechanism, evolutionarily conserved from bacteriophage to humans, has evolved primarily as a strategy for the repair of DNA double strand breaks. The recombinational repair of double strand DNA breaks may proceed by two distinct pathways. The conventional pathway requires a RecA/Rad51‐type recombinase that catalyzes strand invasion. The alternative pathway involves the Rad52‐type proteins, which promote recombination by single strand annealing. The Rad52‐type recombination proteins inherently form rings and filaments in vitro. The functional implications of these higher order structural organizations are not fully understood. We have recently shown that the mitochondrial genome maintenance protein, Mgm101, is a homologue of Rad52‐type recombination proteins. Like Rad52, Mgm101 forms rings. Loss of function mutations were identified that affect ring stability. Here, we show that the C‐tail, which is rich in conserved basic and aromatic residues, is unique to Mgm101 orthologues. We show that the residues K253, W257, R259, Y268 and the triple mutant K251A‐K253A are critical for function. Additionally, we show by size exclusion that these conserved residues fall into two categories: those that destabilize the ring structure of Mgm101 and those that do not. Our data support the idea that the Mgm101 C‐tail may represent a novel functional module for catalyzing DNA recombination. The biochemical characterization of these mutant proteins will shed light on the mechanism of mtDNA recombination. This work was supported by the grant R01AG023731 from the National Institute on Aging/NIH.
Mid‐Career Adventure: Making a Successful Transition
Authors: Koen Deb
Published: June 2021

“Life is either a daring adventure or nothing.” Helen Keller

Whether your mid‐career transition is driven by a deeper calling, a negative situation, or simply curiosity about what else you might become, why not make your transition an adventure? Although most people change careers—some many times‐‐ over the course of their professional lives, the path forward is not always easy or obvious.

Transitions can be significantly enhanced with a sound strategy and a spirit of adventure. If you're considering a dramatic change or even dabbling in minor adjustments, this talk will offer a framework for successful transition.

These success strategies will allow you to immediately begin to: discover your motivators, generate options within the realm of science and beyond, overcome barriers, and develop a focused plan for your future.
Maternal DHA supplementation during pregnancy and plasma lipids and glucose levels in offspring at age 4y: follow‐up of a randomized controlled trial
Authors: Gutierrez‐Gomez Yareni Yunuen , Ramakrishnan Usha , Stein Aryeh D. , Martorell Reynaldo , Aguilar‐Salinas Carlos , Romieu Isabell , Rivera Juan A.
Published: June 2021

Little is known about the effects of prenatal docosahexaenoic acid (DHA) supplementation on offspring lipid and glucose metabolism. We investigated the effect of maternal DHA supplementation during pregnancy on offspring plasma lipid and glucose levels at age 4 y. In a double‐blind, randomized, controlled trial conducted in Mexico, pregnant women were supplemented daily with 400 mg DHA or placebo from 18–22 wk gestation to parturition. Offspring of the women who participated in this study are being followed; at age 4 y non‐fasting blood samples, were obtained from 524 children (53.9% of the birth cohort). We assessed total cholesterol (TC; mean ±SD 157.9 ±25.3mg/dl); LDL‐C (83.0 ±21.9mg/dl); HDL‐C (51.7 ±10.1mg/dl); Apo B (76.9 ±15.2mg/dl); triglycerides (122.1 ±67.4mg/dl); glucose (93.7 ±10.9mg/dl) and insulin (9.7 ±11.2μU/ml). Between‐group differences (DHA ‐ placebo), adjusted for maternal height and time since last food intake, were: TC, 1.73 mg/dl (95% CI −2.63, 6.09); LDL‐C, 1.62 mg/dl (0.24, 1.42); HDL‐C, 0.66 mg/dl (−1.07, 2.39); Apo B, −0.15 mg/dl (−2.78, 2.48); triglycerides −0.15 mg/dl (−11.50, 11.21); glucose −0.99 mg/dl (−2.86, 0.88); insulin −0.18 μU/ml (− 2.08, 1.7). In this study, prenatal DHA supplementation did not impact on lipids and glucose markers in early childhood.

Funded by NIH (HD043099)
Leptin and resistin are influenced by increased body fat measurements in pregnant women
Authors: Ozias Marlies K , Li Shengqi , Lin Ping‐Chang , Schmitt Allan , Hull Holly R , Carlson Susan E
Published: June 2021

Our objective was to determine if adipokine concentrations were associated with total body fat, subcutaneous (SF) and visceral abdominal fat (VF) in obese (O) and normal weight (N) pregnant women. Plasma adipokines (leptin, adiponectin, visfatin, and resistin) were measured in 5 O and 9 N pregnant women (no pre‐eclampsia or GDM) after 35 wks gestation by EIA (Alpco Diagnostics; Phoenix Pharmaceuticals). We grouped women based on subject‐reported pre‐pregnancy weight and height. Total body fat was measured 2‐wks postpartum by iDXA (GE Healthcare). SF and VF were measured with Image J software from MRI (Siemens Skyra 3T) abdominal axial scans (5.0mm; 5.0mm gap) of vertebral L2‐S3. Statistical analyses involved t‐tests between groups and simple linear regression to compare adiposity measurements to adipokine concentrations. Leptin increased in O vs N (74 vs. 31 ng/mL, P < 0.001) and was associated with total body fat mass (r = 0.843; P < 0.001), SF (r = 0.649; P = 0.012) and VF (r = 0.618; P = 0.019). Resistin was only associated with SF (r = 0.538; P = 0.038). O women had significantly more SF (2137 vs. 706 g; P = 0.041) but not VF (290 vs. 103 g; P = 0.117) compared to N women. In pregnancy, elevated leptin concentration was associated with all measures of adiposity while resistin was only associated with SF. These findings suggest that increased leptin may be an accurate biomarker of adiposity during pregnancy.

Grant Funding Source: Sam E. and Mary F. Roberts Endowment, NICHD HD02528, NIH S10 RR029577 and UL1 TR000001
Primary cilia regulate gastrin secretion in GLUTag cells
Authors: Saqui‐Salces Milena , Merchant Juanita L.
Published: June 2021

Primary cilia (PC) are sensory organelles that we recently reported are expressed on endocrine cells of the stomach. Deletion of PC on the gastric mucosa resulted in higher plasma gastrin (Gast) levels. Therefore we hypothesized that PC on endocrine cells modulate Gast secretion. Recently we discovered that GLUTag cells present PC, in addition to expressing and releasing Gast. To define the extracellular signals regulating PC, GLUTag cells were treated with 20 mM glucose, 2% peptone, 5μM forskolin, 100 nM octreotide and 50 μM omeprazole. After 2 h tratment, PC were stained with anti‐acetylated tubulin and counted. Secreted Gast and GLP‐1 were measured and normalized to cell content. We found that glucose induced GLP‐1 but not Gast secretion and had no effect on PC. Peptone reduced PC numbers and induced Gast but not GLP‐1. Forskolin induced secretion of both hormones without affecting PC presentation. Octreotide reduced the secretion of both hormones without changing PC. However, omeprazole reduced PC numbers and increased Gast but not GLP‐1 secretion. Our data suggest that PC presentation is regulated by extracellular signals. Reduction of PC stimulated Gast secretion. PC were not associated with GLP‐1 secretion. Therefore, we concluded that GLUTag cells are a good model to study Gast release, and that PC regulate Gast but not GLP‐1 secretion. Research support: P01‐DK62041 and 5P30DK034933
Salt induced cardiac hypertrophy is blood pressure independent and prevented by Losartan and N‐acetylcysteine
Authors: Katayama Isis AKemi , Pereira Rafael Canavel , Shimizu Maria Heloísa Massola , Heimann Joel Claudio
Published: June 2021

Objective

To evaluate the mechanisms of left (LV) and right (RV) ventricular hypertrophy induced by high salt intake.

Methods

Wistar rats were fed normal (NS1.3% NaCl) or high (HS 8%) salt diet since weaning. From the 7th week of age, 3 HS subgroups received hydralazine, losartan or N‐acetylcysteine (HZ 15 and LOS 20mg/kg/day and NAC 600mg/l). Tail blood pressure (BP), food intake (FI), cardiac mass to tibial length ratio (CM/TL), cardiomyocyte transverse diameter (TD) in both ventricles and myocardial TBARS were measured.

Results (n=8/group):

NS
HS
HS+HZ
HS+LOS
HS+NAC

BP (mmHg)
110.7± 1.6a
143.1± 4.0b
116.4± 1.8a
116.5± 1.6a
166.8± 1.6c

FI (g/day)
16.6±1.85 a
15.7±0.91 a
14.3±0.59 a
16.5±0.98 a
23.7±0.63 a

CM/TL (g/cm)
0.34±0.01a
0.51±0.02b
0.47±0.02b
0.38±0.01a
0.44±0.00c

TD – LV (μm)
12.5±0.47a
19.6±0.44b
18.9±0.76b
13.2±0.33a
15.9±0.75c

TD – RV (μm)
11.8±0.32a
17.7±0.56b
16.4±0.71b
11.9±0.45a
12.8±0.41a

TBARS (nmol/mg/ml)
0.78±0.27 a
2.57±0.38 b
2.75±0.75 b
2.65±0.32 b
0.89±0.09 a

Data are reported as mean±SEM. Means in row with superscripts without a common letter differ, P<0.05

Conclusions

In Wistar rats, LOS prevented cardiac hypertrophy induced by high salt intake. It can be speculated that this result is an AT1 receptor‐dependent mechanism. However, NAC partially prevented the cardiac hypertrophy, suggesting that oxidative stress also could be involved on this process.

Supported by FAPESP and CNPq.
Diverse Effects of Aging on the Cardiac Response in Pathological Left Ventricular Remodeling and Dysfunction
Authors: de Boer Martine , van Deel Elza D. , de Kleijnen Marion , Hoeijmakers Jan H.J. , Duncker Dirk J.
Published: June 2021

The aging heart undergoes structural and functional changes that are reminiscent of the failing heart, and which thus may increase cardiac vulnerability to develop heart failure. To test this hypothesis, we subjected mice to pressure overload by transverse aortic constriction (TAC) or myocardial infarction (MI) at 3, 12 and 24 months of age. Eight weeks after TAC or MI, left ventricular (LV) geometry and function were measured. Aging mildly affected cardiac geometry and function in sham operated animals. TAC produced marked LV hypertrophy, cardiac dysfunction, pulmonary congestion and right ventricular (RV) hypertrophy in all age groups. MI produced LV dilation, cardiac dysfunction and LV and RV hypertrophy in all age groups. Interestingly, the hypertrophic responses to TAC and MI were diminished with aging, but whereas the blunted hypertrophic response in TAC was associated with aggravated LV dysfunction, LV function tended to improve in MI. Thus, aging aggravated the TAC‐induced decrease in LV dP/dtP40 and LV dP/dtmin and the increase in lung fluid and RV weight in the 24 vs. 3 months old mice. In contrast, MI‐induced diastolic dysfunction was slightly blunted with aging as demonstrated by decreases in tau and LV end diastolic pressure in the 24 vs. 3 months old mice. These observations indicate that the effects of aging on the cardiac response to hemodynamic overload depend critically on the underlying pathology.

Supported by a NHF Grant 2007B024
The role of valproic acid (VPA) in regulating ischemia‐induced plasma extravasation into the peritoneum: implications for abdominal adhesion formation
Authors: Brady Matthew , King Elizabeth , Heydrick Stanley , Stucchi Arthur F
Published: June 2021

Postoperative adhesions are a significant healthcare problem, occurring in over 94% of patients following abdominopelvic operations. Our lab showed that VPA reduces adhesion formation in a rat ischemic peritoneal button model; however its mechanism of action remains unknown. We proposed that VPA may blunt peritoneal plasma extravasation and reduce fibrin, the precursor of adhesions. This study aimed to create a method to quantify extravasation to test this hypothesis. Rats (n=11) underwent laparotomy and ischemic button creation. Animals received either intraperitoneal saline or VPA (50mg/kg) intraoperatively, followed by Evans Blue (25mg/kg) via tail vein injection. At 24 hr, plasma, ischemic button, and peritoneal tissue were collected. Evans Blue was extracted from tissue and its content was quantified by spectrophotometry. Plasma extravasation was increased in ischemic buttons compared with non‐ischemic inflamed peritoneal tissue in both groups (1.399uL/mg ±0 .086 vs. 0.288uL/mg ± 0.079, p<0.001) validating the model; however, VPA did not reduce plasma extravasation into peritoneal sidewalls, ischemic buttons, or peritoneal fluid when compared with control. Our data demonstrates that ischemia‐induced extravasation of plasma contents appears to be the primary source of peritoneal fibrin. Funded by Cooper‐Tyler Endowment, Department of Surgery, Boston University Medical Center.
Characterizing the co‐occurrence between mitochondrial KATP channel and uncoupling proteins in type 2 diabetes
Authors: Brito Alfonso , Peltekian Lila , Mandala Sridhar , Gonzalez Nelson , Lopez Vanessa , Yamazaki Katrina
Published: June 2021

Patients with type 2 diabetes (T2D) have a heightened risk of developing heart failure due to mitochondrial abnormalities and sporadic cardiac energy metabolism. The main objective of this project is to determine mitochondrial KATP channel dysfunction and UCP‐2 expression relative to each other utilizing an in vivo rat model of T2D. Administration of epicatehin, a cocoa flavanol, was tested for cardioprotection in T2D. Results demonstrated that diabetic animals had significant increases in body weight and blood glucose levels, while EPI treatment had changes similar to sham animals. Western analysis show an overall decrease in mitochondrial proteins in diabetic animals, whereas EPI treated animals maintained levels close to sham animals. Further work will be done to evaluate mitochondrial KATP channel function and UCP expression. We expect that diabetic animals will have increased mitochondrial KATP channel dysfunction and increased UCP expression representing an overall drop in mitochondrial function. These results will provide evidence for the co‐occurrence of mitochondrial KATP channel dysfunction and UCP overexpression along with a possible treatment to prevent the progression of T2D.
VPT‐60: A novel approach to monitoring peripheral nerve sensitivity
Authors: Blackburn Mollie , Gibson Janelle , Breen Paul , Latman N. S.
Published: June 2021

Peripheral nerve sensitivity (PNS) can be used as an indicator of nerve loss or damage known as peripheral neuropathy. Because peripheral neuropathy can result in morbidity and mortality, accurate monitoring of PNS is imperative.

A review of the literature has shown that variables such as age, sex, compression force and temperature can effect PNS. Neither of the two clinical reference standards [Semmes‐Weinstein Monofilaments (SWM) or Bio‐Thesiometer (BT)] take these variables into account in determining PNS.

We developed a novel instrument, VPT‐60, that measures PNS, temperature and compression force of a digit. It can vary the frequency of vibration and the rate of amplitude change among other variables.

The correlation of these variables with PNS was analyzed in 41 subjects that exhibited a wide range of characteristics. We found a statistically significant correlation coefficient between VPT‐60 PNS and age [0.52 (p=0.001)]; sex [0.33 (p=0.03)]; finger weight [−0.045 (p=0.005)]; and finger temperature [0.34 (p=0.03)]. While the VPT‐60 had a significant correlation with both the SWM (0.75) and the BT (0.86), the BT correlation with SWM was only 0.51. At 60 Hz vibration, the VPT‐60 had a higher correlation with SWM than did the BT at 120 Hz.

In this study, the VPT‐60 appeared to provide a better approach to determining peripheral nerve sensitivity and the factors that effect it than the SWM or BT.
Optically transparent and permeable microarrays for cellular assays
Authors: Gaborski Thomas , Busse Katelyn , Miller Joshua , Wilcox Jascha
Published: June 2021

A new class of porous membrane, porous nanocrystalline silicon (pnc‐Si), offers a unique combination of nanoscale thickness (< 100 nm) and tunable pore sizes in the range of 5 to 100 nm. Pnc‐Si is ideally suited for small volume cell culture devices because the nanometer thinness and high permeability enable rapid diffusion of low abundance species with minimal loss. Two cell types can be cultured within tens of nanometers of one another, allowing cell‐cell communication and other microenvironment‐dependent co‐culture studies. We have developed an approach to create microwells on these suspended membranes using photopolymerized PEG. Cells grown within these microwells are spatially separated, but can readily communicate through the membrane with a feeder cell layer or with neighboring microwells due to PEG permeability. Additionally, pnc‐Si membranes are extraordinarily transparent to light, permitting their use in image‐based, high‐content screening assays. Sources of Funding: NIH and RIT.
US adults and adherence to the Dietary Guidelines for Americans (DGA)
Authors: Troy Lisa M , Dwyer Johanna , Jacques Paul
Published: June 2021

We examined adherence to the DGA in the Framingham Heart Study Offspring at exam 5 (1991–1995) and over a decade later at exam 8 (2005–2008). The 2010 Dietary Guidelines for Americans Index (DGAI_2010) measures adherence to the key dietary recommendations of the 2010 DGA. The DGAI_2010 is a continuous score (range 0–100), a higher score indicates greater adherence to the DGA. Means and t‐test were used to examine differences in DGAI_2010 scores between the two exams. At exam 5 Offspring participants with complete dietary data (n=3330) had a mean age of 58.2 years (range 19.7 to 87), and a mean BMI of 27.4 kg/m2 (range, 14.4 to 53.7). Fifty‐three percent were women, 19% smoked regularly, and 27.6% took multivitamins. A decade later, Offspring (n=2642) had a mean age of 66.3 years (range 40 to 92), and a mean BMI of 28.2 kg/m2 (range, 13.8 to 56.4). Fifty‐five percent were women, 8.5% smoked regularly, and 60% took multivitamins. We observed a modest but significant difference in adherence to the DGA between the two time periods. At exam 5 the DGAI_2010 median=58.2 (range 19.7 to 87.0) and at exam 8 DGAI_2010 = 59.8 (24.1 to 85.5) (P<0.001). Restricting the analysis to participants with valid dietary data at both exams (n=2302) did not materially change the results. Dietary improvements as measured by adherence to the DGA were observed in U.S. adults.
The Sydney Diet Heart Study: a randomised controlled trial of linoleic acid for secondary prevention of coronary heart disease and death
Authors: Ramsden Christopher E , Zamora Daisy , Faurot Kim , Majchrzak Sharon , Hibbeln Joseph
Published: June 2021

Objective

To evaluate the effectiveness of replacing saturated fat (SFA) with omega‐6 linoleic acid (LA) for the secondary prevention of coronary heart disease (CHD) and death.

Background

Advice to substitute polyunsaturated fats (PUFAs) for SFA is a cornerstone of dietary guidelines. However, clinical CHD benefits of the most abundant PUFA, omega‐6 LA have not been established. A complete analysis of the effects of LA on CHD and CVD mortality has not previously been possible due to missing data from the Sydney Diet Heart Study (SDHS). We recovered the original SDHS dataset to fill two key evidence gaps by (1) reporting unpublished CHD and CVD mortality outcomes, and (2) updating our incomplete 2010 meta‐analysis of LA intervention trials.

Design

Randomised controlled trial in 458 men with CHD.

Interventions

The intervention group replaced SFA with LA from safflower oil and safflower oil polyunsaturated margarine. The control group continued their habitual diet.

Results

The intervention group had higher all‐cause (HR 1.62; 95%CI 1.00–2.64; p=0.051), CVD (HR 1.70; 95%CI 1.03–2.80; p=0.037) and CHD mortality (HR 1.74; 95%CI 1.04–2.92; p=0.036). An updated meta‐analysis of LA intervention trials showed concordant unfavorable effects for CHD and CVD death.

Conclusions

Substituting LA in place of SFA increased all‐cause, CVD and CHD mortality. Advice to increase LA or unspecified PUFAs merits reconsideration.

Support:

NIAAA
Dietary carotenoids may reduce testicular steroidogenesis through HMG‐CoA reductase in mice with altered carotenoid metabolism
Authors: Smith Josh , Ford Nikki , Clinton Steven K , Erdman John W
Published: June 2021

Higher serum levels of lycopene are inversely associated with prostate cancer incidence. Previous work in our lab has demonstrated that, in mice lacking carotene‐15,15′‐ monooxygenase (CMO1), dietary tomato powder or lycopene reduces testicular and serum testosterone levels. We hypothesized that lycopene may reduce testicular steroidogenesis through HMG‐CoA reductase (HMGCoAr). Nine‐ to twelve‐week‐old male wild‐type (WT), CMO1−/−, and carotene‐9′,10′‐monooxygenase knockout (CMO2−/−) mice were fed AIN‐93G‐based diets containing 10% tomato powder (TP), lycopene beadlets matched for lycopene content (LYC), or control diets for four days. We examined testicular mRNA and protein expression of canonical steroidogenic enzymes and found no alterations which explained the observed hormonal changes. However, protein levels of HMGCoAr were significantly decreased (p<0.05) in WT and CMO1−/− mice fed TP or LYC, but not in CMO2−/− mice. HMGCoAr mRNA expression was unaltered, suggesting that control is through a post‐transcriptional mechanism. We also examined mRNA expression of a testicular cholesterol acquisition mediator, SR‐B1, and found no changes. In summary, LYC and TP decreased testicular HMGCoAr protein levels in a CMO2‐ dependent manner, suggesting that metabolites of lycopene or other tomato carotenoids, produced by CMO2 cleavage, may mediate this effect.

Grant Funding Source: NIH grant PHS‐1‐RO1 CA125384
Association of fat distribution with changes in bone outcomes in young girls
Authors: Laddu Deepika , Lee Vinson R , Blew Robert M , Going Scott B
Published: June 2021

Background

Childhood obesity may impair bone growth but the relationship remains unclear.

Objective

Examine longitudinal associations between total body fat (TBF), android fat (AF), and skeletal muscle fat (SMF) content, with bone outcomes in 260 girls aged 8–13y.

Methods

Peripheral quantitative computed tomography measured changes in bone strength index (BSI, mg2/mm4), strength‐strain index (SSI, mm3) and volumetric bone density (vBMD, mg/cm3) at distal metaphyseal and diaphyseal regions of the femur (fem) and tibia (tib), and baseline calf (CMD) and thigh (TMD) muscle density (mg/cm3), an index of SMF content. Baseline TBF and AF were assessed by dual‐energy X‐ray absorptiometry.

Results

TBF and AF were positively associated with fem BSI (r=0.193; r=0.174), tib SSI (r=0.184; r=0.142), and fem trabecular vBMD (r=0.196; r=0.203), and inversely associated with tib cortical vBMD (r= −0.146; r= −0.172). Lower CMD and TMD was associated with fem BSI (r= −0.222; r= −0.145), tib BSI (r= −0.193; r= −0.128), fem tot vBMD (r= −0.208; r= −0.168), and trabecular vBMD (fem: r= −0.263; r= −0.192, tib: r= −0.215; r= − 0.161). CMD was significantly associated with tib SSI (r= −0.141) and tot vBMD (r= −0.130). ANCOVA showed that girls in the middle thirds of TBF and AF had higher fem and tib cortical vBMD than girls with greater TBF and AF. Greater changes in fem BSI, tot fem vBMD and fem and tib trabecular vBMD were observed in the lowest vs. highest thirds of CMD and TMD. All results were significant at p<0.05.

Conclusions

Gains in TBF or AF may negatively impact tib bone development, while increases in CMD or TMD predict greater gains in various bone outcomes.

Grant Funding Source: NIH/NICHD #HD‐050775