bluuebunny/crossref_metadata_2025 huggingface dataset:
Aortic Pulse Wave Characteristics In Postmenopausal Women With And Without A History Of Hypertensive Pregnancy
Authors: Shepherd John , Harvey Ronee , Ranadive Sushant , Miller Virginia , Joyner Michael , Barnes Jill
Published: June 2021

Hypertensive pregnancy (HP) disorders have been linked to a four‐fold increased risk for development of future cardiovascular diseases. We examined whether history of HP in postmenopausal women (N=20, 59±5 yr) influenced the risk factors for cardiovascular disease as assessed by aortic pulse wave characteristics, compared to age and parity matched controls (N=18, 60±4 yr). Non‐invasive aortic pressure waveforms were synthesized from high‐fidelity pressure waveforms obtained from SphygmoCor applanation tonometry using the radial artery. Aortic systolic and diastolic blood pressure (ASBP, ADBP), aortic augmentation index (AIx), augmented pressure (AP), aortic pulse pressure (APP), and left ventricular wasted energy (Ew) were calculated from the generated aortic pressure waveform. There were no differences in ASBP (125±4 vs. 129±4 mmHg), ADBP (79±2 vs. 81±2 mmHg), AP (17±2 vs. 17±2 mmHg), AIx (35±2 vs. 29±1%), AIx @75BPM (31±2 vs. 29±1%), Ew (3313±338 vs. 3364±432 dynes/cm2/s), between women with a history of HP vs. matched controls, respectively (P>0.05 for all). Body mass index was significantly higher in women with a history of HP (30.6±1 vs. 26.7±1 kg/m2, P<0.05), however it did not statistically influence any of the indices (P>0.05 for all). Our results suggest that postmenopausal women with a history of HP do not demonstrate elevated aortic blood pressure or altered aortic pulse wave characteristics in comparison to matched controls.

Supported by: National Institute of Aging 1P50AG044170‐01 and CTSA UL1 TR000135 and HL 118154
Impact of Ventilatory Threshold on Mycardial Work During Exercise
Authors: Armstrong Craig , Samuel Jake , Yarlett Andrew , Stöhr Eric
Published: June 2021

The primary purpose of this investigation was to examine the impact of individual ventilatory threshold (VT) on the heart during exercise. 18 healthy male participants completed a standardised incremental exercise test to voluntary fatigue (VO2max test) to identify their VT. On a separate visit, participants exercised for 6 minutes at 40% of their VO2max. We measured heart rate, blood pressure and cardiac output using echocardiography and estimated myocardial work from the product of heart rate and blood pressure (rate pressure product, RPP). Participants were assigned to the low and high VT group if exercise at 40% exceeded or fell short of their VT, respectively. We found that most parameters were not different at rest between the low and high VT group. Importantly, during exercise, RPP was significantly higher in the low VT group (p<0.01), despite a similar oxygen consumption (VO2), cardiac output, blood pressure and heart rate reserve (p>0.05). Thus, RPP was different because of heart rate, indicating an influence of the autnonomic portion of cardiovascular regulation. We conclude that VT has significant effects on myocardial work during exercise, independent of the energetic demands of the exercise effort and the overall cardiac output. Consequently, exercise prescription needs to take into account VT, in particular in vulnerable patient populations to avoid unexpected exercise strain on the heart.
Effects of Voluntary Endurance Training on Skeletal Muscle Function During and Following Doxorubicin Treatment
Authors: Hochberg Leanne , Borges Raquel , Bredahl Eric , Quinn Colin , Hydock David
Published: June 2021

Doxorubicin (DOX), an anthracycline antiobiotic, has been shown to decrease skeletal muscle function via underlying mechanisms associated with the generation of reactive oxygen species. Prior studies have shown that exercise preconditioning attenuates the myotoxic effects of DOX, but at this point, the effects of exercise during and followingDOX treatment on skeletal muscle function is unknown. The purpose of the present study, therefore, was to investigate the effects of exercise performed during and following DOX treatment on myotoxicity. Male rats were randomly assigned to the exercise (voluntary running wheels) or sedentary (normal cages) condition for 10 weeks. Animals received weekly DOX or saline injections for the first six weeks. Grip strength was measured at baseline and weekly throughout the experimental period. Sedentary animals receiving DOX had overall decreased grip strength. This overall decrease was not observed in exercise DOX animals. These results suggest that exercise during and following DOX treatment effectively mitigates adverse effects of DOX on skeletal muscle force production.
In vivo Studies of Motor Nerve Re‐growth in Adult and Old Mice Following Contraction‐induced Injury
Authors: Vasilaki Aphrodite , Sakellariou George , Kayani Anna , Jackson Malcolm , McArdle Anne
Published: June 2021

Little is known about the changes in motor neurons that occur following contraction‐induced skeletal muscle injury and regeneration, a process that is defective in muscles of old rodents and may play a major role in the development of sarcopenia. The aim of this work was to examine structural changes in motor neurons and neuromuscular junctions (NMJs) following damaging lengthening contractions and whether this process is defective in muscles of old mice. Studies were undertaken in Thy1‐YFP transgenic mice that only express YFP in neuronal cells. One extensor digitorum longus (EDL) muscle of adult and old mice was subjected to a protocol of lengthening contractions. Structural changes in NMJs as well as the loss and regrowth of peripheral motor neurons were examined by fluorescence microscopy. Muscle fiber damage and regeneration was confirmed histologically. Three days after injury, muscles from adult and old mice showed widespread necrosis. By 28 days, muscles from adult mice appeared histologically normal, whereas muscles from old mice at 28 days following damage showed multiple small atrophic fibers and fibers with central nuclei. Major disruption of the NMJs was seen at 3 days following damage in both adult and old mice, followed by re‐innervation of the muscle that was completed by 28 days in adult mice (96% of the NMJs in EDL muscles from adult mice appeared to be normal with only 2% showing full denervation), but which remained sub‐optimal in muscles of old mice. Data indicate that muscle aging influences muscle regeneration, innervation and NMJ plasticity. Supported by Research into Ageing/AgeUK.
Graded Venous Occlusion of the Lower Limbs Contributes to the Exercise Pressor Response in Healthy Humans
Authors: Cowl Andrielle , Keller‐Ross Manda , Cross Troy , Rebollo Naomi , Maria Rios Jose , Johnson Bruce , Olson Thomas
Published: June 2021

Background

Locomotor muscle group III/IV afferent feedback contributes to sympathoexcitation. Sub‐systolic lower limb occlusion may stimulate this reflex.

Purpose

To examine the cardiovascular response to lower limb venous occlusion in healthy humans during rest and exercise.

Methods

Nineteen adults (9 men, 25±5 yr; mean±SD) participated in two visits. V1: 3 min seated rest followed by randomized bilateral thigh tourniquet inflation to 20, 40, 60, 80, 100 mmHg for 2 min with 2 min deflation between occlusions. V2: Recumbent cycle ergometer exercise at 30% peak work with occlusion described in V1. We measured mean, systolic and diastolic pressure, cardiac output, heart rate, and stroke volume (MAP, SBP, DBP, CO, HR, and SV, respectively).

Results

At rest, MAP (85±18 mmHg) increased at 100 mmHg (Δ4±5, p<0.05) mediated by increased DBP (71±15 mmHg) at 100 mmHg (Δ5±4, p<0.05) with no change in SBP. During exercise, MAP (89±11 mmHg) increased at 60 (Δ7±7), 80 (Δ14±8), and 100 (Δ16±8) mmHg occlusions via increased SBP (133±22 mmHg) at 60 (Δ12±14), 80 (Δ20±13), and 100 (Δ26±13) mmHg and DBP (68±9 mmHg) at 60 (Δ5±5), 80 (Δ10±7), and 100 (Δ12±7) (p<0.05, all). Although, CO and SV did not change, HR (108±11 bpm) increased at 40 (Δ5±4), 60 (Δ8±5), 80 (Δ13±7), and 100 mmHg (Δ15±7) (p<0.05, all).

Conclusion

Stimulation of locomotor muscle group III/IV afferents via sub‐systolic occlusion contributes to cardiovascular control.
Skeletal Muscle Afferent Inhibition Improves Exercise Tolerance in Heart Failure
Authors: Keller‐Ross Manda , Carlson Alex , O'Malley Kathy , Bruhn Eric , Wolhart Sarah , Johnson Christopher , Eisenach John , Curry Timothy , Joyner Michael , Johnson Bruce , Olson Thomas
Published: June 2021

BACKGROUND

Increased activation of Group III/IV skeletal muscle afferents is suggested to play a role in exercise intolerance in heart failure (HF).

PURPOSE

The purpose of this study was to examine if skeletal muscle afferent feedback inhibition improves exercise tolerance in HF.

METHODS

8 HF patients [59±8 yr, mean±SD] participated in two randomized incremental recumbent cycling exercise sessions to peak capacity (peak oxygen consumption, VO2). Session 1: The synthetic opioid fentanyl (50 mcg), known to block afferent feedback, was injected intrathecally (INJ) in the lumbar spine (L3‐L4 intervertebral space) prior to exercise. Session 2: Participants were prepared similarly with a sham injection (placebo, PLA). Gas exchange, dyspnea and RPE were measured.

RESULTS

HF patients exercised for a longer duration (Δ3±3 min, p=0.02) and reached a higher power output (PLA:109±30 vs. INJ:128±34 W, p=0.02) with locomotor afferent inhibition. Additionally, peak VO2 was non‐significantly greater (PLA:18.7±3.3 vs. INJ:21.8±4.4 ml/kg/min, p=0.10). With INJ workload matched to peak PLA workload, RPE was reduced (PLA:18±2 vs. INJ:15±2, respectively, p=0.005) and dyspnea was lower (PLA:7.5±2 vs. INJ:4.2±1, p=0.003) with no difference in VO2 (p>0.05).

CONCLUSION

Inhibition of group III/IV locomotor muscle afferent feedback contributes to improved exercise tolerance and exertional symptoms in HF patients.
A Pilot Exercise Intervention to Enhance Fitness and Quality of Life among African American and White Colorectal Cancer Survivors
Authors: Williams Brian , Maxwell Nicholas , Cook Jennifer , Mahoney Martin , Ray Andrew
Published: June 2021

As the third most common occurring malignancy and 3rd leading cause of cancer‐related mortality, colorectal cancer (CRC) represents an important public health concern. Substantial disparities exist for CRC with elevated incidence and relative survival rate among African Americans (AA) compared to Caucasians (C).

Purpose

To determine the feasibility of recruiting AA and C subjects into a training intervention study to improve physiologic and quality of life measures.

Methods

Subjects interested in participation were sent letters describing the study, they were then called and if interested, pre‐screened over the phone prior to consenting to assess eligibility. If deemed potentially eligible based on the pre‐screening, subjects then completed two screening visits followed by twelve weeks of progressive exercise training on a cycle ergometer.

Results

Out of the 241 letters sent, AA and C subjects had a 86% (n=112) and 96.7% (n=118) attrition rate for phone screening. Of those screened, AA and C had 66.7% (n=12) and 75% (n=3) that were eligible to begin the training. After ten months of recruitment, there have been two (1.5 % of those sent letters) AA subjects that have completed the training and one C (0.8% of those sent letters) subject.

Conclusion

Subject recruitment for a twelve week intervention training study has a very high attrition rate for both AA and C. Completion of a twelve week training after recruitment may be more difficult for African Americans compared to Caucasians.
The role of skeletal muscle characteristics in the decline of VO2peak in rats
Authors: Toedebusch Ryan , Ruegsegger Gregory , Booth Frank
Published: June 2021

Maximal aerobic capacity is a strong predictor or mortality in humans and rodents. It has been established that VO2peak declines with age beginning in the 3rd decade of life in humans. There is a paucity of data examining the underlying mechanisms that may be responsible for this VO2peak decline. Organ systems that likely play significant roles include the heart, brain and skeletal muscle. The purpose of this study was to assess skeletal muscles role during the initial decline from lifetime apex‐VO2peak in rats, and to assess the ability of physical activity to modify the decline. Two groups of rats, one with access to a voluntary running wheel (WG) and one with no wheel access (NWG) underwent VO2peak testing weekly beginning at 10 weeks of age until the end of the study. Voluntary wheel running began at 5‐weeks of age and peaked at 10‐weeks of age. Lifetime apex‐VO2peak occurred at 19 weeks of age, and decreased until reaching a steady at 27 weeks of age. There was no difference in mass between 19‐weeks and 27‐weeks in tricep, gastrocnemius, and soleus muscles, discounting the previous associations between declining muscle mass and VO2peak. Currently, we are deciding which of these muscles to use for subsequent analysis. To this end, PGC1α mRNA was compared in all three muscles between 19 and 27‐weeks to aid in selecting a muscle for RNA‐sequencing and protein analysis. PGC1α mRNA was not different in any muscle between 19 and 27‐weeks of age. PGC1α in the tricep showed the WG had 150% higher expression at both 19 and 27 weeks of age compared to the NWG. Also, mitochondrial quantity is being assessed through protein analysis of COX‐IV and cytochrome c. This will aid in our decision for selection of one skeletal muscle to perform RNA‐sequencing on.
The Carotid Baroreflex Modulates the Inflammatory Response to Escherichia Coli Lipopolysaccharide (LPS) ‐ Induced Endotoxemia
Authors: Favaro Laura , Domingos Gean , Santos‐Almeida Fernanda , Castania Jaci , Fazan Rubens , Salgado Helio
Published: June 2021

Our aim was to examine the modulatory effect of electrical activation (EA) of the carotid baroreflex upon the inflammatory responses elicited by LPS. Wistar rats were divided into 3 groups: 1) Control (Saline); 2) LPS; 3) LPS + EA. The subjects were implanted with electrodes around the carotid sinus and catheters into the femoral artery and jugular vein. The surgical procedures were performed under ketamine/xylazine anesthesia. On the next day, the arterial pressure (AP) and heart rate (HR) were recorded, in conscious rats, followed by saline or LPS (1.5 mg/kg iv) administration combined with EA (1mA; 1ms; 30Hz) of the carotid sinus for 1h. Plasma was collected 1, 2 and 3 hs after saline or LPS administration, while the spleen and the heart were collected after 3 hours, to quantify interleukin 6 (IL‐6), 10 (IL‐10), 1β (IL‐1β) and tumor necrosis factor (TNFα). EA did not change the AP or HR, but reduced (LPS vs LPS+EA) inflammatory cytokine TNF‐α (283±139 vs 115±72 pg/µL at the1st h), IL‐6 (11310±1521 vs 3397±709 pg/µL at the 3rd hour) and IL‐1β (296±24 vs 107±29 pg/µL at the1st h), while increased anti‐inflammatory cytokine IL‐10 (25±9 vs 83±25 pg/µL at the 3rd hour). EA reduced IL‐1β (1.66±0.44 vs 1.24±0.14 pg/µg of protein) and increased IL‐10 (0.89±0.08 vs 1.12±0.05 pg/µg of protein) in the spleen, while reduced the IL‐6 (6.43±1 vs 2.88±0.42 pg/µg of protein) and increased IL‐10 (0.8±0.1 vs 1.05±0.14 pg/µg of protein) in the heart. We concluded that electrical activation of the carotid baroreflex, in conscious rats, reduced pro‐inflammatory and increased anti‐inflammatory cytokines, modulating the inflammatory response elicited by LPS.

Financial Support: FAPESP, CAPES and CNPq.
Mechanisms of Folding upon Binding
Authors: Clarke Jane
Published: June 2021

Investigating families of intrinsically disordered proteins that fold upon binding.
One particularly useful approach for investigating protein folding is 'to investigate the folding of several topologically, structurally and/or evolutionarily related proteins in order to discern patterns and trends in folding (stability, pathways and mechanisms). We are now applying this approach to the folding of intrinsically disordered proteins.
The systems we are studying all involve formation of helical structure when a disordered protein binds its target. The properties of these systems are vastly different, binding affinity ranges from µM – nM and association and disassociation rate constants vary by many orders of magnitude. This brings different challenges for determining the kinetics of assembly and disassembly.
We are investigating some fundamental questions in the IDP field: How important is residual structure in the IDP‾ How do regions outside the binding site influence binding‾ What are the mechanisms of binding‾ What role does the partner protein play in determining the binding mechanism and the strength of binding‾ Can we relate biophysical properties to specific IDP functions‾
I will discuss our latest findings.
The Role of Protein Disorder And Self‐Association in the Formation of Cellular Bodies
Authors: Mittag Tanja , Marzahn Melissa , Lee Jihun , Palud Amandine , Marada Suresh , Nourse Amanda , Taylor J , Ogden Stacey
Published: June 2021

Cellular “bodies”, i.e. organelles that are not enclosed by membranes, are large protein assemblies with liquid‐like properties, but the biophysical basis for their formation is largely unclear. Recent work demonstrated that weak, multivalent protein interactions, resulting in the formation of large higher‐order complexes, can undergo phase separation in vitro and may enable the formation of cellular bodies. The inherent size heterogeneity of higher‐order complexes renders them difficult to characterize biophysically, limiting molecular insight into their biological functions. We report novel mechanisms governing the formation of nuclear SPOP bodies and stress granules in which the self‐association of folded domains into large homo‐oligomers and of long disordered regions play key roles. We have used biophysical, biochemical and cell biological approaches to characterize protein self‐association in vitro, to quantify the size distribution of the resulting higher‐order oligomers, and to relate these to the function of organelles in cells. We explore how the destabilization or rigidification of cellular bodies can lead to cancer and neurodegenerative diseases. We propose that dynamic protein self‐association is a general mechanism underlying the formation of cellular bodies. These may serve as signaling hotspots that can be dynamically turned on or off through their regulated assembly and disassembly.
Food Safety and School Garden Program for Elementary and Middle School Students
Authors: Calberry Valerie , Pivarnik Lori , Lofgren Ingrid
Published: June 2021

School food safety education programs have increased knowledge and promoted proper food safety practices, attitudes and beliefs of students. It is important to target children to have them be aware of good food safety practices at an early age. The purpose of the Food Safety and School Garden Program is to improve knowledge and best practices of elementary and middle school students related to the food safety of produce grown in school gardens. This is part of the Farm to School Project which is overseen by Farm Fresh RI, a not‐for‐profit organization with a mission to grow a local food system. The intervention was 2 lessons with interactive activities related to good versus bad bacteria, proper hand hygiene, and harvesting and washing garden produce. Students (N=115), ages 5‐11 years, were evaluated using baseline and post‐intervention tests consisting of 10 knowledge‐based questions. Paired t‐tests showed an increase in knowledge scores, over 39%, in correct responses from baseline to post‐intervention. Number of correct answers significantly increased from 5.3±1.8 to 7.4±2.0 (p<.001). The 2 questions that had the greatest improvement were related to distinguishing good versus bad bacteria and proper produce handling practices. This study supports the importance of early education intervention on proper food safety handling of produce from gardens.
Does Mere Exposure Mediate Sensitivity to Bitter Taste on Consumer Liking and Acceptability of Whole Grain Foods?
Authors: De Leon Angela , Giovanni Maria , Horn William , Burnett Dustin , Keim Nancy
Published: June 2021

Health benefits of whole grains (WG) are well known, yet consumption by Americans falls far short of recommended amounts. A key barrier to WG consumption may be related to taste. Roughly 75% of Americans are sensitive to bitter taste, and WG are known to contain bitter tasting phenolic compounds. It has been reported that individuals with the highest sensitivity, supertasters, prefer refined grain (RG) bread over WG. Other research has shown that with repeated exposure, initially less liked foods ultimately achieve higher acceptance. We aimed to determine the combined effects of bitter taste sensitivity and exposure to WG in individuals who were self‐identified low WG consumers. Healthy adults were provided market baskets of WG or equivalent RG products for daily use over 6 wk. Sensory evaluation (SE) of WG and RG products was conducted pre‐ and post‐intervention using standard taste panel procedures. Scores for overall liking increased (p<0.02) in non‐tasters and supertasters from baseline to 6wk, independent of group assignment or grain type of SE food. These shifts were greater in supertasters, who gave lower overall liking scores (p<0.005) than persons in other taster categories. Supertasters in the WG group were significantly more willing to include SE foods in the diet at 6 wk than supertasters in the RG group (p<0.012). This suggests that while bitter taste sensitivity may influence consumption of WG, with repeated exposure, liking and acceptability can increase.
Mango Supplementation Averts Hepatic and Cardiac Mitochondrial Dysfunction in Mice Fed a High‐Fat Diet
Authors: Ojo Babajide , Wu Lei , Gou Xin , Semkoff Jessica , Janthachotikun Sawanya , Eldoumi Heba , Peterson Sandra , Perkins‐Veazie Penelope , Lin Daniel , Smith Brenda , Lucas Edralin
Published: June 2021

Obesity and its co‐morbidities have been associated with mitochondrial oxidative stress leading to impaired substrate oxidation. This study aimed at investigating the potential ameliorating effects of freeze‐dried mango pulp supplementation on body composition and mitochondrial oxidative capacity in the liver and heart of mice fed a high fat‐diet. Six‐week old male C57BL/6 mice were randomly assigned to 1 of 3 dietary treatment groups: control, high fat (HF=60% fat) and HF + 10% mango (w/w) for 12 weeks. Mango had a modest effect in preventing the increase in body weight and changes in body composition due to HF feeding. HF diet reduced basal oxygen consumption rate (OCR) in the heart (P = 0.01), but not in the liver. Upon stimulation with ADP, an important substrate for the proton gradient coupling with oxidative phosphorylation, hepatic mitochondrial OCR in the control and mango group was significantly increased in contrast to the HF group. Maximal respiratory capacity (MRC) in the liver, as determined by stimulation with the uncoupling agent FCCP, resulted in a significant decrease in MRC in the HF group compared to the control and mango groups. Mango supplementation tended to prevent the reduction in both hepatic and cardiac mitochondrial OCR in response to an antimycin challenge, a complex III inhibitor, in contrast to the HF group. Our findings demonstrated that mango supplementation is beneficial in preventing high‐fat diet‐induced damage at the cellular level by preserving mitochondrial oxidative capacity.
Ripened Cheddar Cheese Peptides Protect Human Vein Endothelial Cells (HUVEC) Against Expression Of Risk Markers For CVD: Role Of Paroaxonase‐2 (PON‐2) As Peptide Molecular Target
Authors: Ravisankar Shreeya , Noratto Giuliana
Published: June 2021

Cardiovascular diseases (CVD) are a major cause of death around the world and dietary bioactive compounds can protect against the risk of CVD. Our objective was to investigate the effects of ripening length on activity of peptides in protecting HUVEC against inflammatory conditions related to CVD.

Peptides extracted from 0,6 and 12 months (mo) ripened cheese were assessed for antioxidant activity by scavenging 2,2′‐azinobis (3 ethyl benzothiazoline)‐6‐sulphonic acid assay. Molecular markers relevant to CVD were investigated in HUVEC treated with peptides (100 μg/mL) using standard molecular biology techniques.

Results show that 6 and 12 mo peptides increased antioxidant activity to 4.1‐ and 3.6‐fold of 0 mo. This might have contributed to decrease in production of reactive oxygen species and H2O2 levels in HUVEC challenged with Escherichia coli lipopolysaccharides (LPS) down to levels of controls not challenged with LPS. The 6 and 12 mo peptides upregulated PON‐2 mRNA (1.2‐ and 1.6‐fold of LPS control) and protein levels. This was accompanied by upregulation of glutathione‐S‐transferase (GST) mRNA (to 2.4‐ and 4.4‐fold of LPS control) and activity (to 1.5‐ and 1.2‐fold of LPS control). The role of PON‐2 as molecular target of cheese peptides was confirmed by siRNA interference. The 6 and 12 mo peptides upregulated PON‐2 protein expression and GST activity in PON‐2 knock down cells at similar extent, while downregulating NF‐κB pro‐inflammatory transcription factor. Overall, these results strongly suggests that cheese peptides modulate PON‐2, an important antiatherogenic and antioxidant molecular target relevant to CVD, though increasing ripening period beyond 6 mo does not alter this effect.
Polyherbal Supplements can Modify Energetics and Lipid Metabolism in Cancer Cells by Activating AMPK Signaling
Authors: Whelan Jay , Zhao Yi , Donohoe Dallas
Published: June 2021

Extensive body of literature demonstrates that a selective blend of herbal extracts inhibit tumor growth at human doses. These tumor suppressive effects are due to multiple mechanisms that arise via synergistic interactions of their components (Huang et al Nutr Ca 2011&2012 and BMC Complement Alternat Med 2014; Zhao et al Func Foods Health Dis 2014). The objective was to determine if the suppressive effects of the polyherbal blend (PHB) involve inhibition of lipogenesis. Cancer cells upregulate lipogenesis via fatty acid synthase (FAS) and acetyl CoA carboxylase (ACC) to generate membrane lipids for rapidly dividing cells. When CWR22Rv1 and PC3 prostate cancer cells were treated with this PHB consisting of 10 well‐defined herbal extracts (see ref above), transcription of FAS and SREBP1c (regulator of FAS) were down regulated and ACC activity was inhibited. AMPK, energy sensor of the cell that regulates multiple steps in lipogenesis, was up regulated by the PHB. RNAi knockdown, pharmacological inhibition/activation, or overexpression of AMPK demonstrated that inhibition of lipogenesis was mediated by the PHB through the activation of AMPK. Inhibition of mTOR signaling (downstream of AMPK) via phosphorylation of raptor and S6K1and down regulation of GβL confirmed involvement of AMPK activation by the PHB. Cellular accumulation of acetyl CoA occurred as a result of inhibition of the lipogenic pathway. The PHB enhanced fatty acid oxidation, an effect likely due to a reduction in malonyl CoA whose levels are regulated by ACC activity. These results suggest that combinations of herbal extracts increase AMPK activation and, in turn, decrease lipogenesis at multiple regulatory sites, in addition to down regulating mTOR signaling and up regulating fatty acid oxidation. (Supported by the TN AES)
Factors Associated with Misreporting of Energy Intake in Food Records: A Validation Study with DLW in Brazilian Low Income Adults
Authors: Lopes Tais , Hoffman Daniel , Ferrioli Eduardo , Luiz Ronir , Sichieri Rosely , Pereira Rosangela
Published: June 2021

Objective

To assess the magnitude of underreport of energy intake (EI) obtained with food records (FR) in low–income adults, and characteristics associated.

Methods

The studied group included 84 adults (20 ‐ 60 years old). Energy expenditure (EE) was estimated using the Doubly labelled water (DLW) method. To define misreporting, the 95% limits of agreement were used. Student T‐test was applied to evaluate differences in the magnitude of misreporting according to exploratory variables (p<0.05).

Results

The limits indicating under and over report were 0.62 and 1.32 for the ratio EI/EE. Underreport of EI was observed in 29% of the participants. In average, UR energy was about 30%. Men presented smaller magnitude of underreported (UR) EI than women. The proportion of UR was higher among less educated participants compared to those who had at least 8 years of education (‐37% vs. ‐25%; p=0.02). Individuals with irregular meals profile showed greater magnitude of UR when compared to those that reported having regularly the main meals (‐46% vs. ‐28%; p=0.03). There was a greater chance of EI underreporting among individuals that regularly replaced lunch or dinner by a snack (OR: 4.5; CI95%: 1.3; 16.1).
Sleep and ultra‐processed intake in early childhood: a longitudinal analyses
Authors: Rauber Fernanda , Vitolo Marcia , Taveras Elsie
Published: June 2021

Objective

To assess whether shorter sleep at preschool age predicted the higher intake of energy and ultra‐processed food in childhood.

Methods

Cohort study conducted with 345 Brazilian children of low socioeconomic status aged 3‐4 years and 7‐8 years. Dietary data were collected through two 24‐hour recalls and children's ultra‐processed foods intake was assessed. Mothers reported the number of hours that the children had slept the past 24h.

Results

Total energy intake at preschool and school‐age was significantly higher in shorter‐sleeping children, with children who slept <10h/d consuming an average of 117 kcal/d (95% CI: 50–184) more than those sleeping for >10 h/d at 3‐4 years; and an average difference of 62 kcal/d (7–117) at 7‐8 year. Regarding changes in diet from pre‐school to school‐age, total energy increased by 54 kcal/d (19–91) and 19 kcal/d (‐66–104) in children who slept 蠅10 and <10 h/d at preschool age, respectively. Intake of energy from ultra‐processed foods increased only in those children who slept <10 h/d. Energy provided by ultra‐processed foods remained constant in children who slept 蠅10 h/d.

Dietary variables
Sleep duration at 3‐4 years

≥10 hours/day
<10 hours/day

mean±SD

At 3‐4 years

Total energy intake (kcal)
1492±253
1610±372*

% energy from ultra‐processed foodsa
45.1±6.1
31.4±4.9*

At 7‐8 years

Total energy intake (kcal)
1548±195
1611±513

% energy from ultra‐processed foodsa
47.7±9.2
48.5±8.8

mean difference (95% CI)

Difference between 7‐8 years and 3‐4 years

% energy from ultra‐processed foodsa
2.4 (0.9—3.9)
17.0 (14.6—19.4)**

* p<0.05, Paired t test. ** p<0.01, Wilcoxon test. a Sweets, savory and biscuits, soft drink, processed meat, and bread.

Conclusion

Early shorter sleep duration was associated with higher energy intake and increased consumption of ultra‐processed foods in children. These findings add new evidence to the limited literature available with children on the role that shorter sleep duration may play in relation to intake.

CNPq, CAPES/Brazil.
Western Diet Affects Autonomic Nervous System Activity in Subordinate but not Dominant Monkeys
Authors: Thayer Julian , Koenig Julian , Shively Carol
Published: June 2021

Research has shown that both lower social status and a Western diet rich in fat and cholesterol are associated with increased risk for cardiovascular disease. However, little is known about how social status and diet interact to effect autonomic nervous system activity. To further explore this association, heart rate (HR) recordings were obtained in a sample of 42 monkeys by telemetry at three different time points: after consumption of a prudent diet (monkey chow) for 6 months (Phase 0, baseline), after consuming a Western diet for 18 (Phase 1), and 34 months (Phase 2). Average recording length and data available for analysis differed by phase (Phase 0: 26.64±4.12h; Phase 1: 27.01±5.93h; Phase 2: 24.19±0.41h). Interbeat intervals (IBI in ms) were recorded and analyzed using MATLAB and Kubios HRV 2.2. After artifact correction the root mean square of the successive differences (RMSSD) was derived as an index of cardiac vagal activity. Social status was assessed based on outcome of aggressive interactions and monkeys were stratified into two groups (dominant vs. subordinate). The groups did not differ while on the prudent diet (HR: p = 0.34, RMSSD: p = 0.57). Social status differences emerged with time consuming the Western diet (HR: 18 months p = 0.13, 34 months p = 0.002; RMSSD:18 months p = 0.42, 34 months p = 0.045). Subordinates monkeys hadsignificantly higherer HR and lower RMSSD after 34 months of Western diet. The data suggest that Western diet may deleteriously affect the autonomic nervous system in subordinate but not dominant monkeys. Thus the cumulative effects of lower social status and poor diet may increase the risk for cardiovascular disease via autonomic imbalance.
Signaling Through the Aryl Hydrocarbon Receptor Induces Expression of the IL‐10 Receptor on Intestinal Epithelia
Authors: Lanis Jordi , Colgan Sean , Kominsky Douglas
Published: June 2021

IL‐10 is an anti‐inflammatory cytokine that inhibits the production of numerous pro‐inflammatory mediators in a number of cell types. Studies in animal models and in humans have demonstrated a role of IL‐10 signaling in a broad range of chronic inflammatory conditions, including inflammatory bowel disease. Signaling by IL‐10 occurs through the IL‐10 receptor (IL‐10R), which is expressed in many cell types, including intestinal epithelial cells (IEC), where it is associated with enhanced mucosal barrier function. Our recent studies revealed that colonic IEC express the IL‐10R in response to IFN‐γ through poorly understood mechanisms. IFN‐γ has also been shown to induce IDO1, an enzyme that catalyzes the degradation of tryptophan to kynurenine. In turn, kynurenine is an endogenous ligand for the aryl hydrocarbon receptor (AHR), a member of the Per‐ARNT‐Sim family of transcription factors. Based on these findings, we hypothesized that the up‐regulation of IL‐10R expression in IEC, and anti‐inflammatory effects that protect against barrier disruption, is regulated by AHR. The promoter region of IL‐10R was found to contain an aryl hydrocarbon response element (AHRE), and luciferase‐based IL‐10R promoter assays showed an increase in gene expression in response to the AHR agonist FICZ. Additionally, western blot analysis confirmed that IL‐10R protein levels were increased in response to FICZ in IEC in vitro. Importantly, studies using both in vitro and in vivo models revealed the abrogation of this response in IEC lacking the transcriptional binding partner of AHR, ARNT. Together, these results provide compelling evidence on the importance of IL‐10 signaling in IEC and implicate the AHR pathway in regulation of IL‐10R expression.
PGC1a rescue retinal pigment epithelial cells from oxidative damage: implication for age‐related macular degeneration
Authors: Khadka Arogya , Iacovelli Jared , Saint‐Geniez Magali
Published: June 2021

Age‐related macular degeneration (AMD) is the leading cause of blindness in the elderly population of industrialized countries. AMD is thought to occur, at least in part, from oxidative damage to the retinal pigment epithelium (RPE). Thus, enhancement of the anti‐oxidant response of RPE is an attractive treatment for AMD. The transcriptional co‐activator, peroxisome proliferator‐activated receptor‐gamma coactivator 1α (PGC‐1α), is powerful mediator of cellular oxidative metabolism, and anti‐oxidant response. Our previous studies showed that PGC‐1α controls RPE oxidative metabolism and maturation. Here we examine the ability of PGC‐1α to protect RPE from oxidative damage. Overexpression of PGC‐1a in RPE strongly induced genes of antioxidant enzymes including CAT, GPX1, PRDX3, SOD1, SOD2, and TXN2. The cytotoxic effect of clinically relevant oxidants including H2O2 (released during photoreceptor outer segment phagocytosis) and hydroquinone (cigarette smoke oxidant) was evaluated. Our results demonstrate that both H2O2 andhydroquinone lead to generation of reactive oxidant species (ROS) and necrosis in RPE in a time‐ and dose‐dependent manner. Importantly, this oxidant‐mediated cytotoxic effect was dramatically reduced by PGC‐1α overexpression. These results demonstrates that PGC‐1α not only controls RPE metabolism but also protect RPE cells from oxidative damage via the induction of a large panel of anti‐oxidant enzymes. Strategies aimed at increasing PGC‐1α expression and/or function may be beneficial for the treatment of retinal degenerative disorders such as AMD.
Sumoylation regulates Cytochrome P450 2E1 (CYP2E1) expression in alcoholic liver disease
Authors: Tomasi Maria Lauda , Ryoo Minjung , Gao Bin
Published: June 2021

Background

Ethanol‐inducible CYP2E1 contributes to increased oxidative stress and steatosis in alcoholic liver disease (ALD). Ubiquitin‐conjugation enzyme 9 (Ubc9), the sole E2‐conjugating enzyme for sumoylation, is induced in the livers of ethanol‐fed mice. Our aim was to examine whether the dysregulated sumoylation could regulate the ethanol‐induced CYP2E1 expression in ALD and elucidate the molecular mechanism(s).

Methods

Studies were done using in vivo binge ethanol‐fed mice and primary mouse hepatocytes. Gene and protein expression were measured by real‐time PCR and Western blot analyses, respectively. Promoter activity, Chromatin Immunoprecipitation (Chip) assay and in vitro protein sumoylation were analyzed using commercial kits.

Results

We found Ubc9 mRNA level is increased in the livers of binge mice and ethanol‐treated hepatocytes whereas CYP2E1 mRNA level increased minimally. In contrast, protein levels of Ubc9 and CYP2E1 are both induced. Ubc9 knockdown reduced CYP2E1 mRNA level and CYP2E1 promoter activity. Chip assay showed that Ubc9 is required for NF‐kB and C/EBPβ, two positive regulators of CYP2E1 promoter activity known to be sumoylated, to interact with CYP2E1 promoter in hepatocytes. Silencing of Ubc9 prevented ethanol‐mediated induction in CYP2E1 protein level when de novo mRNA synthesis is blocked by actinomycin D. Finally, we found that CYP2E1 is sumoylated in vitro and in vivo in binge mice livers and increased following ethanol treatment.

Conclusions

Ethanol‐mediated sumoylation increased CYP2E1 expression in livers of binge mice and primary hepatocytes regulating CYP2E1 promoter activity but the primary role of sumoylation is to stabilize CYP2E1 protein after ethanol treatment.
Depressive Symptoms in Rats with Myocardial Infarction Associated with Local Brain Expression of Neutrophil Gelatinase‐Associated Lipocalin (NGAL)
Authors: Schoemaker Regien , Gouweleeuw Leonie , Liu Hui , Eisel Ulrich
Published: June 2021

Depression is a common co‐morbidity in heart failure, that adversely affects prognosis. However, depression is highly variable, as it is diagnosed as minimally 5 out of 9 symptoms. NGAL is associated with overall depression in heart failure patients. In this study we investigate the association of NGAL with different depressive symptoms in myocardial infarcted rats.
Male Wistar rats were subjected to coronary artery ligation (MI) or sham surgery. After 3‐5 weeks, different depressive symptoms were evaluated using behavioral tests. Plasma, CSF and hypothalamic levels of NGAL were measured (Elisa), and NGAL expression in the paraventricular nucleus of the hypothalamus (PVN) was obtained (immunohistochemistry).
Plasma NGAL levels were increased related to infarct size (r=0.78, p=0.013, N=9), and correlated to CSF and hypothalamic levels, but not to depressive symptoms. NGAL expression in the PVN was increased in MI rats (45±7 vs 26±3 NGAL+ cells per high power field), irrespective of plasma NGAL levels. The number of NGAL positive cells in the PVN was correlated to exploratory behavior in the open field (r=‐0.77, p=0.006); latency to leave the home cage (r=0.51, p=0.026); and sucrose preference (r=0.60, p=0.009), but not to anxiety in the elevated plus maze.
Data indicate that while circulating NGAL, representing severity of heart failure, is reflected in CSF and may hence enter the brain, depressive symptoms after myocardial infarction in rats rather are associated with local expression of NGAL in the brain.
Implementing a Cooperative Learning Model in a Cadaver Anatomy Laboratory
Authors: Saltarelli William , Lee You‐kyung , Roseth Cary
Published: June 2021

For instructors of human anatomy, it remains unclear whether some teaching methods are more likely to enhance student motivation and achievement than others. This presentation focuses on Jigsaw, a cooperative learning technique. In Jigsaw, students divide into groups to learn subsets of objectives. After mastering their subset, students then form new groups in which each student teaches their subset to students who, in turn, teach their subsets. The purpose of this work is to explain how the Jigsaw procedure was modified for use in the anatomy laboratory and to provide data comparing Jigsaw with traditional lab instruction in which students work on their own.

The Jigsaw method was modified to teach 300 students in a one‐semester cadaver based laboratory. Fifteen laboratory sections were randomly assigned to either traditional lab instruction or Jigsaw. Surveys were given across the semester to assess student motivation and engagement. Achievement was assessed at the end of each laboratory session (exit quizzes) and on six unit exams.

Jigsaw students scored significantly higher on all exit quizzes. However, no significant differences were detected on the systems exams. Jigsaw students' motivation also increased compared to the traditional lab, as measured by interest, engagement, and positive emotions.

Jigsaw was implemented in an undergraduate cadaver anatomy course. Not only were students were more successful in learning anatomical structures using Jigsaw, but their motivation increased as well. Further research should focus on the long‐term retention of material in a cooperative learning environment.
Tablets in the Gross Anatomy and Neuroanatomy Labs: Quick and Dirty Can Work
Authors: Druzinsky Robert , Doubleday Alison
Published: June 2021

In the past five years there have been major changes in the education of students in the College of Dentistry. These changes include an emphasis on student‐centered, small group learning (Crawford et. al., 2007), smaller cohort sizes; use of iPads in the gross anatomy lab (Doubleday, 2014); and distribution of iPad Minis to all students. In past years, students in the neuroanatomy lab were given a lab manual and access to textbooks and atlases. This year faculty began to utilize software to create online learning modules for didactic, as well as gross anatomy and neuroanatomy lab sessions. The lab manual was supplemented with a self‐guided tutorial (SoftChalk©) in the Blackboard© course site. For each gross anatomy lab session and for select didactic sessions, students were also provided with a self‐guided tutorial (SoftChalk©) to complete prior to class.

In response to student requests for self‐guided instruction materials for the neuroanatomy lab, brains were photographed using a cellphone, and images were labeled and made available to students for use during subsequent labs and for study outside of class. Although faculty anticipated that image and video quality achievable on mobile devices would not be good enough to encourage adequate learning, various measures indicate that student outcomes are improving. Scores for the neuroanatomy portion of the basic sciences course in 2014 were significantly higher than in 2013. Scores on anatomy lab practical exams have risen steadily over the past three years, and students have achieved a 100 percent pass rate on the National Board Part I for the past three years. This presentation outlines strategies, challenges, and benefits of including mobile‐accessible learning materials that are “quick and dirty” but good enough.
Connecting heart and head muscle development in a DiGeorge syndrome mouse model
Authors: Kelly Robert
Published: June 2021

Cardiac and craniofacial congenital defects are among the most prevalent congenital anomalies. New data has revealed a link between heart and head muscle development in the early embryo. Cardiopharyngeal mesoderm associated with the developing foregut or pharynx contains common heart and head muscle progenitor cells and perturbation of this developmental field results in a spectrum of cardiac and craniofacial congenital anomalies, typified by DiGeorge or 22q11.2 deletion syndrome. These include the most common forms of congenital heart defects, reflecting the critical role of addition of second heart field progenitor cells to growth of the embryonic heart. The transcription factor TBX1 is the major gene implicated in DiGeorge syndrome and regulates both cardiac and skeletal myogenic derivatives of pharyngeal mesoderm. Here the epithelial properties of pharyngeal mesoderm will be discussed, as well as Tbx1 function in segregating cardiac progenitor cells to the arterial and venous poles of the heart from a common progenitor pool in posterior pharyngeal mesoderm that additionally contributes to skeletal muscles.
Cell‐type specific hippocampal circuit mapping by genetically modified rabies virus
Authors: Xu Xiangmin
Published: June 2021

The mammalian hippocampus plays a key role in spatial memory and navigation. The general anatomy and circuit organization of hippocampus has been well studied; however, there is a limited understanding of whether or how the different sources of inputs are distributed in different strengths onto each of its constituent cell types. New viral approaches are now beginning to complement more traditional approaches and offer powerful tools for mapping cell‐type specific circuit connectivity and function. Here we have applied a new Cre‐dependent, genetically modified rabies‐based tracing system to map local and long‐range monosynaptic connections to targeted cell types defined by Cre expression in CA1 of the mouse hippocampus. We found common inputs to excitatory and inhibitory CA1 neurons from CA3, CA2, entorhinal cortex and the medial septum (MS), and unexpectedly also from the subiculum. Excitatory CA1 neurons receive inputs from both cholinergic and GABAergic MS neurons while inhibitory CA1 neurons receive a great majority of input from GABAergic MS neurons; both cell types also receive weaker input from glutamatergic MS neurons. Comparisons of inputs to CA1 parvalbumin‐expressing (PV+) interneurons versus somatostatin‐expressing (SOM+) interneurons show similar strengths of input from the subiculum, but PV+ interneurons receive much stronger input than SOM+ neurons from CA3, entorhinal cortex and MS. Differential input from CA3 to specific CA1 cell types was also demonstrated functionally using laser scanning photostimulation and whole cell recordings. Together these data provide new insights into differential circuit mechanisms underlying functionally distinct memory circuits and inhibitory neuronal control of hippocampal target neurons.