bluuebunny/crossref_metadata_2025 huggingface dataset:
Knowledge and perceptions on high blood pressure risk, healthy lifestyles, and use of mobile phone in 3 Latin American countries
Authors: Ramirez-Zea Manuel , Estrada Karin , Letona Paola , Beratarrechea Andrea , Diez-Canseco Francisco , Miranda Jaime J , Rubinstein Adolfo , Salguero Julissa , Martinez Homero
Published: June 2021

Background

Preventive interventions for high blood pressure (HBP) are urgently needed in developing countries.

Objective

Formative research to assess perceptions and knowledge on HBP risk, healthy lifestyle and use of mobile phone for health advice among adults living in urban areas in Argentina, Peru and Guatemala.

Methods

Focus group discussion segmented by gender (4/country, 5–13 subjects each) with healthy men and women, 30–59 yrs old. Qualitative analysis was done by topic (HBP, healthy lifestyles, use of mobile phone), country and sex.

Results

Women related HBP to salt intake, menopause, pregnancy and breastfeeding; men related HBP to salt intake, being over 50 yrs and to a cause of death. Barriers identified to follow a healthy diet were: income, knowledge, overeating and time. Men also mentioned eating away from home as a barrier. Women saw physical activity as a group event and men as a structured activity (e.g. gym workouts). All subjects perceived their mobile phone as a daily necessity. Men tended to be more possessive with their mobile phone, while women more often shared it with other family members. No relevant differences were found among countries.

Conclusions

Gender differences in perceived HBP risk, food preparation, eating habits and physical activity choices should be specifically addressed. Mobile phones seem to be a useful tool to deliver health advice.

Funding: NHLBI HHSN 268200900028C
Role of β‐hydroxy‐β‐methylbutyrate (HMB) in leucine stimulation of muscle mitochondrial biogenesis
Authors: Stancliffe Renee A , Zemel Michael B
Published: June 2021

We have previously demonstrated leucine to increase Sirt1 activity, mitochondrial biogenesis and fatty acid oxidation in muscle cells. While the mechanism of these effects is not clear, it is likely that the leucine metabolites α‐ketoisocaproic acid (KIC) and HMB play a role. Dietary leucine is transaminated by branched‐chain aminotransferase (BCAT) to the α‐keto analogue (KIC), which is then metabolized into isovaleryl‐CoA or HMB by KIC‐dioxygenase. Approximately 5 to 10% of ingested leucine is converted into HMB. We have previously demonstrated that KIC and HMB both stimulate mitochondrial biogenesis and fatty acid oxidation similarly to leucine. To confirm that these effects of leucine are mediated by its metabolites, we knocked down KIC‐dioxygenase via siRNA transfection in C2C12 myoblasts and then determined the effect of intact leucine (0.5mM) versus HMB (50μM) on myoblast mitochondrial biogenesis (assessed fluorometrically via NAO binding). Both HMB and leucine increased mitochondrial biogenesis by ~30–35% (p<0.05) in the absence of KIC‐dioxygenase knock‐down. However, cells treated with siRNA failed to exhibit stimulation. Thus, leucine and KIC modulation of muscle mitochondrial biogenesis appear to be mediated by the leucine metabolite HMB.
Dietary intake ratio of calcium‐to‐phosphorus and sodium‐to‐potassium are associated with levels of serum lipids in healthy Korean adults
Authors: Bu So Young , Kang Myung-Hwa , Kim Eun-Jin , Choi Mi-Kyeong
Published: June 2021

The purpose of this study was to identify food sources of major minerals such as calcium (Ca), phosphorus (P), sodium (Na) and potassium (K), and to evaluate the relationship between dietary intake of these minerals and serum lipids in healthy Korean adults. A total of 132 healthy men and women completed physical examination, diet records and blood draw for analysis of lipid profiles. Results showed that the daily average mineral intake was 373.4 mg for calcium, 806.0 mg for phosphorous, 3685.8 mg for sodium, and 1938.3 mg for potassium while the calcium‐to‐phosphorus and sodium‐to‐potassium ratio was 0.5 and 2.0, respectively. The major sources for minerals were vegetables (24.9%)/fishes (19.0%) for calcium, grains (31.4%) for phosphorous, seasonings (41.6%)/vegetables (27.0%) for sodium, and vegetables (30.6%)/grains (18.5%) for potassium. The correlation analysis adjusted for age, sex, food consumption, and energy intake showed significantly positive correlation between Ca/P and the level of serum HDL cholesterol, between Na and the level of total serum cholesterol, and between Na/K and the level of serum cholesterol and LDL‐cholesterol. These data indicate that the level of mineral consumption partially contribute to serum lipid status and particularly a diet low in Ca/P ratio and high in Na/K ratio could have a negative impact on lipid metabolism.
Does infant mood affect offered bottle size? An exploratory analysis of secondary objectives of the Baby‐Mine study
Authors: Nicklas Jennifer C , Greer Betty P , Burney Janie L , Kavanagh Katie F
Published: June 2021

A secondary objective of a larger project assessing impact of bottle contents on rate of infant weight gain was to evaluate the relationship between infant mood and offered bottle size. Mothers of healthy, term, formula‐fed infants (< 3 months) were recruited via fliers, social media websites, and a birth registry. Mothers were asked, at two time points, to record infant intake for 48 hours and to indicate infant mood prior to each offered bottle (unhappy, neither, or happy). Mid‐point analysis consisted of 31 mothers with complete data at both time points (TP): TP1 ~2.3 mo of age and TP2 ~4.1 mo of age. The sample was somewhat heavily weighted towards male infants (58.1%). Average birthweight was 3230g, and infants gained an average of 27.4g/d while in the study. Average size of bottles offered increased from TP1 (4.8oz) to TP2 (5.8oz). Mood categorization resulted in 45.2% of infants categorized as “happy” at TP1 and 51.6% as “neither” at TP2. ANOVA, with mood as the categorical variable, detected no relationship between mood and bottle size offered. Additional categorization of bottle size into “small” (≤ 4 oz) and “large” (>4 oz) did not result in significant findings. However, the sample size at the mid‐point evaluation likely precludes the detection of a significant difference, should it exist, and a larger sample size is needed. Data collection is ongoing and more robust results and suggested future work will be presented.

Funds: USDA/NIFA/AFRI Award ‐2010‐85215‐20663.
Development of a home feeding intervention for resource‐limited parents of 3–5 year old children
Authors: Reznar Melissa , Hoerr Sharon , Murashima Megumi
Published: June 2021

Purpose

To describe the development and pilot testing of a dualmedia nutrition intervention for parents of 3–5 year old children enrolled in a federal preschool program.

Methods

A multidisciplinary team developed a self‐guided workbook with complementary DVD clips featuring parents discussing family food experiences. In a pilot test, 42 parents and their preschool children were randomly assigned to an intervention (n=23) or control group (n=19) for 8 weeks, with a 6‐week post‐visit. Participants completed 2 evaluations for program acceptability and success.

Results

Five topics comprised the intervention: 1) home food environment, 2) food modeling, 3) praise, 4) mealtime fun, and 5) difficult mealtime behaviors. Sixteen parents in the intervention (70%) and 19 in the control group (100%) completed the pilot. Intervention parents rated the program favorably, with a majority agreeing or strongly agreeing that the program was beneficial (94%), suggested good ways to handle problems (81%), and was effective in changing mealtimes (94%). Only 56% parents agreed or strongly agreed that they as parents needed such a program.

Conclusions

This parent feeding intervention was well received, but needs testing in a larger, wider audience. Targeting parents with higher perceived need might enhance program effectiveness.

Financial support: NIH NICHHD Grant Number 1R21HD064876‐ 01A1
β‐Cryptoxanthin supplementation inhibits carcinogen‐initiated and nicotine‐promoted lung tumor development in AJ mice
Authors: Iskandar Anita , Liu Chun , Ernst Hansgeorg , Choi Sang-Woon , Ausman Lynne , Wang Xiang-Dong
Published: June 2021

Recent epidemiologic studies show that increased dietary β‐cryptoxanthin (BCX) intake, rather than β‐carotene used in earlier human trials, is associated with reduced risk of lung cancer. However, BCX efficacy on lung carcinogenesis has not been reported. Here, we report the protective effects of different doses of BCX against lung carcinogenesis at the initiation and promotion stages in AJ mouse models. In the tobacco carcinogen NNK‐initiated lung carcinogenesis model, we found a 52–63% reduction of lung tumor multiplicity in mice pre‐treated with BCX at 0.2 and 2 mg kg BW‐1 d‐1, as compared to the NNK group, P<0.01. In the NNK‐initiated and nicotine‐promoted lung cancer model, we found that nicotine not only induced emphysema, a risk for lung cancer, but also increased greatly lung tumor multiplicity of the NNK‐treated mice. Notably, BCX at 2 and 4 mg kg BW‐1 d‐1 prevented nicotine‐induced emphysema and decreased tumor multiplicity by 86–91%, P<0.01. BCX protection was associated with suppressions of lung AKT activation, IL‐6 and early growth response‐1 mRNA. Unlike β‐carotene reported in prior animal studies, BCX induced retinoic acid receptor‐β mRNA. By HPLC analysis, liver BCX, not retinol, increased in the BCX supplemented mice. Our data suggest that BCX is a unique chemopreventive agent for lung cancer prevention, which is likely to be independent of its provitamin A activity.

Grant Funding Source : NIH R01CA104932
Impact of daily feeding of carotenoid‐rich foods on plasma carotenoid and vitamin A concentrations in lactating women with marginal vitamin A status
Authors: Turner Tami , Burri Betty J. , Haskell Marjorie , Jamil Kazi , Jamil Maleka
Published: June 2021

Vitamin A (VA) is necessary for normal growth, development, immune function, and vision. Carotenoids such as β‐carotene (BC) and β‐cryptoxanthin (CX) can be converted to VA and are often the major source of VA in the diets of people from developing countries. Our clinical trial is assessing the impact of a dietary intervention with foods rich in CX and BC on plasma and breast milk concentrations of VA, BC, and CX. We randomly assigned breastfeeding women to receive a VA supplement (0.5 mg), tangerines (6 mg CX), orange sweet potatoes (12 mg BC), or white potatoes (0 mg RE) in divided doses 6 days a week for three weeks. Concentrations of VA, BC, and CX are measured in plasma and breast milk at baseline and at 3 weeks. We report the responses of VA, BC and CX in plasma herein. Baseline concentrations of analytes were not different. Changes in BC and CX were significantly higher in plasma in the respective treatments groups receiving BC (p<0.005) and CX (p<0.001). Changes in plasma VA was higher in the BC group and the VA supplement group; however, as anticipated, after controlling for initial retinol values only the group receiving the VA supplements was statistically different than the control group (p<0.001). As plasma VA is homeostatically controlled, we expect that VA in breast milk will provide a better indicator of changes in VA status from treatment and therefore give information of the bioefficacy of the conversion of BC and CX to VA in humans. Supported by AFRI/NIFA Grant 2008‐01889.
Exploring Shopping Habits and Nutrition Knowledge of Single Mothers in Transitional Housing
Authors: Sweitzer Sara Johnson , Romo Maria , McAllaster Michael , Briley Margaret E
Published: June 2021

Objective

Transitional housing offers an opportunity for nutrition intervention for single mothers with children. As they transition out of homelessness mothers and children are frequently reestablishing lifestyle dietary habits that include budgeting, grocery shopping and food preparation. This study examined the nutrition knowledge and food purchasing habits of single mothers in transitional housing.

Methods

Mothers at a small transitional housing project in central Texas were invited to participate in a nutrition study. Data collection included mother questionnaires for dietary habits and nutrition knowledge, grocery receipts as well as heights and weights.

Results

The mothers (n=21) averaged 36.2 years old with an average BMI of 30.4. Mothers reported frequently drinking milk, 75% (n= 16) and occasionally using the food label when purchasing, 52.3% (n=11). The top five types of foods the mothers purchased were fruit, 11.4% (n=34), sugar sweetened beverages, 11.1% (n=33), Dairy products, 9.7% (n=29), vegetables, 8.7% (n=26), and candy/confections, 6.7% (n=20).

Conclusion

Single mothers that are in a supportive housing environment would benefit from a targeted nutrition intervention that addressed food behaviors, nutrition knowledge and food purchasing guidance.
Relationship between nutritional status and the prevalence of malaria and anemia among children in the Kassena‐Nankana District of Ghana
Authors: Asare Simone Yeboaa , Paintsil Elijah , Koram Kwadwo , Atuguba Frank , Asoala Victor , Humphries Debbie
Published: June 2021

Under nutrition, malaria and anemia are significant public health concerns in Ghana, especially among children under five years. There is growing interest in the effects of nutritional status on clinical malaria outcomes in pre‐school age children.

Objectives

To characterize the effects of indicators of dietary risk on clinical malaria during both the wet and dry seasons.

Methods

Cases of clinical malaria in the previous wet season (n=49) and dry season (n=60), and matched controls (wet season n=72, dry season n=55) were identified from records of the longitudinal Birth Cohort Study. Clinical indicators (Hgb, malaria parasitemia, weight) were extracted from study records, and household questionnaires captured indicators of household hunger, dietary diversity, household food security, and malaria risk behavior.

Results

Significantly more cases of malaria in both the wet and dry seasons came from families who reported household hunger (McNemar p‐values <0.001 for both seasons). In the wet season, 22.5% of cases reported hunger, compared to 16.9% of the controls; in the dry season, cases reported 30% compared to 18.2% of the controls.

Conclusion

Independent of season, hunger is associated with higher rates of clinical malaria among preschool aged children in the KND. Study funded by Wilbur G. Downs International Health Fellowship & Office of Student Research, Yale School of Medicine.
Modifying placement and simplifying menu labels in a foodservice operation reduces the energy content purchased by patrons
Authors: Chu Yong H. , Jones Sonya J. , Frongillo Edward A. , Thrasher James F. , DiPietro Robin B.
Published: June 2021

Restaurant patrons may have inadequate time or nutrition knowledge to use menu labels in a fast‐paced foodservice setting. This study tested two changes to menu labeling in a cafeteria setting. We changed the placement of labels (i.e., floor stand placed where patrons queued v. above the food). We also provided a simple label (i.e., entrée description and kcal) v. the Nutrition Facts Panel. The quasi‐experimental, single‐group, interrupted time‐series design allowed us to test two placements and two types of labels and compare sales data for a total of 20 weeks. We analyzed mean differences in average energy content of entrées sold among the 4 intervention conditions, accounting for secular trend over the 20 weeks. Average energy content of entrées was lowest (by −27.5 kcal) with the condition of simple menu labels placed where patrons were queued. Modification to the placement of menu labels and reducing the amount of nutrition information on menu labels may help patrons reduce average energy content of entrées purchased.

Grant Funding Source : University of South Carolina
Improving Nutrition in the Supplemental Nutrition Assistance Program: A Qualitative Study
Authors: Leung Cindy W , Hoffnagle Elena E , Lindsay Ana C , Turrell Sophia , Willett Walter C , Blumenthal Susan J
Published: June 2021

The Supplemental Nutrition Assistance Program (SNAP) is the largest federal food assistance program. Using in‐depth interviews, this study explored the opinions of leading experts concerning the existing challenges and innovative strategies to improving nutrition among SNAP recipients. Twenty‐seven individuals were interviewed from academic/research organizations, government, advocacy and industry groups. Interviews were recorded, transcribed, coded, and analyzed for thematic content. Economic, political and environmental factors were identified as variables that influence nutrition among low‐income households including: the prohibitive cost of nutrient‐rich foods such as fruits and vegetables, inadequate SNAP benefit amounts and poverty‐related environmental factors. Respondents proposed multi‐level strategies to address these challenges, including providing incentives to purchase nutrient‐rich food; restricting the purchase of energy‐dense foods with minimal nutritional value with SNAP benefits; modifying when SNAP benefits are distributed; enhancing nutrition education; improving the SNAP retailer environment; and increasing state/federal coordination. Given the recent increase in SNAP enrollment, policymakers should consider implementing these strategies so the program continues to address food insecurity and provide a healthful diet for all SNAP beneficiaries.

Grant Funding Source : Robert Wood Johnson Foundation; Aetna Foundation; National Institutes of Health
Cancer Metabolism, HIF‐1, and Novel Anti‐Cancer Therapies
Authors: Semenza Gregg L.
Published: June 2021

Increased glucose uptake and metabolism is a universal characteristic of advanced solid cancers. There are two well‐established mechanisms underlying the reprogramming of tumor metabolism. First, intratumoral hypoxia induces the activity of the transcriptional activator hypoxia‐inducible factor 1 (HIF‐1) by inhibiting the O2‐dependent prolyl and asparaginyl hydroxylases that inhibit HIF‐1α stability and transactivation, respectively. Second, genetic alterations increase the activity of HIF‐1. In either case, HIF‐1 increases the expression of glucose transporters (GLUT1, GLUT3), glycolytic enzymes (ALDOA, ENO1, HK2, LDHA, PKM2), pH regulators (CAR9, NHE1, MCT4), and proteins that inhibit mitochondrial metabolism (BNIP3, PDK1). We have identified a novel feed‐forward mechanism by which PKM2 expression leads to increased HIF‐1 transcriptional activity. This pathway may be designed to increase HIF‐1 activity under non‐hypoxic conditions and may be of importance in cancers where genetic alterations increase HIF‐1α expression in an O2‐independent manner. We have also demonstrated that daily administration of digoxin, acriflavine, or low‐dose doxorubicin blocks tumor growth and inhibits HIF‐1 activity by blocking HIF‐1α synthesis, HIF‐1α:HIF‐1β dimerization, and HIF‐1 DNA binding, respectively.
The role of Ypt/Rab GTPases in Traffic Coordination
Authors: Segev Nava , Lipatova Zhanna , Taussig David , Kim Jane
Published: June 2021

Transport between cellular compartments is mediated by vesicles that bud from one compartment and fuse with the next. Ypt/Rab GTPases and their effectors mediate all the known aspects of vesicular transport, from formation and motility, to targeting and fusion. An attractive idea is that in addition to regulating individual transport steps, Ypt/Rabs also integrate these steps into whole pathways and coordinate them with other cellular processes. In yeast, three Ypts regulate the exocytic pathway: Ypt1 regulates entry to the Golgi, Ypt31/32 control exit from the Golgi, and Sec4 regulates fusion of Golgi vesicles with the plasma membrane (PM). We have uncovered three types of Ypt‐mediated coordination mechanisms. First, we found that Ypt31/32 and Sec4 interact with common proteins to couple Ypt31/32‐mediated vesicle formation and motility with Sec4‐mediated vesicle tethering and fusion. Second, we propose that sequential activation of Ypt1 and Ypt31/32 by the modular complex TRAPP coordinates Golgi entry and exit, thus integrating these two transport steps into a whole pathway. Third, we identified novel effectors of Ypt1 and Ypt31/32 that coordinate the exocytic pathway with other cellular process like autophagy and PM recycling. In summary, we propose Ypt/Rab interactions and sequential activation as mechanisms by which these highly conserved GTPases coordinate trafficking inside cells.
Fatty acid transport protein mediates macrophage polarization
Authors: Qin Yuanyuan , Sampey Brante , Sacks Gina , Freemerman Alex , Li Lei , Coleman Rosalind , Stahl Andreas , Makowski Liza
Published: June 2021

Macrophage (MP) subtypes exist and modulate inflammation in adipose. “M1” MPs are pro‐inflammatory and rely upon glucose metabolism, while anti‐inflammatory “M2” MPs use fatty acid oxidation. The objective of this study is to investigate how fatty acid metabolism modulates MP activation. We stably overexpressed (OE) FATP1 in RAW264.7 MPs. FATP1‐dependent acyl‐coA synthetase (ACS) activity and fatty acid oxidation demonstrated functional FATP1. MPs were treated with 100ng/mL LPS to induce inflammation. qPCR and Westerns detected proinflammatory factors TNFα and MCP‐1, and glucose transporter 1(GLUT1), glucose uptake and glucose metabolism were examined. Bone marrow derived MPs (BMDM) from FATP1+/+ and FATP−/− mice were polarized to M1 and M2 subtypes and pro‐inflammatory factors, GLUT1 expression, glucose uptake and glucose metabolism were examined. Results show FATP1 OE drives ACS activity and fatty acid oxidation, and suppresses MP pro‐inflammatory responses vs. empty vector (EV). FATP1 OE blunts LPS‐induced GLUT1, glucose uptake, and oxidation. FATP1−/− BMDM display enhanced pro‐inflammatory M1 responses compared to FATP1+/+. FATP1−/− exacerbates the M1 phenotype with elevated cytokines, GLUT1 expression, and glucose uptake. In conclusion, FATP‐1 OE blunts the inflammatory response in MPs and drives M2 polarization, while FATP‐1 deficiency drives the M1 phenotype. R00 AA017376

Grant Funding Source : NIH‐NIAAA
Biofortified red mottled beans (Phaseolus vulgaris L) in a maize and bean diet provide more bioavailable iron than standard red mottled beans: Studies in poultry (Gallus gallus) and an in vitro digestion/Caco 2 model
Authors: Tako Elad , Blair Matthew W , Glahn Raymond P
Published: June 2021

Our objective was to compare the capacities of biofortified and standard colored beans to deliver Fe for hemoglobin (Hb) synthesis. Two isolines of red mottled Andean beans (Phaseolus vulgaris L), standard (“Low Fe”, 49μg Fe/g) and biofortified (“High Fe”,71μg Fe/g) in Fe were used. Bean based diets were formulated to meet the nutrient requirements for broiler except for Fe (42±1 and 54±0.9 mg/kg). Chicks (Gallus gallus) were allocated to the experimental diets (n=12). For 4 weeks, Hb, feed consumption and body weights were measured. Hemoglobin maintenance efficiency differed between groups on days 14 and 21 of the experiment (P<0.05). Hb‐Fe contents differed between standard (12±1mg) and high Fe (15±0.6mg) bean groups (P<0.05). Duodenal DMT1, DcytB and ferroportin expressions were higher and liver ferritin was lower in the standard group vs. the biofortified group. In vitro analysis showed lower Fe bioavailability in cells exposed to standard (“Low Fe”) bean diet. We conclude that this 22μg/g increase in bean Fe concentration delivered more absorbable Fe as indicated by our in vitro and in vivo models. This justifies further work on the Andean beans which are the staple of regions where Fe deficiency anemia is a primary cause of infant death and poor health status. Moreover, application of this screening approach should be effective in planning human efficacy trials.
Preliminary characterization of secreted bioactive compounds from Bifidobacterium longum with modulatory activity towards enterocytic Fasting Induced Adipocyte Factor (FIAF)
Authors: Pham Priscilla , Cotten Reese , Kolinek Travis , Parker Shaniece , Vattem Dhiraj , Maitin Vatsala
Published: June 2021

Gut bacteria have been shown to influence diet‐related obesity, mediated in part via intestinal FIAF, a circulating lipoprotein lipase inhibitor that modulates fat‐storage in the adipose tissue. Probiotic bacteria and probiotic‐derived bioactive compounds with stimulatory activity towards intestinal FIAF may thus serve a protective function against diet‐related obesity. We have previously shown that secreted factors from Bifidobacterium longum (B. longum), a resident member of the human gut and a probiotic, significantly increased the levels of FIAF secreted from enterocytes in vitro. The objective of this study was a preliminary characterization of the secreted bioactive compounds from B. longum responsible for the observed increases in enterocytic FIAF levels. Our experiments revealed that the modulatory factors were produced by B. longum primarily during exponential phase and caused a concentration‐dependent increase in FIAF‐secretion. Potent increases in FIAF levels were produced by fractions of molecular weight >50kDa isolated from B. longum cell free supernatants. Heat‐treatment did not impact their ability to increase FIAF levels but freeze‐thaw lead to loss of modulatory activity. Trypsin‐ or pepsin‐treatment of cell free supernatants also led to loss of FIAF‐increasing ability, suggesting that the modulatory factors may be secreted B. longum proteins.

This research was funded in part by the Texas State University Research Enhancement Program.
Wild Blueberry consumption markedly attenuates concentration and expression of inflammatory markers in the obese Zucker rat
Authors: Vendrame Stefano , Daugherty Allison , Kristo Aleksandra S. , Klimis-Zacas Dorothy
Published: June 2021

This study investigates the ability of a wild blueberry (WB)‐enriched diet to improve subclinical inflammatory status in the obese Zucker rat (OZR), an experimental model for the human metabolic syndrome. Twenty OZR and 20 lean controls (LZR) were fed either a control (C) or an 8% WB diet for 8 weeks. Blood levels of interleukin 6 (IL6), TNFα and adiponectin (APN) were significantly higher in OZR compared to LZR, independent of treatment. Within the OZR group, IL6 and TNFα were significantly lower in the WB group (219.3 ± 8.0 and 28.8 ± 0.8 pg/mL respectively) compared to controls (257.7 ± 7.7 and 38.7 ± 0.9 pg/mL), whereas APN levels were higher (20.7 ± 1.5 vs 17.0 ± 1.1 μg/mL). Expression of IL6, TNFα and NF‐kB was significantly lower in the WB group of OZR both in the liver (−65%, −59% and −25% respectively) and the abdominal adipose tissue (−64%, −52% and −65%). Furthermore, expression of these genes was markedly increased in OZR on C diet compared to their lean controls, and this effect was almost completely reversed by the WB treatment. Liver expression of C‐reactive protein significantly decreased in both groups following WB treatment (−16% in LZR and −25% in OZR). Expression of APN in the adipose tissue significantly increased following WB treatment in LZR (+25%), but not in OZR. In conclusion, results of this study suggest that WB consumption results in a markedly improved inflammatory status in the OZR.

Grant Funding Source : Maine Wild Blueberry Commission
Liver Specific Knockout Atg5 Causes Persistent Activation of Nrf2 and Protects Against Acetaminophen‐Induced Liver Injury
Authors: Ding Wen-Xing , Ni Hong-Min , Apte Udayan , Jaeschke Hartmut
Published: June 2021

Autophagy is a biological process which degrades intracellular proteins and organelles including damaged mitochondria through the formation of autophagosome. We previously demonstrated that pharmacological induction of autophagy protected against acetaminophen (APAP)‐induced liver injury. To our surprise, in the present study, we found that mice with the liver‐specific knockout of Atg5, an essential autophagy gene, were not more susceptible but rather more resistant to APAP‐induced liver injury. The lack of autophagy in the Atg5‐knockout mouse livers was confirmed by increased p62 protein levels and the absence of LC3‐lipidation as well as autophagosome formation. We also found that Nrf2, a transcriptional factor regulating drug detoxification and glutathione (GSH) synthesis gene expression, was persistently activated in the Atg5 knockout mouse livers. As a result, there were more unconjugated free hepatic GSH and less protein adducts formation in APAP‐treated Atg5 knockout mouse livers than in wild type mouse. In addition, we found that hepatocyte proliferation was significantly increased in Atg5 knockout mouse livers, which might also attenuate APAP‐induced liver injury by promoting liver regeneration. In conclusion, we found that persistent activation of Nrf2 and increased hepatocytes proliferation protected against APAP‐induced liver injury in Atg5‐liver specific knockout mice.
Gender differences in decreased ambulation and balance associated with Alzheimer's Disease
Authors: OˈMahony Erin , Schlueter Heather , Hong Junggi , Stavrianeas Stasinos
Published: June 2021

This is a preliminary report on the effects of Alzheimer's Disease (AD) on motor function, a less‐studied effect of this debilitating disease. We analyzed gait characteristics using the Gaitrite system (n=10 F, n=7 M) and balance using the BioSway (n=4 F, n=4 M) along with a standard timed Get‐Up‐And‐Go (GG) test (n=10 F, n=9 M). All participants (aged 81.2±6.6 years) were clinically diagnosed with AD. Our results reveal that men performed significantly better than women in the GG (14.71±8.74 s vs. 32.15±18.33 s respectively, p<0.02). There were no gender differences in stride length (left leg vs. right leg p=0.06 and p=0.07 respectively) and single leg support time (left vs. right leg p=0.74 and p=0.55 respectively). Further, there were no gender differences in medial/lateral (p=0.76) or anterior/posterior balance (p=0.96). Our results indicate that men and women exhibit similar declines in ambulatory performance with AD. We are investigating whether gender differences may be attributable to muscle mass, prior levels of activity, and progressive stage of the disease.

This work was supported through Willamette University iHSI and Atkinson grants to JH and SS.
High dose vitamin D is associated with decreased inflammatory markers and increased number of hospital‐free days in adults with cystic fibrosis: a pilot study
Authors: Grossmann Ruth E , Zughaier S M , Lyles R H , Liu S , Sueblinvong V , Schechter M S , Stecenko A A , Ziegler T R , Tangpricha V
Published: June 2021

Cystic fibrosis (CF) lung disease is characterized by airway inflammation and leads to respiratory failure. Vitamin D (VD) insufficiency occurs in up to 90% of CF patients. Since VD is thought to have anti‐inflammatory properties, we evaluated the impact of VD on markers of inflammation in CF adults hospitalized with a pulmonary exacerbation (PEx).

30 CF adults admitted for a PEx were randomized to a single 250,000 IU oral dose of VD3 or placebo. Serum 25‐hydroxyVD (25D), IL‐6 and TNF‐α concentrations were measured on admission, at 1 week and 12 weeks.

A single, high dose of VD resulted in a significant increase in 25D at 1 week and decrease in TNFα at 12 weeks; there was also a trend for decreased IL‐6 at 1 week compared to placebo. The mean changes (table) were accompanied by 32.2 more hospital‐free days (p = 0.04) and 32.5 more IV antibiotic therapy‐free days (p = 0.07) in the VD group compared to placebo.

High dose VD in CF adults is associated with a decrease in markers of inflammation and an increase in hospital‐free days. VD should be evaluated as adjunct therapy for severe CF pulmonary exacerbations.

Grant Funding Source : Cystic Fibrosis Foundation, National Institutes of Health, BTR Group
Docosahexaenoic Acid (DHA) and Amino Acids (AA) are limiting in Pasteurized Donor Milk from a Cross Sectional Sampling in The North American Milk Banks
Authors: Valentine Christina J , Morrow Georgia , Hodge Amanda , Morrow Ardythe L , Rogers Lynette K.
Published: June 2021

Background

DHA and AA are important nutrients for the growing infant and have been previously shown to be limiting in a Midwestern donor bank. With the increased use of donor milk nationally, it is imperative to understand if these low values are consistent across the United States (U.S.).

Objectives

We tested the hypotheses that the DHA and AA would be lower nationally in donor milk for the high risk infant.

Methods

A prospective sampling of milk from 6 milk banks in North America‐ (New England [NE], Ohio, Michigan, Colorado, Ft Worth, Texas, and California) were collected after informed consent and IRB approval. 15‐ 16 milk samples with lactational stage 1–5.5 months were obtained from each milk bank (except NE, n=6). The samples were pooled to minimize variability. DHA was measured by GC; AA were measured by HPLC. Kruskal‐ Wallis with Dunn's Multiple Comparison was used in analysis.

Results

The DHA content did not differ significantly across banks (median value of 29–39 mg/100 ml), but overall, provided an intake lower than the fetal accretion value for the high risk neonate. AA did not differ except for isoleucine and leucine which were significantly higher in NE (p=0.03)

Conclusion

Nationally, donor milk is low in DHA and variable for isoleucine and leucine. Since the primary target for donor human milk is the high risk neonate, this survey should prompt nutrient supplementation strategies.
Molar surface area and mandibular mechanics: complex scaling relationships in primate masticatory systems
Authors: Holmes Megan Anne , Peburn Tara , DeLeon Valerie
Published: June 2021

Primate evolutionary and comparative studies often rely on an understanding of scaling patterns in the primate masticatory complex. Recently, it was proposed that molar root size predicts masticatory loading and molar crown size predicts facial size. We hypothesize that root surface area (RSA) scales isometrically with mandibular strength, and crown surface area (CSA) scales isometrically with facial size. CT scans of Macaca (n=19) and Papio (n=18) were used to calculate M1 RSA, CSA and facial size (geometric mean of 9 linear distances). Mandibular strength (Zx) was calculated posterior to M1. RMA regressions were used to test scaling patterns among these properties.

RSA was significantly correlated with Zx (r=0.76 and 0.69), exhibiting similar slope trajectories (p=0.182) in both species. Macaca scaled with isometry, however Papio was negatively isometric. RSA and facial size scaled isometrically in both taxa with similar slopes and elevations. In contrast, CSA displayed divergent scaling patterns relative to both Zx and facial size. For both variables, Papio possessed a significantly greater CSA slope trajectory. CSA scales isometrically with Zx and facial size in Papio, but with negative isometry in Macaca. Results partially support our hypotheses yet indicate that unique species‐specific scaling relationships exist for CSA and suggest that future studies should control for phylogenetic signals.

Grant Funding Source : NIDCR (R03‐DE019816)
Overexpression of MnSOD and CoQ10 treatment attenuate NRTI‐induced endothelial dysfunction
Authors: Glover Mitzi , Hebert Valeria Y. , Xue Stephen , Zavecz James H. , Dugas Tammy R.
Published: June 2021

Combination drug therapies for HIV have significantly slowed disease progression and mortality, uncovering toxicities associated with chronic treatment. Nucleoside reverse transcriptase inhibitors (NRTI), the backbone of these therapies, have been linked to cardiovascular pathologies, including atherosclerosis. Our studies have shown that mice treated chronically with NRTIs exhibit endothelial dysfunction, an early marker for atherosclerosis. Moreover, our in vitro studies indicate that mitochondrial toxicity via oxidative stress may result in stress‐induced premature senescence (SIPS), a possible mechanism for the development of this dysfunction. In this study, transgenic mice overexpressing the mitochondrial antioxidant MnSOD were protected from NRTI‐induced endothelial dysfunction. Endothelial cells treated with coenzyme Q10, a critical cofactor for mitochondrial electron transport, also demonstrated protection from NRTI‐induced alterations in ROS production, ATP generation, and O2 consumption. Analysis of whether SIPS is a mechanism of NRTI‐mediated dysfunction and whether it can be prevented by antioxidant therapy is ongoing. This work was supported by R01‐ HL082472‐0251.
Developing A Photographic Atlas Of Early Fetal Anatomy
Authors: Hartpence Jesse , Hubbard Chris
Published: June 2021

Numerous atlases are available showing the anatomy of the adult human, however, to our knowledge, only one photographic atlas of late stage fetal anatomy has ever been published (Parke, 1975). Specimens from the embryonic period (day 0 – 7 weeks post conception) have been extensively documented photographically (ex. The Carnegie collection). Fetal descriptions in embryology text books show an occasional photograph but most fetal anatomy is illustrated with drawings leaving the true anatomical picture to the student's imagination. Because fetal material is, by nature, difficult to obtain, anatomy students (medical and otherwise) will likely never see or be able to dissect a real fetal specimen. The purpose of this study is to develop a photographic atlas of early stage fetal anatomy. Dissections were performed on fetuses between 12 and 27 weeks of age. The dissections were photographed using an Olympus E‐520 digital camera with a 35 mm macro lens or by mounting the camera on a Wild Heerbrugg dissecting scope. X‐ray, CT scans and histologic analysis of selected tissue samples was also performed. In particular, this study attempts to focus on highlighting the differences between the early fetus compared to the late stage fetuses or adults. Such an atlas should be of use for students, teachers and physicians.
Spatial buffering of ATP by arginine kinase may be critical for Myxococcus xanthus development
Authors: Bohl Thomas Edward , Fraga Dean
Published: June 2021

Previous work suggested M. xanthus contains an arginine kinase (ark) gene that was incorporated into its genome by horizontal gene transfer. This protein is a member of the phosphagen kinase family, which regulates the concentration of the energy‐carrier molecule ATP by catalyzing the reversible transfer a high‐energy phosphate from ATP to another molecule, in this case arginine. In response to starvation, Myxococcus xanthus cells aggregate to form mounds called fruiting bodies containing resistant spores that can survive until conditions improve. When ark is knocked out in M. xanthus the developmental pathway does not proceed normally. However, when M. xanthus cells with ark knocked‐out are exposed to osmotic stress during development, development is partially restored. The goal of this study is to determine whether this enzyme has evolved a novel function that makes it important for development. To test the effect of AK activity, I will insert genes for AKs of different activity into the M. xanthus DNA. These enzymes will provide AK activity, but not any novel functions that the M. xanthus AK may have. I will then observe whether development proceeds normally in these new strains. I am currently confirming the production of the plasmid that will be used to re‐insert the M. xanthus AK into its genome. This research is supported by the College of Wooster Biology department and Copeland Funding.
Control Of Electron Transfer And Catalysis In Neuronal NOS By A Hinge Connecting The FMN And FNR Domains
Authors: Haque Mohammad M. , Fadlalla Mohammed , Aulak Kulwant , Ghosh Arnab , Stuehr Dennis
Published: June 2021

In nitric oxide synthase enzymes (NOSs) two flexible hinge elements connect the FMN domain to the rest of the enzyme and may guide FMN domain interactions with its partner FNR and NOSoxy domains to enable the electron transfers required during catalysis. In our previous study, we found that incorporating the nNOS FMN‐FNR hinge into eNOS increased its NO synthesis activity 4‐fold, decreased uncoupled NADPH oxidation, and supported faster heme reduction (kr), implying that the composition and/or length of the FMN‐FNR hinge is important for determining electron transfer and catalysis. To more systematically investigate the role of the FMN‐FNR hinge we constructed mutants in nNOS that either shorten or lengthen the hinge by 2, 4, and 6 residues. We found that FMN‐FNR hinge length helps determine electron flux through the nNOS flavoprotein domain. Shortening the hinge inhibited electron flux through both the calmodulin (CaM)‐free and CaM‐bound enzymes, while lengthening the hinge relieved the repression on electron flux that is normally present in the CaM‐free enzyme, and has either no impact or was deleterious for electron flux through the CaM‐bound enzyme. The nNOS kr was also sensitive to FMN‐FNR hinge length. Small changes in hinge length were tolerated, while changes beyond 2 or 4 residues were deleterious to kr, and also decoupled nNOS NADPH consumption from NO synthesis. Supported by NIH GM51941 & HL63744.
Molecular nanoenvironment of the mitochondrial presequence translocase
Authors: Mehnert Carola S. , Gebert Michael , Oeljeklaus Silke , Pfanner Nikolaus , van der Laan Martin
Published: June 2021

The model that membrane proteins form large, highly organized networks instead of floating freely in the lipid bilayer, is just beginning to develop. In an environment as protein rich as the inner mitochondrial membrane, one has to analyze the whole protein network in order to fully understand fundamental mechanisms like protein translocation and oxidative phosphorylation. Molecular machines like the presequence translocase of the inner mitochondrial membrane (TIM23) are a central part of these networks. Analysis of its interactions with high affinity chromatography followed by mass spectrometry gave first impressions of the complex components of the network, but lacked quantitative information. A strategy to obtain this information, firstly focusing on TIM23, was to calibrate the analysis of isolated complexes with defined amounts of in vitro synthesized proteins. The protein clusters found comprised the respiratory chain complexes, metabolite carriers, dehydrogenases and the constituents of TIM23. Interesting new stoichiometric interactors were the ADP/ATP carrier AAC2 and the protein Mgr2, which appears to be a new core component of the translocase.
Modeling Dynamic Regulation of Mitochondrial free Ca2+: Effects of Ca2+ Sequestration and Precipitation
Authors: Pradhan Ranjan K , Blomeyer Christoph A , Bazil Jason , Camara Amadou K.S. , Stowe David F , Dash Ranjan K
Published: June 2021

One of the most intriguing features of cardiac mitochondria is their ability to accumulate, retain and release enormous amount of Ca2+ via sophisticated Ca2+ transport and buffering systems. Mitochondrial free Ca2+ ([Ca2+]m) is mainly regulated by integrated function of Ca2+ uptake and extrusion pathways and Ca2+ sequestration and precipitation mechanisms. In spite of significant studies on the kinetics and regulation of mitochondrial Ca2+ transport systems, the mechanisms involved in mitochondrial Ca2+ sequestration and precipitation remain obscure. Here we developed a detailed computational model by integrating our recent biophysical models of cation transporters and a novel Ca2+ sequestration mechanism into our existing model of mitochondrial bioenergetics to quantitatively understand the dynamic regulation of [Ca2+]m. Experiments were conducted to measure time course of [Ca2+]m, [Ca2+]e, [NADH]m and pH in guinea pig heart mitochondria suspended in buffer media subjected to incremental concentrations of CaCl2 (0–40 μM) and NaCl (0–20 mM). Model analyses of the data suggest (1) with a constant Ca2+ buffering capacity, it is not possible to explain the dynamics of [Ca2+]m, (2) [Ca2+]m is largely influenced by a Ca2+‐dependent Ca2+ sequestration mechanism and least affected by Ca2+‐phosphate precipitation and, (3) there may be additional pathways for Ca2+ uptake (RaM), apart from the Ca2+ uniporter.
Alterations in mitochondrial function in fibroblasts from patients with Leigh Syndrome French Canadian type (LSFC)
Authors: Bemeur Chantal , Beleac Evghenia , Deschênes Sonia , Rivard Marie-Ève , Coderre Lise , Rosiers Christine Des , Burelle Yan
Published: June 2021

LSFC is a monogenic metabolic disease characterized by 1) cytochrome c oxidase deficiency, resulting from a mutation in the leucine‐rich pentatricopeptide repeat motif containing gene LRPPRC, and 2) episodes of lactic acidosis “crisis” leading to death early in life. The mechanisms responsible for these crises remain to be elucidated. In this study, we used fibroblasts from LSFC patients as a working model to test the hypothesis that impaired mitochondrial function and network dynamics in these cells may predispose them to premature death. Calcium retention capacity (CRC), oxygen (O2) consumption, reactive oxygen species production, mitochondrial membrane potential (ΔΨ) and network morphology were assessed in intact or permeabilized control and LSFC fibroblasts. Compared to controls, LSFC fibroblasts showed multiple abnormalities under basal condition, including decreased CRC (36%), O2 consumption (30–59%), ΔΨ (67%) and increased mitochondrial fission. In addition, nutrient overload, which induces premature death of LSFC fibroblasts (FASEB J 2011 25:722.15), exacerbated mitochondrial fission in these cells. Together, these results suggest that mitochondria from LSFC fibroblasts are dysfunctional and this may limit the capacity of these cells to maintain homeostasis, particularly under conditions of nutrient overload. (Supported by: Association de l'acidose lactique and CIHR Emerging Team Grants)
Mitochondrial Biogenesis and Increased Uncoupling Protein 1 in Brown Adipose Tissue of Mice Fed a Ketone Ester Diet
Authors: Srivastava Shireesh , Kashiwaya Yoshihiro , King M Todd , Baxa Ulrich , Tam Joseph , Niu Gang , Chen Xiaoyuan , Clarke Kieran , Veech Richard L
Published: June 2021

We investigated the in vivo physiological responses to a diet in which D‐β‐hydroxybutyrate – (R)‐1,3 butanediol monoester (ketone ester, KE) replaced equicaloric amounts of carbohydrate in eight week old male C57BL/6J. The KE‐fed group had blood D‐β‐hydroxybutyrate (β HB) levels that were much greater than that achieved with high fat ketogenic diets. Voluntary food intake reduced dose‐dependently with KE in the diet. Feeding the KE diet for a month significantly increased the number of mitochondria, uncoupling protein 1 (UCP1), PPARγ, PGC‐1α as well as Sirt1 in the interscapular brown adipose tissue (IBAT). The KE group also had significantly greater 18F‐fluorodeoxyglucose (FDG) uptake in IBAT, indicating functional activation of the tissue. The ketone fed mice had greater plasma leptin levels and increased sympathetic nervous system activity to IBAT. KE‐fed mice exhibited elevated resting energy expenditure, but no difference in the total energy expenditure or body weight. The quantitative insulin‐sensitivity check index (QUICKI) was also significantly greater in the KE group. These results demonstrate KE as a potential anti‐obesity supplement.