bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of red pepper spice and turmeric on inflammation, and oxidative stress in overweight females: a metabolomics approach
Authors: Nieman David C , Kam Lynn , Knab Amy , Shanely R. Andrew
Published: June 2021

Red pepper spice (RP, capsaicin) and turmeric (TM, curcumin) are used as flavorings in foods and for medicinal purposes. Utilizing a randomized, doubled‐blinded, placebo‐controlled, crossover design (2‐wk washout), 4‐wks supplementation with RP (1 g/d) or TM (2.8 g/d) was tested for influences on inflammation and oxidative stress in 62 overweight/obese (BMI ≥ 27 kg/m2) females (40–75 y) with systemic inflammation (CRP ≥ 2.0 mg/L). Overnight, fasted blood samples were collected pre‐ and post‐supplementation, and analyzed for oxidative stress (F2‐isoprostanes, oxidized LDL), inflammation (CRP and 7 inflammatory cytokines), and metabolic profiles using gas chromatography‐mass spectrometry with multivariate partial least square discriminant analysis (PLS‐DA). Pre‐to‐post supplementation measures of inflammation and oxidative stress for both RP and TM did not differ when compared to placebo (all interaction effects, P>0.05), and global metabolic difference scores calculated through PLS‐DA were non‐significant (both spices, Q2Y < 0.40). These data indicate that 4‐wks supplementation with RP or TM at high culinary levels does not alter oxidative stress or inflammation in overweight/obese females with systemic inflammation, or cause a significant shift in the global metabolic profile (which may be more apparent when measured acutely).

Funding, McCormick Science Institute
Start Healthy, Stay HealthyTM: A Nestle Nutrition Initiative to establish healthy eating habits early in life
Authors: Reidy Kathleen , Deming Denise M , Callen Cheryl , Saavedra Jose
Published: June 2021

In response to the growing number of very young overweight children in the US and the poor dietary patterns, beginning in the first 2 years of life, identified through the Nestle Feeding Infants and Toddlers Study (FITS), Gerber launched the Start Healthy, Stay HealthyTM (SHSH) initiative, an integrated nutritionally and developmentally appropriate guidance system of products, education and services. SHSH reaches over 90 percent of new mothers in the US and communicates the importance of teaching healthy eating habits from the start. Findings from FITS were published and widely communicated to help support broad public health initiatives. Gerber products were reformulated to meet needs identified in FITS including providing more fruits, vegetables, whole grains and healthy fats and reducing sugar and sodium. Health care providers and new mothers in the US are provided with stage‐based nutrition advice and guidance through literature and online tools. Each month, there are more than 600,000 visits to Gerber.com and 60,000 downloads of healthy menus. Combining all vehicles, we estimate that the SHSH message of healthy eating is seen hundreds of millions of times. Funded by Nestle Infant Nutrition.
System Dynamics Model Simulated Consumer and Supplier Responses to Sugar‐Sweetened Beverage Taxes
Authors: Xue Hong , Chen Hsin-jen , Hobbs Benjamin F , Igusa Takeru , Wang Youfa
Published: June 2021

Background

Sugar‐sweetened beverage (SSB) taxes have been proposed to contribution to reducing the obesity epidemic in the US. Using a systems dynamics approach, we assess changes in SSB supply and demand in a dynamic process.

Methods

A systems dynamic model simulates the interactions and dynamics of consumer and supplier responses to an SSB tax at the aggregate level.

Results

Our model predicts that a 20% tax‐induced price increase will initially cause an average daily reduction of 2.6 oz per capita SSB consumption. The reduced consumption will lead to increasing stock due to inelastic supply in the very short run. Suppliers will tend to respond by reducing both production and sales price. Consequently, price will increase first and then drop quickly accompanied by positive SSB stocks in the long run, reflecting the nonlinear tax effects and the dynamics in an equilibrium restoration process. After a sharp initial drop, SSB consumption will rebound and then show a pattern coinciding with the changing price. As a result, the long‐run impact upon SSB consumption is less than expected.

Conclusions

Existing studies, which are predominately small and short‐term, may have overestimated the effect of SSB tax on reducing SSB consumption. Imposing SSB tax without accounting for the market structure and the dynamic responses of consumers and suppliers may generate unexpected results.

Grant Funding Source: NIH/NICHD (U54 HD070725‐01, 1R01HD064685‐01A1) and NIDDK (R01DK81335‐01A1)
Simultaneous Analysis of B‐Vitamins in Human Milk
Authors: Hampel Daniela , Allen Lindsay H.
Published: June 2021

Poor maternal intake of B‐vitamins during lactation can result in both maternal depletion and infant deficiency, with associated health risks. Little is known about infant requirements; recommendations are generally based on Adequate Intakes (AI), which have been estimated by analysis of few samples using outdated and time consuming methods. To enable the simultaneous analysis of thiamin, riboflavin, FAD, nicotinamide and pyridoxal in human milk, we have developed a rapid method based on Ultra‐Performance‐Liquid‐Chromatography Tandem Mass‐Spectrometry (UPLC‐MS/MS). Samples were subjected to protein precipitation and removal of non‐polar constituents by diethyl ether prior to analysis. Quantification was done by multiple point internal standard analysis. The standard addition method determined recovery rates for each vitamin (70 – 110%). Analysis of 20 human milk samples from different countries revealed that the vitamin concentration in human milk varies by geographic origin (p‐value < 0.05) and only vitamin B2 concentration met the DRI values in all regions. These analyses will be expanded to additional samples and populations.

Vitamin [mg/L]
DRI
USA median
Cameroon median
China median
India median

Thiamin
0.2
0.06
0.12
0.03
0.03

Riboflavin + FAD
0.35
0.47
0.47
0.32
0.25

Nicotinamide
1.8
1.08
0.16
0.08
0.30

Pyridoxal
0.13
0.04
0.28
0.36
0.31
Human milk oligosaccharides enhance the growth of Staphylococci
Authors: Hunt Katherine M , Preuss Janina , Nissan Caroline , Davlin Charles A , Williams Janet E , Richardson Adam D , McGuire Michelle K , Bode Lars , McGuire Mark A
Published: June 2021

Human milk oligosaccharides (HMO) are largely non‐digestible glycans that are abundant in human milk. Studies show that these compounds likely influence the infant's gastrointestinal microbiome; however, no work has been conducted to determine if HMO also interact with the bacterial communities present in a woman's milk. We previously reported a positive correlation between the relative abundance of Staphylococci and total HMO content in human milk. To further investigate the potential effects of HMO on Staphylococcus growth in milk, strains of S. epidermidis and S. aureus were isolated from human milk. Results indicate that addition of HMO (10 g/L) to cultures grown in minimal medium or infant formula enhanced growth of both Staphylococcal strains. However, when compared with HMO content of fresh media, there was no reduction of HMO content in culture supernatants collected after bacterial growth. These results indicate that HMO stimulate growth of Staphylococci but do not act as nutrient substrates for growth. Supported by NIH R00DK078668 (LB), P20 RR15587 (MAM) and P20 RR016454 (MAM), and the Institute for Bioinformatics and Evolutionary Studies (IBEST).

Grant Funding Source : NIH P20 RR15587
Understanding how participating in a food‐aid program in rural Guatemala alters household dietary choices
Authors: Jensen Melissa L , Frongillo Edward A , Leroy Jef , Blake Christine E
Published: June 2021

There is growing concern that food‐aid programs may contribute to overweight and obesity, but the factors that determine households’ decisions regarding food quality and quantity in the context of food aid are not well understood. We studied these decisions using the community randomized design for Programa Comunitario de Diversificación Alimentaria (PROCOMIDA) in Guatemala, part of Preventing Malnutrition in Children Under Two Years of Age Approach. PROCOMIDA provides food rations (rice, beans, oil, and corn‐soy blend), behavior‐change communication, and health‐sector strengthening. We conducted semi‐structured interviews and six focus groups with 63 households in six villages participating and not participating in the program. Analysis was done using thematic coding based on a priori and emergent codes. Major themes that emerged were: availability of foods, skills in food preparation, knowledge of health benefits of certain foods, and economic burden. PROCOMIDA families (compared to control) reported higher consumption frequency of caloric foods provided by the program (rice, red beans, and oil) and of foods indicative of dietary quality (local plants, vegetables, chicken, and eggs). The interview data were crucial for understanding these differences. Participating in PROCOMIDA altered household dietary choices, and affected the factors that influence these choices.
Phytochemicals and cellular redox potential: Variations in measurement of glutathione levels using three assays
Authors: Marisiddaiah Raju , Wiener Doris , Gong Xiaoming , Rubin Lewis P
Published: June 2021

Purpose

Glutathione (GSH) is the principal intracellular redox couple. Several methods have been devised to measure GSHtot, GSHreduc and GSHoxid (GSSG) in biological samples. However, different techniques and assay conditions can yield conflicting results.

Methods

We measured the GSH redox couple in normal and tumor cell lines using three methods. In some experiments, we compared the GSH couple ±lycopene or lutein. We examined two methods involving fluorimetric or luminometric detection and a spectrophotometric GR:DTNB (enzymatic) recycling method.

Results

The luminometric and spectrophotometric assays consistently yielded GSHred >> GSSG (the physiologically anticipated result). However, the fluorimetric assay yielded >90% of GSHtot as GSSG. An important element in this technique is use of perchloric acid (PCA) protein precipitation to prevent enzymatic degradation of GSH to GSSG.

Conclusion

The discrepancies among glutathione assay methods may result from use of a powerful oxidizing agent (PCA), causing artificial GSSG generation. The GSH:GSSG couple is an important target of phytochemical action, including carotenoids and flavinoids. More consistent measurements of GSH homeostasis should clarify biological effects.

Grant Funding Source : NIH, USF
Household food insecurity affects school children's growth in body mass index
Authors: Burke Michael P , Frongillo Edward A , Jones Sonya J , Bell Bethany A
Published: June 2021

Household food insecurity is associated with greater growth in body mass index (BMI) for some children, but no study has examined its association with school‐aged children's growth in BMI during middle childhood. We examined the effect of household food insecurity on children's BMI trajectories using the Early Childhood Longitudinal Study Kindergarten cohort at kindergarten, 3rd, 5th, and 8th grades. We used the 2000 CDC growth charts to construct BMI z‐scores at each time point, and modeled BMI z‐score as a function of food security status and potential confounders using growth‐curve models stratified by gender. Children in food‐insecure households at kindergarten had significantly lower BMI (0.15 SD units) than children in food‐secure households, but children in food‐insecure households gained significantly more BMI over time, resulting in no difference in BMI between food‐insecure and food‐secure children at 8th grade. The stratified analysis showed a similar pattern for girls and boys. Our study shows that food insecurity differentially affects children's growth in BMI during middle childhood, suggesting children exposed to food insecurity may be on a higher BMI trajectory as they move into late adolescence than food‐secure children. Funded by the University of South Carolina.
Perceptions of the local food environment among low‐income residents of Athens, Georgia
Authors: Wilson Sarah , Lee Jung Sun
Published: June 2021

Previous food environment research has primarily focused on objective measures of food access to find structural explanations why some people are unable to follow the dietary recommendations. This study aimed to better understand subjective measures of food access from the perspective of low‐income individuals from a college town in a persistent poverty county in GA. Qualitative in‐depth interviews were conducted in a convenience sample of low‐income housing residents in Athens, GA (n = 28, mean age 46.6±13.5, 86% female, 82% black). Interviews assessed how respondents thought about their food access, produce acquisition, food choice, and shopping behavior. Each interview was tape‐recorded, transcribed, and analyzed. Participants used multiple food resources to obtain food. Qualitative analysis showed that the patterns of food resource use in the study sample were complicated and influenced by 7 interrelated factors: money and other resources to obtain food, food resource characteristics, transportation, health and eating healthy, household composition, and daily schedule. These findings suggest that subjective measures of food access are more complicated than what objective measures may suggest, and can provide a more complete understanding on the food environment and its role on people's food related behaviors and health.

Grant Funding Source : This study was funded by ADA Foundation's Amy Joye Memorial Research Award.
Engineering Controls to Reduce Formaldehyde Exposures: What works, what doesnˈt, and why?
Authors: Demer Frank R.
Published: June 2021

Formaldehyde, an irritant, sensitizing gas and known human carcinogen, is widely used as formalin for cadaver preservation in gross anatomy laboratories where inhalation exposures are often excessive and adverse symptoms are prevalent. Until formaldehyde can be completely eliminated from the preservation process, engineered ventilation controls are the most critical aspect of formaldehyde hazard control in these environments. Basic, related industrial ventilation design principles will be discussed including dilution ventilation, enclosing, capturing and ductless local exhaust hoods, slots, plenum, effective zone of capture, baffles and supply air delivery. These proven, established design principals will be compared to the assortment of engineering methods that have been employed and described by numerous investigators with varying degrees of success. Ancillary concerns of maintenance, use, ergonomics, specimen desiccation, noise and economic considerations will also be addressed. Attendees will become conversant with basic gross anatomy lab ventilation concepts and approaches to better advocate for effective lab design, maintenance and operation at their institution.
TMEM166, a transmembrane protein, regulates cell autophagy and apoptosis in focal ferebral ischemia
Authors: Zhou Changman
Published: June 2021

TMEM166 is a lysosome and endoplasmic reticulum‐associated membrane protein, which mediates autophagy and apoptosis. In the present study, we investigated the role of TMEM166 following MCAO injury in rats. One hundred and twenty male Sprague‐Dawley rats were randomly divided into 4 groups: sham, MCAO, MCAO+control siRNA, MCAO+TMEM166 siRNA. Outcomes measured include mortality rate, brain edema, BBB disruption, and neurobehavioral testing. Western blotting techniques measure the expression of key pro‐autophagic and apoptotic proteins such as TMEM166, Beclin‐1, cleaved casepase‐3 and Bcl‐2/Bax. TMEM166siRNA treatment signiﬁcantly reduced the mortality rate, cerebral edema, neurobehavioral deficits, and BBB disruption as measured by Evan¡̄s Blue assay following MCAO injury. Immunohistochemical staining and western blot analysis demonstrated an increased expression of TMEM166, Beclin‐1, LC3, cleaved casepase‐3 and Bcl‐2/Bax in the infarction area, which was accompanied with autophagy and apoptosis.
Mother knows best: developmental plasticity during gut development
Authors: Mango Susan , Choi Kaitlyn , Brock Trisha
Published: June 2021

Our group studies organ formation using a simple organ, the C. elegans foregut (or pharynx), that nonetheless faces the same hurdles that confront organs in more complicated animals. Our main focus is the transcriptional processes that establish the foregut from a pool of developmentally‐plastic precursors. I will discuss two aspects of organogenesis:

Pluripotency and cell‐fate acquisition. Early embryonic cells are born pluripotent, but over time their developmental choices become restricted. We study the processes that mediate the transition from developmental plasticity to cell‐fate specification, with a particular focus on the interplay between sequence‐specific transcription factors, chromatin organization and nuclear architecture.

Environmental impacts on development. C. elegans worms are acutely aware of their environment and can sense a wide array of chemicals through 32 chemosensory neurons. These chemicals elicit both short‐term responses to modulate feeding or movement, but also longer‐term effects that alter adult longevity or development. Recently, we found a surprising link between chemo‐sensation and foregut development, which I will describe.
Dynamic information flow during neutrophil polarization
Authors: Wu Lani , Ku Chin-Jen , Wang Yanqin , Weiner Orion , Altschuler Steven
Published: June 2021

While many interactions of biochemical networks have been characterized, the evolving nature of these links and their influence in shaping highly‐coordinated, multistep cellular responses is poorly understood. Here, we tracked the flow of information in the biochemical network responsible for the rapid response of primary human neutrophils to stimuli. We found that not only do paths of information flow rapidly evolve over time, but directionality depends strongly on the observed phenotype. Surprisingly, the set of persistent crosstalk revealed an underlying simplicity: a linear cascade controls signaling activity levels, and a feed‐forward network in the opposite direction controls signaling localization. Our work provides a clear example that a simple flow of information may lay hidden beneath the complexity of “everything‐connects‐to‐everything” biochemical networks.
The interaction of factors required for ER associated degradation (ERAD)
Authors: Brodsky Jeffrey L
Published: June 2021

Many proteins that play critical roles in cellular physiology transit through the secretory pathway, and a significant percentage can fold slowly or inefficiently. Because unfolded proteins compromise cellular function and trigger apoptosis, it is critical that these proteins are recognized and destroyed. Fortunately, once selected by chaperones, defective secreted proteins can be removed via a process termed ER associated degradation (ERAD). During ERAD, polypeptides are delivered from the ER, ubiquitinated, and destroyed by the proteasome. By using a variety of models, many of the critical players in this pathway have been identified and their functions discerned. However, it is likely that there are substrate‐specific modifiers of ERAD and factors that act redundantly with one another that remain unknown. Because ERAD has been linked to many human diseases, we propose that ERAD modifiers might, in turn, be disease modifiers. To this end, we have used yeast‐based expression systems to dissect the ERAD pathway for disease‐causing proteins and to identify uncharacterized factors that modulate ERAD. Our studies have been complemented by in vitro systems that have allowed us to dissect at which step in the ERAD pathway specific factors act.
Development of Streptomyces Bacteria as Lignocellulose Biorefineries
Authors: Sello Jason Kelby
Published: June 2021

The search for renewable energy sources that are alternatives to fossil fuels is critically important. A validated strategy in this context is the use of microorganisms to convert plant biomass into high‐value biofuels. Microbial conversion of the cellulose and hemicellulose components of plant biomass into biofuels is at the vanguard of bioenergy technology. An inherent limitation of this technology is that these carbohydrates represent only 60–70% of plant biomass. The remaining component of plant biomass, lignin, is under‐utilized in part due to its highly stability. Currently used fuel‐producing microorganisms cannot degrade this heterogeneous, aromatic polymer. The efficiency of microbial conversions of plant biomass into biofuels can only be maximized if cellulose, hemicellulose and lignin are all consumed. While fungi have been the foci of most studies of lignin catabolism, bacteria are also have this capability. Given the utility of bacteria in biotechnology and the ease with which they can be genetically engineered, studies of bacteria that degrade and consume lignin are particularly valuable. Prominent among the ligninolytic bacteria are members of the Streptomyces genus. This talk will describe our progress in understanding the catabolism of the lignin component of plant biomass by Streptomyces bacteria and our efforts to engineer these organisms as lignocellulose biorefineries.
Biochemical reconstitution and resolution of lipid flippase activities required for protein glycosylation in the ER
Authors: Menon Anant K
Published: June 2021

The oligosaccharide donor for protein N‐glycosylation is Glc3Man9GlcNAc2‐PP‐dolichol. This lipid is required in the lumen of the endoplasmic reticulum (ER). However, its biosynthesis is initiated on the cytoplasmic face of the ER necessitating transbilayer movement, or flip‐flop, of three lipids across the ER membrane: the biosynthetic intermediate Man5GlcNAc2‐PP‐dolichol (M5‐DLO), and the sugar donors Man‐P‐dolichol (MPD; required also for glycosylphosphatidylinositol (GPI)‐anchoring, O‐mannosylation and C‐mannosylation in the ER lumen) and Glc‐P‐dolichol. Since flip‐flop of these lipids is intrinsically unfavorable, it is likely facilitated by specific transport proteins, or flippases. The predicted flippases have yet to be identified. We report rapid, ATP‐independent flipping of M5‐DLO and MPD in proteoliposomes generated from detergent‐solubilized ER membrane proteins. We show that the M5‐DLO and MPD flippase activities can be biochemically resolved from each other as well as from the ER glycerophospholipid flippase activity, and are highly specific with respect to the structure of the lipid that they transport. These results provide the first clear indication of at least three specific flippase proteins in the ER and establish the basis for their eventual purification and identification.
α‐Tocopherol Supplementation Reduces γ‐Tocopherol‐ Dependent Scavenging Of Reactive Nitrogen Species By Decreasing γ‐Tocopherol
Authors: Pei Ruisong , Leonard Scott W , Traber Maret G , Bruno Richard S
Published: June 2021

γ‐Tocopherol (γ‐T) has a unique function not shared by other vitamin E forms whereby it scavenges reactive nitrogen species (RNS) to form nitro‐γ‐tocopherol (NGT). Because α‐tocopherol (α‐T) supplementation decreases plasma γ‐T, we hypothesized that α‐T supplementation would also inhibit RNS scavenging by γ‐T. Smokers (n = 11) and nonsmokers (n = 10) were provided α‐tocopheryl acetate (150 mg/d) for 6 d and then plasma α‐T, γ‐T, and NGT were measured by LC‐MS on d −6, 0, 6, 13, and 17. Baseline α‐T and γ‐T did not differ between groups, but smokers’ NGT was greater than nonsmokers’ (57 ± 44 vs. 31 ± 10; P = 0.04). α‐T supplementation increased nonsmokers’ and smokers’ α‐T by 41–50%, but decreased γ‐T by 61–70% by d 0 with no differences between groups for either T. Ts were restored to baseline levels by d 6 in both groups. On d 0, smokers’ and nonsmokers’ NGT decreased by 72% and 50%, respectively, with no group differences and was restored to baseline levels by d 6. Timedependent changes in NGT were eliminated after its normalization to γ‐T (NGT/γ‐T), but plasma NGT was correlated (P < 0.01) to γ‐T in nonsmokers (r = 0.41) and smokers (r = 0.55), supporting that γ‐T availability regulates NGT formation. Thus, α‐T supplementation may reduce the potential beneficial effects of γ‐T on RNS scavenging regardless of smoking status and improvements in γ‐T status may increase RNS scavenging capacity.

Grant Funding Source : CT Department of Public Health and NIH DK59576
The Effect of Maternal Anxiety/Depression on Breastfeeding Outcomes: MAVAN (Maternal Adversity Vulnerability and Neurodevelopment) Study
Authors: Adedinsewo Demilade , Fleming Alison S , Steiner Meir , Meaney Michael J , Girard Amy Webb
Published: June 2021

Objectives

We tested the hypothesis that mothers who experience substantial anxiety or depression at different time periods are at risk for reduced initiation, exclusivity and duration of breastfeeding.

Methods

Longitudinal data on mental health and infant feeding were collected on 257 Canadian women from 18–23 weeks gestation through 12 months postpartum. Multivariate logistic regression was used to assess whether scores on the Edinburgh Post‐Natal Depression Scale (EPDS), Hamilton Anxiety Scale (HAMA) and State‐Trait Anxiety Inventory (STAI) were associated with breastfeeding practices.

Results

In adjusted models, a single point increase in HAMA scores measured at 3 months postpartum was associated with an 11% reduction in the odds of exclusively breastfeeding at 6 months [aOR= 0.89, 95% (CI 0.80, 0.99)]; also a single point increase in STAI State and STAI Trait scores measured at 3 months postpartum was associated with a 4% reduction in odds [aOR= 0.96, 95% CI (0.92, 0.99)] and an 8% reduction in the odds of any breastfeeding at 12 months [aOR= 0.929, 95% CI (0.86, 1.00) ] respectively.

Conclusion

Our findings support a relationship between maternal anxiety and reduced breastfeeding but do not show significant associations between maternal depression and breastfeeding practices. Small sample sizes may have limited detection of significant findings.

Grant Funding Source: None
Maternal Hospital Experiences and Exclusive Breastfeeding in the First Six Months among WIC Participants
Authors: Koleilat Maria , Whaley Shannon , Jiang Lu
Published: June 2021

The purpose of this study was to identify how maternal hospital experiences impact breastfeeding exclusivity of the Special Supplemental Nutrition Program for Women, Infants and Children (WIC) participants. A sample of 2015 primarily Hispanic postpartum women, regularly attending WIC clinics in Los Angeles and Orange Counties, were recruited to participate in a telephone survey about their breastfeeding practices. Multiple logistic regression was used to explore predictors of exclusive breastfeeding. After adjusting for well‐recognized confounding factors, results indicated that women who breastfed in the hospital within the first hour after birth, did not formula feed their baby at the hospital, did not receive formula from hospital to take home, and received a telephone number to call if they had questions or needed help with breastfeeding, were more likely to exclusively breastfeed during the first six months after delivery. Not being US born, not working for pay outside the home, intending to breastfeed and previous breastfeeding experience also were predictive of exclusive breastfeeding. These results highlight the importance of hospital practices, as well as intention and experience, on the decision to exclusively breastfeed, and indicate the need for implementing breastfeeding‐friendly practices in hospitals following birth to improve the establishment of exclusive breastfeeding. Funding for this research was provided by the US Department of Agriculture, Food and Nutrition Service through a grant for WIC administered by the California Department of Public Health.
Facilitators and barriers to implementing mother‐to‐mother support groups to improve breastfeeding and complementary feeding practices in the Peruvian highlands
Authors: Shaw Alina Gauntlett , Campos Manolo Quispe , Leon Lia Garcia , Girard Aimee Webb , Golding Lenette
Published: June 2021

Mother‐to‐mother support groups (MtMSGs) provide women with a constructive environment in which they can learn about proper breastfeeding practices. Early initiation and prevalence of breastfeeding in Peru are high; however, exclusive breastfeeding and appropriate complementary feeding practices are sub‐optimal and lead to high rates of malnutrition in Andean communities. Prior to initiating MtMSGs as a key component of their infant and young child feeding (IYCF) programming in Ayacucho, CARE conducted formative qualitative research to determine implementation strategies. Three focus group discussions, 84 doer/non‐doer surveys, and ten key informant interviews took place in four communities. The data indicate that government programs such as Juntos and Vaso de Leche organize social groups for women, which could serve as a barrier to CARE's use of MtMSGs because they incentivize attendance with conditional cash transfers or cans of milk, incentives that CARE does not offer. However, women expressed interest in participating in MtMSGs even if they only received information about ways to improve the nutritional status of their families, as long as the groups had strong leadership. Moving forward, it is important for CARE to engage women in MtMSGs by providing communities with relevant IYCF content and quality group leaders who facilitate productive conversation among participants.

Grant Funding Source : CARE Internatioal
Ethnic disparity in body mass index among 5 to 8 year old children in Hawaii
Authors: Novotny Rachel , Oshiro Caryn ES , Wilkens Lynne R
Published: June 2021

The purpose of this study is to examine disparity in overweight and obesity among children of Asian and Pacific Islander ethnic groups in Hawaii, including the Native Hawaiian‐Asian mixed ethnic group, as compared to White populations in the same Hawaii environment. The study utilizes a cross‐sectional study design and electronic medical record data from Kaiser Permanente Hawaii (KPHI). The sample includes 4608 children, 5 to 8 years old, with a parent who is a member of KPHI health plan. Overall prevalence of overweight plus obesity was 30% (13% overweight, 17% obese). In a mixed regression model, age (positive), female sex (negative), education level of the residential neighborhood (negative) and ethnic group were significantly associated with child body mass index, BMI (kg/m2). Mean BMI (adjusted for all covariates mentioned above) was higher among Pacific Islanders (18.0 + 0.13 kg/m2), Hawaiians (17.3 + 0.14 kg/m2), and Hawaiian‐Asian mixed ethnicity (17.0 + 0.10 kg/m2) as compared to Asian (16.3 + 0.12 g/m2) or White (16.2 + 0.10 kg/m2) (p = 0.0001). USDA/NIFA Award 2008‐55215‐18821
Are obese and overweight children disliked in 1st grade? Teacher and classmate ratings
Authors: Harrist Amanda W. , Cui Lixian , Swindle Taren M. , Page Melanie C. , Hubbs-Tait Laura , Topham Glade L.
Published: June 2021

Few studies directly assess the classroom as a social context for obese children. The current study uses multiple informants to determine (a) whether obese/overweight 1st graders are disliked when compared to healthy‐weight peers and (b) whether teacher and peers concur on the social status of obese/overweight children. Interviews and anthropometric assessments were conducted with 1139 children from 127 classes in 29 rural schools. Children rated how much they liked to play with each classmate. Teachers rated how well‐liked and disliked each child was, and the difference computed. ANOVAs compared classmate liking among Obese (BMI%≥95), Overweight (BMI%≥85), and Healthy Weight (BMI%<85) groups. Both ANOVAs revealed between‐group differences, F(2,1137) = 9.10, p < .0001, and F(2,1067) = 4.71, p < .009, for peer‐ and teacher‐ratings, respectively. LSD comparisons showed overweight children are more disliked than healthy weight children (according to peers, p < .009), and obese children are more disliked than both overweight children (teacher‐report, p < .008) and healthy weight children (according to peers and teachers, ps < .0001 and .008). Regression of teacher ratings on peer ratings and peer‐rating‐by‐weight shows a significant interaction (β = .30, p = .05), such that there is more concordance between peer‐ and teacher‐ratings when evaluating obese children than other children. Funding: USDA 2004‐05545.
Modulation of the metabolism of the carcinogen PhIP in rats by cruciferous and apiaceous vegetables
Authors: Kim Jae Kyeom , Chen Chi , Gallaher Daniel D , Peterson Sabrina
Published: June 2021

Cruciferous and apiaceous vegetables modulate biotransformation enzymes that activate and detoxify carcinogens and may be chemopreventive. Here, we determined in rats the effects of these vegetables supplemented alone or in combination on activation and detoxification of PhIP (2‐amino‐1‐methyl‐6‐phenylimidazo [4,5‐b]pyridine; a carcinogen found in char‐grilled meat). For 7 days we fed male Wistar rats AIN‐93G diet, cruciferous diet (21% cruciferous, wt/wt), apiaceous diet (21% apiaceous vegetables), or combination diet (10.5% each cruciferous and apiaceous vegetables). On day 6, we injected rats with PhIP (10 mg/kg body weight), collected urine for 24 hr, then collected tissues. The cruciferous diet increased liver CYP1A1 and CYP1A2 activities (p < 0.05); these activities were not changed by the other diets. Using a metabolomics approach and UPLC‐TOFMS, urinary PhIP metabolites were analyzed. Consistent with the CYP1A induction, the cruciferous diet increased N2‐OH‐PhIP and 4′‐OH‐PhIP. The apiaceous diet decreased 5‐OH‐PhIP, a biomarker of PhIP‐DNA adducts. The apiaceous diet increased methylated PhIP metabolites. We detected a novel methylated PhIP metabolite not previously reported in rats and in much higher abundance than reported in mice. Apiaceous may enhance detoxification by increasing methylation; the importance of methylation in PhIP detoxification warrants further investigation.

Grant Funding Source : Healthy Foods, Healthy Lives Institute, University of Minnesota
Next generation sequencing of the washed milk fat globule transcriptome
Authors: Lemay Danielle G , Ballard Olivia A , Horseman Nelson D , Morrow Ardythe L , Nommsen-Rivers Laurie A
Published: June 2021

Milk fat globules (MFG) contain cytoplasmic crescents, which are a rich source of lactocyte mRNA. Our aim was to characterize the transcriptome of washed human MFG using Next Generation Sequencing (NGS). Fresh milk was collected from 7 predominately breastfeeding women (2–172 d postpartum) and centrifuged at 15,000g for 10 minutes. The lipid layer was washed twice in PBS to purify the MFG. Poly(A)RNA was extracted and sequenced (Illumina HiSeq2000), averaging 15.3 million 50bp single reads per sample; 27,294 unique transcript variants were expressed, comprising 16,924 unique genes. Blind clustering analysis revealed a distinct transcriptional profile for the participant recovering from mastitis. Functional analyses revealed key genes expressed in the lactocyte that are not yet functionally annotated. The unprecedented dynamic range of NGS enabled us to determine that the top 5 abundant milk protein genes contribute 40% of the mRNA, suggesting that minor abundance transcripts may not be actively down‐regulated by altered transcription factor binding or chromatin modification, but instead by dilution, a mechanism by which lactocytes could dramatically alter phenotype by active up‐regulation of a few key genes. As the first NGS of the human MFG, these data will inform future applications of this powerful tool in lactation research. Funded by Cincinnati Diabetes and Obesity Center (LAN‐R) and NICHD (ALM).
Endotoxin‐stimulated hepatic stellate cells promote survival of hepatocytes in endotoxemia by inducing endoplasmic reticulum stress and autophagy
Authors: Gandhi Chandrashekhar R , Huang Chao , Stolz Donna B
Published: June 2021

Endoplasmic reticulum (ER) stress and autophagy are generally utilized by cells as survival mechanisms. However, cells undergo apoptosis when these processes are excessive or sustained. Our electron microscopic and biochemical analyses demonstrate that endotoxemia‐induced ER stress and autophagy in rats at 6h resolve at later time. We hypothesized that hepatic stellate cells (HSCs) located adjacent to hepatocytes may play a critical role in this phenomenon. Indeed, cell culture assays revealed ER stress and autophagy in hepatocytes challenged with endotoxin‐stimulated HSCs (Endo/HSC). However, inhibition of autophagy or proteosomal activity by 3‐methyladenine and MG132, respectively, causes profound apoptosis of Endo/HSC‐challenged hepatocytes. Further, hepatocytes subjected to oxidative stress during Endo/HSC challenge undergo excessive apoptosis. At the molecular level, LPS‐stimulated HSCs express interferon‐â (IFNâ) and TNF‐á, which induce ER stress/autophagy but not apoptosis of hepatocytes. Our results indicate that HSCs impart protective effect on hepatocytes by inducing ER stress/autophagy during endotoxemia. Inhibition of autophagy by mediators released in the hepatic microenvironment or a “second hit” with Kupffer cell/neutrophil‐derived factors such as reactive oxygen species might be a critical mechanism of liver failure. Support: VA Merit Review Award; NIH PO1A1081678
Mdx mice have a defect in autophagy that is restored by rapamycin‐loaded nanoparticle treatment
Authors: Li Allison Jinquan , Bibee Kristin P. , Marsh Jon N. , Weihl Conrad C. , Wickline Samuel A.
Published: June 2021

Duchenne Muscular Dystrophy (DMD) is genetic disorder caused by mutations in dystrophin, a cytoskeletal protein in muscles, leading to progressive muscle wasting and ultimately death in the second or third decade of life. The current standard of care for DMD patients is corticosteroid therapy which slows down the natural progression of the disease but causes unwanted side effects. Our lab's previous studies of therapeutics in an in vivo DMD model has demonstrated that mdx mice treated with rapamycin‐loaded nanoparticles showed an increase in strength that was not observed with oral rapamycin treatment. Because rapamycin is known to induce autophagy, we assayed for autophagy in mdx mice treated with rapamycin‐loaded nanoparticles. Western blot analysis of LC3B‐II, the processed form of a protein used in autophagy, suggests that there is a previously unknown defect in autophagy in mdx mice, as shown by a lack of LC3 3B‐II accumulation after blockade of autophagic flux by colchicine (Fig. 1A). Rapamycin nanoparticle treatment rescues autophagy to levels comparable to the control (Fig. 1B), suggesting that defective autophagy may contribute to the physical manifestations of muscular dystrophy in mdx mice and that restoration to normal levels may lead to the observed strength increase. Supported by NIH grant (R01 AR056223 to S.A.W.).
Biochemical properties of highly neuroinvasive prion strains
Authors: Sigurdson Christina J , Bett Cyrus , Joshi-Barr Shivanjali , Lucero Melanie , Trejo Margarita , Liberski Pawel , Kelly Jeffery , Masliah Eliezer
Published: June 2021

Prion diseases are fatal neurodegenerative diseases caused by the conformational conversion of the cellular prion protein, PrPC, into an aggregated, β‐sheet rich isoform, PrPSc. Prion pathogenesis can vary dramatically depending on the strain, thought to be conformational variants of PrPSc, yet the structural basis for the differences in pathogenesis in unclear. Using an array of mouseadapted prion strains, here we define the neuropathology and biochemical features of prion strains that efficiently or poorly invade the CNS from their peripheral entry site. In brain sections, we find that the highly neuroinvasive prion strains primarily form diffuse aggregates that do not bind to the amyloid binding dye, Congo red. Biochemically these aggregates are conformationally unstable in denaturing conditions. These neuroinvasive strains also efficiently generate PrPSc over short incubation periods. In contrast, the poorly neuroinvasive strains formed dense, Congo red binding aggregates that were conformationally stable. Our findings indicate that the most neuroinvasive, efficiently spreading strains are also the least conformationally stable, and support the concept that the unstable nature of the most rapidly converting prions may be a feature linked to their efficient spread into the CNS.
MITOCHONDRIAL DNA MUTATIONS IN LOCUS CERULEUS NEURONS OF ALZHEIMER DISEASE BRAIN
Authors: trikamji bhavesh v , Miller Bradley
Published: June 2021

Context

There is increasing evidence linking mitochondrial genetic mutations to neurodegenerative diseases such as Alzheimer's disease (AD). The goal of the study is to test the hypothesis that mutations are present in the mitochondrial DNA (mtDNA) of neurons in areas of the brain that are affected early in AD, including the brainstem.

Design

We used laser microdissection to isolate single neurons from memory processing and influencing areas of AD and control brain tissue. The mtDNA was selectively amplified using the whole genome amplification and polymerase chain reaction techniques. Mutations were identified by direct sequencing of PCR products.

Results

We found a significantly higher percentage of mtDNA‐mutation‐containing neurons in the brainstem monoaminergic systems versus the hippocampal and cerebral cortices.

Conclusion

We have performed a detailed examination of mtDNA in the areas involved in memory processing of AD brain. We find that the mutational burden is highest in areas affected very early in AD and lowest in areas affected later. While it remains to determine whether mtDNA mutations have a causal role or are correlative, we have shown that mtDNA damage in the monoaminergic systems of the AD brain is present at the earliest stages of disease.
The sympathetic neuron autonomous role of Egr3 in sympathetic target tissue innervation and gene expression
Authors: Quach David Hon , Gao Xiaoguang , Gruner Katherine , Tourtellotte Warren
Published: June 2021

Egr3 is a transcription factor that is essential for sympathetic nervous system (SNS) development. Our lab has previously shown that mice with germline loss of Egr3 have profound SNS defects. However, Egr3 is expressed in other cell populations in addition to sympathetic neurons, so it is still unclear whether Egr3 has a critical role specifically in sympathetic neurons. In the present study we show that Egr3 expressed in sympathetic neurons is essential since mice with specific deletion of Egr3 in sympathetic neurons recapitulated the SNS abnormalities seen in the germline Egr3 deficient mice. We also further examined how Egr3 affects sympathetic innervation into target tissues in vivo by utilizing a unique mouse model paradigm. This paradigm enabled us to trace axons from only a small subset of sympathetic neurons allowing the detailed visualization of the innervation pattern of individual axons in target tissues. Since Egr3 is a transcriptional regulator of gene expression we employed microarray analysis to elucidate the downstream genes it modulates in order to control SNS development. We identified several genes involved in both neuron development and cytoskeleton organization. Taken together, these results indicate Egr3 has a sympathetic neuron specific role in SNS development that involves modulating downstream genes affecting how sympathetic neurons innervate target tissues.

Support: NINDS, NRSA
Exosites, Allostery, & Active Site in MMP Engagement of Elastin, Collagen, and Heparin from the Matrix
Authors: Van Doren Steven R. , Fulcher Yan , Byrne Todd , Zhao Yingchu , Zhang Fuming , Linhardt Robert , Fields Gregg
Published: June 2021

MMP‐12 and MT1‐MMP digest protease‐resistant elastin and collagen in inflammatory diseases. ProMMP‐7 is activated by glycosaminoglycans (GAGs). How do these matrix components interact with these MMPs? We sought to locate using NMR the binding sites of elastin and collagen triple‐helical peptides upon MMP‐12, collagen upon MT1‐MMP, and heparin fragments upon proMMP‐7. Two remote loops enhance its degradation of elastin substrates. Mutations at both remote loops plus the active site knock down specifically the elastase activity to that of the negative control. A collagen triple‐helical peptide crosses the active site of MMP‐12 at an angle and may separate the peptide chains in the primed positions for one chain to fit into the narrow slot formed by the primed subsites. Solubilized collagen binds a patch across blades III and IV of the β‐propeller of the hemopexin domain of MT1‐MMP. Binding of 6 to 12‐mer pieces of heparin to proMMP‐7 achieves part of the GAG‐dependent activation. The binding site is on the back of the catalytic domain. Adjustments in the interface between catalytic and pro‐domains and activation can then follow, suggesting allosteric communication at long range. Overall, pericellular proteolysis can engage remote surfaces of MMPs. Supported by NIH grants GM57289 and CA98799 and AHA grant 0855714G.
Comparative Functional Morphology of the Head Suspension of Quadrupedal Cats and the Shoulder Suspension of Bipedal Humans
Authors: Osborn Michelle L , Homberger Dominique G
Published: June 2021

Although there exists a general tetrapod Bauplan, major transformations seem to have occurred during evolutionary history. Using biomechanical analyses, we tested our hypothesis that the drastic differences in the mastoid process, nuchal crest (or line), and clavicle of the cat and human are caused by different force regimes acting on the head‐neck‐and‐shoulder complex. In the cat, the head suspension apparatus comprises a nuchal ligament and fascias that suspend the head and that are assisted by a sternocleidomastoid‐trapezius muscle complex. The muscles of the sternocleidomastoid complex attach ventral to the Foramen magnum, while the cleidocervical (clavotrapezius) muscle attaches dorsal to it. In the human, the shoulder suspension apparatus also comprises a nuchal ligament and fascias, which, however, suspend the shoulders and which are also assisted by a sternocleidomastoid‐trapezius muscle complex. The muscles of the sternocleidomastoid complex attach at the level of the Foramen magnum, while the clavotrapezius muscle attaches posterior to it. The particular attachment sites of the muscles are responsible for the force regime of each suspension apparatus, which affects the size of the clavicle. Hence, relatively minor anatomical differences have fundamental constructional and functional consequences with macroevolutionary implications.

Funding: LSU Foundation to DGH

Grant Funding Source: N/A
Increased episodes of anatomy comic strips
Authors: Chung Min Suk
Published: June 2021

Comics are the powerful visual messages to convey immediate visceral understanding in ways that conventional texts cannot. In the present study, author created comic strips (title: Dr. Anatophil) to teach anatomy more interestingly and instructively. To achieve this, funny stories related to the anatomy were collected and then scenarios were written. Based on the scenarios, the four‐frame comic strips were drawn on paper, and then painted on the computer. Humorous comic strips of more than 500 episodes have been elaborated in Korean language. Only 13 comic episodes were translated into English, when the article entitled ¡°Anatomy comic strips¡± was published in the journal, Anatomical Sciences Education on September, 2011. But now 87 English episodes can be seen freely at the homepage (anatomy.co.kr); the number is increasing up to 300 episodes. Owing to the effort of writing and drawing by the experienced anatomist, the searched responses were favorable in general. The encouraged author considers releasing a comic book in the United States to make them more approachable. In addition, the author has started to produce the science comic strips (title: Dr. Scifun) in order to introduce the comical situations encountered by scientists. The new set of episodes is going to be opened soon on the same homepage.