bluuebunny/crossref_metadata_2025 huggingface dataset:
Increasing Cannabis Use Is Associated With Poorer Cigarette Smoking Cessation Outcomes: Findings From the ITC Four Country Smoking and Vaping Surveys, 2016–2018
Authors: Driezen Pete , Gravely Shannon , Wadsworth Elle , Smith Danielle M , Loewen Ruth , Hammond David , Li Lin , Abramovici Hanan , McNeill Ann , Borland Ron , Cummings K Michael , Thompson Mary E , Fong Geoffrey T
Published: June 2021

Introduction

Concurrent use of tobacco and cannabis may impede successful cigarette smoking cessation. This study examined whether changes in cannabis use frequency were associated with smoking cessation.

Aims and Methods

Nationally representative samples of adult cigarette smokers from Canada (n = 1455), the United States (n = 892), England (n = 1416), and Australia (n = 717) were surveyed in 2016 and 2018. In each year, smokers reported how often they used cannabis in the previous 12 months. Reports were compared to determine whether cannabis use increased, remained unchanged, or decreased. Smoking cessation outcomes, measured in 2018, were (1) any attempt to quit in the previous year, (2) currently quit, and (3) currently quit for at least 6 months. Weighted multivariable logistic regression estimated the association between changes in cannabis use and cessation outcomes.

Results

Cigarette smokers who increased their frequency of cannabis use were significantly less likely to be currently quit than noncannabis-using smokers (adjusted odds ratio (aOR) = 0.52, 95% CI = 0.31% to 0.86%); they were also less likely to have quit for at least 6 months (aOR = 0.30; 95% CI = 0.15% to 0.62%).

Conclusions

Smokers who increase their frequency of cannabis use have poorer smoking cessation outcomes compared to noncannabis-using smokers. It will be important to monitor the impact of cannabis legalization on patterns of cannabis use, and whether this influences cigarette smoking cessation rates.

Implications

Cigarette smokers who start using cannabis may be less likely to quit cigarettes compared with smokers who do not use cannabis at all. If smokers who also use cannabis are more likely to continue smoking, it is important to monitor these trends and understand the impact, if any, on smoking cessation in jurisdictions that have legalized cannabis for nonmedical use.
Complementary Medicine Use in Patients with Low Back or Neck Pain: Results of the 2017 National Health Interview Survey
Authors: Koch Anna K , Cramer Holger
Published: June 2021

Objective

Complementary and integrative medicine (CIM), including mind–body medicine (MBM), is a treatment option that has been proved to alleviate symptoms in patients with low back and neck pain.

Methods

Data from the National Center for Health Statistics’ National Health Interview Survey 2017 were used to examine prevalence and predictors of MBM use and consultation of CIM practitioners among patients with low back and neck pain in the American adult population.

Results

A weighted total of 81,671,436 participants (33.1%) reported low back and neck pain. Of those, more participants used mantra meditation, mindfulness meditation, spiritual meditation, guided imagery, and progressive relaxation than did participants without low back and neck pain (all P < 0.001). Spiritual meditation was the most popular (12.6%), followed by mindfulness meditation (6.9%) and progressive relaxation (5.4%). Participants with low back and neck pain consulted practitioners of CIM more often than did those without low back and neck pain (P < 0.001). MBM use was predicted by being female, having a higher educational level, being employed, and living in the Western United States. Consultation of practitioners of CIM was predicted by younger age, being female, not being married or living with a partner, having a higher educational level, being employed, living in the Western United States, and being uninsured.

Conclusions

MBM is a popular treatment option for people with low back and neck pain. Practitioners of CIM are also being sought out by people with such complaints. Further research in this direction is relevant.
Arabidopsis thaliana: A Unique and Powerful Model for Genomic Mutation Accumulation and Chromothripsis
Authors: Fernandes Nancy Lynn , Singh Subha
Published: June 2021

The objective of this study is to increase our understanding of mutation accumulation in multicellular genomes with deficiencies in the DNA damage response regulators employing the model organism Arabidopsis thaliana. We compare and quantify genomic mutations between wild‐type cells and cells defective in global regulator ATR of the DNA damage response mechanism. We have established mutation accumulation (MA) lines for whole genome mutation analysis. Assembly and analysis of the MA line genomes show a spectrum of genome rearrangements as compared to point mutations. Defects in ATR and related repair pathways generate a unique spectrum of mutational events that can be used to predict similar genomic deficiencies in other organisms. A combination of bioinformatics, genomic analysis and a model organism that tolerates mutation accumulation of DNA damage response genes sheds light on how global regulators of the DNA damage response affect overall genomic stability and how defects in these genes contribute to genomic instability. Understanding how global regulators of the DNA damage response affect genomic stability in healthy human cells and how defects in these genes contribute to genomic instability seen in cancer cells requires the knowledge of how and why specific mutation occurs. This study bridges a critical gap in knowledge, how genomes of multicellular organisms respond to genome instability when essential genes involved in the DNA repair pathway are mutated.

Support or Funding Information

National Science Foundation
“Effects of Antisense Oligonucleotide Treatment on Photoreceptor Function in a mouse Model of Usher Syndrome”
Authors: Franceschini Fran Alberto , Amato Russell , Rigo Frank , Hastings Michelle , Lentz Jennifer
Published: June 2021

Usher syndrome (USH) is the most common cause of inherited deaf‐blindness. Depending on the type (I, II, or III), hearing impairment and vestibular dysfunction can be variable, but all Usher patients exhibit a progressive loss of vision due to retinitis pigmentosa (RP). Usher syndrome type 1 (USH1) is responsible for 35 – 45% of all Usher cases and is characterized by severe to profound hearing impairment and vestibular dysfunction at birth, as well as, the development of RP in early adolescence. 6–8% of USH1 are caused by mutations in the USH1C gene, which encodes the protein Harmonin. Harmonin has been shown to play an important role in the development and function of auditory hair cells in the cochlea; however, its role in the retina is unknown. Our lab has produced a knock‐in mouse model containing the human USH1C c.216G>A splicing mutation (216A) responsible for USH1 in Acadian patients of south Louisiana. These mice have profound hearing impairment, vestibular dysfunction, loss of visual function and slow retinal degeneration similar to patients. Recently, antisense oligonucleotides (ASOs) targeting the 216A mutation in these mice have been shown to enhance correct Ush1c gene and Harmonin protein expression, and be efficacious in rescuing hearing and vestibular function when administered by intraperitoneal injection (systemic). However, only marginal improvement in visual function was observed; possibly due to an insufficient concentration of the ASO in the eye. The purpose of this study was to evaluate visual function after an intravitreal (local) ASO treatment.

Rod and cone photoreceptor function was evaluated by scotopic and photopic electroretinogram (ERG) analysis, respectively, in ASO‐treated 216AA mutant and littermate control mice. An increase in scotopic a‐wave amplitude was observed within 3 months of ASO treatment in 216A mutant mice compared with control littermates, indicating an early improvement in rod function. This improvement was observed when the mice were treated at 1, 3 or 6 months of age, suggesting a large temporal window for successful intervention between adolescence and adulthood. An analysis of photopic ERGs showed no differences in untreated 216AA mutant and control littermates, suggesting cone function is not affected in early stages of disease. These data demonstrate the potential of ASOs for the treatment of retinitis pigmentosa associated with Usher syndrome.

Support or Funding Information

This research was supported by grant #1359140 through the National Science Foundation
Validation of a Novel Method for Use in Studies of Iron Status, Brain Function (EEG), and Recognition Memory Performance in Infancy
Authors: Stoyell Sally M. , Nevins Julie E.H. , Orsillo Maisie A. , Canfield Richard L. , Robertson Steven S. , Haas Jere D.
Published: June 2021

Background

Early infancy is a time of peak cortical development when young infants are more susceptible to cognitive deficits from nutritional deficiencies. Previous studies link EEG measures of brain function to behavioral measures during recognition memory tasks in early infancy, but few in the context of nutrition deficiencies. Animal studies have shown that specific nutritional deficiencies affect the brain in targeted areas rather than as a broad cognitive change, but many current studies of nutrition and cognition in human infants only use general measures of cognition.

Objective

Our study is unique in looking at early infant recognition memory, brain function, and iron status. This analysis examines the relationship between behavioral and brain (EEG) measures of memory as a validation of methods that could be applied in subsequent studies of the relationship between infant iron status and cognitive function.

Methods

EEG data were collected from infants (4–6 mo, N=30) during a memory task (Oddball) in which the infants observed novel and familiar stimuli of emotionally neutral female faces. During a related memory behavior task (Paired Comparison), infants viewed two faces simultaneously and the length of infant gaze at each stimulus by stimulus type was measured. Hemoglobin and serum ferritin were measured to assess anemia and iron stores, respectively. The main EEG outcomes were the difference in amplitude and slope of the late slow wave (ΔLSW) between novel and familiar stimuli, a known measure of memory. The percent of time spent looking at the novel versus familiar stimuli (%Nov), as well as the total time spent in attention were the main memory behavior outcomes. Student's t‐tests and regression modeling were used to analyze the association between ΔLSW and %Nov. Age, sex, race, birth weight, and maternal education were assessed as potential confounders in regression models.

Results and Conclusions

Preliminary results show that ΔLSW was significantly associated with %Nov (β = 0.52 ± 0.27; p=.04). These results show that our novel combination of methods successfully measures recognition memory and improves on previous work by using specific behavioral tasks and measures of brain function in the context of infant iron deficiency. This study will inform future work in the fields of nutrition and cognition.

Support or Funding Information

Funded by USDA/CUAES (Hatch #NYC399413) and Cornell Human Ecology Alumni Association; JEHN supported by NSF GRFP
Assessment of Omega‐3s Knowledge on Blood Lipids among Registered Dietitians
Authors: Li Cheng , Palmer‐Keenan Debra
Published: June 2021

The beneficial effects of omega 3 fatty acids (n‐3s) on lowering triglyceride (TG) levels have been well established. For patients with high fasting TG levels, the American Heart Association recommends two to four grams of eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) per day. While n‐3s’ clinical use is well‐documented, incomplete and/or incorrect information regarding their effects on blood lipids is prevalent. The objective of this cross‐sectional study was to assess dietitians’ knowledge of n‐3s and their effects on blood lipids. All Registered Dietitians (RDs) listed in the Academy of Nutrition and Dietetics/Commission on Dietetics Registration database who were not retired as of April 2015 were invited to participate. Structured telephone interviews including two open‐ended questions were used to examine if and what they knew about n‐3s and the effects on blood lipids. Of the eligible RDs, 262 completed the study and were included in the final analyses. Descriptive statistics (frequencies, means and standard deviations) and Chi‐Square tests were performed using SAS (version 9.3). Among the RDs who participated, most were women (95%), non‐Hispanic White (85%), and had a master degree or higher (60%). Mean years of professional practices was 19.3+11.7. Forty percent of RDs identified they specialized (defined as over 50% of time) in medical nutrition therapy (MNT). An assessment of RDs’ general knowledge of n‐3s revealed that, 24% were not able to name any types of n‐3s. Among those who could (n=200), DHA were the most frequently identified (84%), followed by EPA (80%), and ALA (46%). Thirteen percent erroneously identified linoleic acid as one type of n‐3s. When asked if n‐3s affected blood lipids levels, 77% said n‐3s did. However, when asked to specify the types of blood lipids (n=202), only 39% mentioned n‐3s could lower triglycerides. A higher percentage of RDs who specialized in MNT identified n‐3s effects of lowering TGs than those who did not (x2 =6.33; p = 0.0119). Thirty seven percent said n‐3s could decrease low‐density lipoprotein (LDL) and 36% mentioned n‐3s could increase high‐density lipoprotein (HDL), which were not well supported in current literature; in fact some research has shown conflicting results (n‐3 supplements might slightly increase LDL). Further, 14% mentioned n‐3s could decrease total cholesterol. These results did not differ between RDs who specialized in MNT or those who didn't. In conclusion, some RDs generally have knowledge on the types of n‐3s and their effects on lowering triglycerides, but many do not. Since RDs working in MNT are on the front lines of giving nutrition and health recommendations for patients, and their knowledge base was inconsistent, more research‐based education on n‐3s may be needed

Support or Funding Information

United States Department of Agriculture, New Jersey Agricultural Experiment Station Grant Number: NJ14208; (Multi‐State Project NC‐1199)
Pilot Study for Assessing Moderate to Long‐Term Outcomes of the Expanded Food and Nutrition Education Program (EFNEP)
Authors: Auld Garry , Baker Susan , Batchelder Justin
Published: June 2021

Objectives

determine (1) the best communication channel for contacting EFNEP adult graduates; (2) moderate to long‐term (6 or 12 month) self‐reported behavior data; and (3) graduates willingness to provide objective data (BMI, blood pressure).

Methods

Graduates were randomly assigned to be contacted by traditional mail, email, text, or phone call. Upon contact, graduates completed EFNEP's standard behavior checklist as they had completed at pre and post intervention – via web link, pencil and paper, or phone interview, and indicated willingness to provide objective data.

Results

Response rates by communications channel ranged from 4 to 32%; phone call or text from the educator were above 30%. At 6 or 12 months post‐graduation, the score on the 3 behavior checklist scales (nutrition, food resource management, food safety) were all significantly better than the pretest and equal to the posttest scores, suggesting that positive dietary changes were maintained. Respondents “might” or “would” allow collection of BMI (70%), blood pressure (70%), finger prick (55%) or urine sample (60%).

Conclusions

This pilot study provides initial evidence that behavior changes reported at the end of EFNEP interventions are maintained at 6 or 12 months. Graduates willingness to provide objective data will enable EFNEP to strengthen outcome measures and confirm self‐report data to build the evidence base for the program. Using educators who have a relationship with graduates appears to offer the best way to recruit them.

Support or Funding Information

United States Department of Agriculture's National Institute of Food and Agriculture Regional Nutrition Education Centers of Excellence Initiative
Beverage choices among adults and their contribution to nutrient intake
Authors: Parker Elizabeth , Clemens John , Moshfegh Alanna
Published: June 2021

Nationally representative one‐day dietary data from What We Eat in America, NHANES 2011–2012 were analyzed to determine beverage choices of US adults 20 years and older (2394 males; 2407 females) and their contribution to nutrient intakes. Beverage intake data were obtained from an in‐person 24‐hour recall collected using the USDA 5‐step Automated Multiple‐Pass Method. Beverages were categorized into groups as follows: 100% juice, alcoholic beverages, coffee/tea, diet drinks, fruit drinks, milk, soft drinks, other drinks, water. After water (83 +/−0.8%), the top three reported beverages were coffee, soft drinks, and tea (53+/−1.3, 31+/−1.6, and 28+/−1.5%, respectively). In adults, beverages contributed nearly 20% of mean daily energy intake, greater than 40% of vitamin C and total sugar, and about 25% of carbohydrate, vitamin D, riboflavin, calcium, magnesium and potassium. Types of beverages consumed and contribution to energy intake (kcals) and nutrient density (intake/1000 kcal) differed by gender. Males were three times as likely to consume beer (20+/−1.2 vs. 6 +/−0.6%; P<0.01) and more likely to consume soft drinks (35+/−1.6 vs. 27+/−2.0%; P<0.01) as females; females were more likely to consume wine and diet drinks. Mean daily beverage intake (2885+/−98.1 g vs. 2345+/−50.6 g; P<0.01) and energy intake from beverages (485+/−16.4 vs. 309+/−12.0 kcals; P<0.01) were significantly greater in males than females. Females as compared to males had greater nutrient intakes/1000 kcal from beverages for calcium, magnesium, potassium, and phosphorus (P<0.01). Although one out of every five calories consumed by adults comes from beverages, beverage choices vary by gender, impacting nutrient intake. Therefore, beverage choices should be considered when examining diet quality.

Support or Funding Information

This study was funded by the USDA Agricultural Research Service.
Collecting Brand and Product Names in the USDA Automated Multiple Pass Method (AMPM) 24‐hour Dietary Recall
Authors: Steinfeldt Lois C. , Moshfegh Alanna J.
Published: June 2021

Brand and product names collected from respondents in dietary surveys often provide specific characteristics of foods/beverages which can assist in assigning nutrient profiles to those foods/beverages. They can also be used to create direct links between a food/beverage reported by a respondent and a product specific nutrient profile in a food composition database. Using brand and product names reported by respondents can result in reduced processing time and effort and can increase the specificity and amount of detail about foods available from dietary surveys. In order to accomplish this, both the dietary survey collection system and the food composition database need to include brand and product names and respondents need to know the brand and product name of items they report. USDA/ARS is working to obtain branded food product label data in electronic format that can be made available in the USDA food composition database. The Partnership for Public Health: Branded Food Products Database, composed of USDA/ARS, the International Life Sciences Institute North America and the Agricultural Technology Innovation Partnership Foundation was established to increase the knowledge of the nutritional content of the nation's food supply by obtaining comprehensive food composition data from food manufacturers. USDA/ARS included the collection of selected brand and product names in the design and development of the AMPM. The USDA AMPM collects 24‐hour dietary recalls for the What We Eat in America (WWEIA), National Health and Nutrition Examination Survey (NHANES). AMPM uses a research‐based, multiple‐pass approach which has 5 steps designed to encourage complete and accurate dietary recall and reduce respondent burden. The purpose of this research is to describe the use of AMPM brand and product name questions. AMPM questions and responses were analyzed for 15,885 complete and reliable dietary recall interviews in the 2011–2012 WWEIA, NHANES. AMPM questions were identified as asking for brand or product specific responses based on the text of the question. In 88% of the 2011–2012 AMPM dietary recall interviews, respondents were asked at least one question about the brand name of a reported food/beverage. Both days for both males and females averaged three questions about brand names per interview. There were no differences in the percentages (p < .05) between the day 1 and day 2 interviews or between males and females. Overall, 70% of the brand name responses matched a description in the AMPM, 10% of the brand name responses did not match an AMPM description, and 20% of the responses recorded that the respondent did not know. Collection of brand and product names in dietary recalls is becoming more important for producing comprehensive dietary survey data. Their collection in the AMPM interview demonstrates that respondents are able to provide this information.

Support or Funding Information

ARS, USDA
Ancient Whole Grain Gluten‐Free Buckwheat Snacks
Authors: Kahlon Talwinder Singh , Avena_Bustillos Roberto J , Chiu Mei‐Chen M
Published: June 2021

Four kinds of whole grain Buckwheat snacks (gluten‐free, low in fat and salt) were evaluated. The snacks were Buckwheat, Buckwheat‐Turmeric, Buckwheat‐Pepper and Buckwheat‐Ginger. Turmeric and Ginger are very common ingredients of Asian cuisines. Turmeric and ginger have been reported to have health promoting potential, as increase blood flow and prevent joint pain. All the snacks contained 6% corn oil and 2% salt. Snack dough was prepared using 120 mL water for 100 g dry ingredients. About 22 g of snack dough was placed on each side of preheated KrumKake Baker and cooked for 1.75 minutes. Seventy one in‐house volunteers judged Buckwheat‐Ginger snacks significantly higher in Odor/Aroma than Buckwheat‐Pepper snacks. Color/Appearance, Taste/Flavor, Texture/Mouth‐feel and Acceptance were judged to be similar in four kinds of Buckwheat snacks tested. Water activity of all the snacks tested ranged from 0.21–0.32 suggesting that these snacks were crispy and would have good microbial stability. These snacks were quite filling due to their expansion of 3–4 times resulting in high porosity. There were significant differences in color but not in texture of snacks tested. Acceptance of snacks tested was Buckwheat 84%, Buckwheat‐Turmeric 80%, Buckwheat‐Pepper 73% and Buckwheat‐Ginger 70%. These snacks contained only 3–4 ingredients and could be made in any house kitchen or commercial production. Acceptance of 70–84% is very desirable. These healthy nutritious snacks offer choice for all including individuals sensitive to gluten.

Support or Funding Information

USDA‐ARS Base funding
An Inhibitory Role of Piceatannol in Cancer Cachexia‐Associated Lipolysis In Vitro
Authors: Kershaw Jonathan , Kim Kee‐Hong
Published: June 2021

Cancer‐associated cachexia (CAC) is the debilitating “wasting” syndrome observed in many cancer patients, and is the estimated direct cause of death in up to 20% of all cancer mortalities. Although the causes of CAC are complex, increasing evidence suggests that preventing adipocyte lipolysis may preserve both lean muscle and adipose mass. Indeed, adipose loss in CAC is primarily due to increased lipolysis. Currently, there are no effective treatments of CAC. We recently identified piceatannol, a resveratrol analogue, as an anti‐adipogenic small molecule. We further found that piceatannol, unlike resveratrol, inhibits lipolysis in mature adipocytes both in vitro and in vivo. The objectives of this study were to first establish in vitro models of cancer‐associated lipolysis, and then to investigate whether piceatannol prevented lipolysis in CAC‐related conditions. Cancer‐associated lipolysis was modeled in murine 3T3‐L1 adipocytes using both pancreatic cancer‐cell (Panc‐1) conditioned media (CM) and the cachexia‐associated cytokines TNF‐alpha and interleukin‐6. These models significantly increased lipolysis. Of interest, piceatannol lowered cancer‐associated lipolysis by at least 50% in both CM and cytokine induced lipolysis in adipocytes. Molecular analysis revealed that piceatannol induced autophagy‐mediated protein degradation of adipose triglyceride lipase (ATGL), which catalyzes the initial and rate‐limiting step of lipolysis in adipocytes, and comparative gene identification‐58 (CGI‐58), an ATGL co‐activator. Gene expression of ATGL was unaffected by piceatannol treatment, further supporting the hypothesis that piceatannol regulates lipolysis post‐transcriptionally. In addition to revealing the role of piceatannol in reducing cancer‐associated lipolysis, this study characterized the effect of cancer CM on expression of key lipid metabolism machinery. Preventing adipose loss in CAC can enhance chemotherapy response, increase survival outcomes, and improve quality of life. This study provides a theoretical basis for using piceatannol or piceatannol‐rich foods as alternative medicine to supplement cancer treatment.

Support or Funding Information

This research was supported by NIH, 5R03CA184544‐01A1 and the USDA‐NIFA National Needs Fellowship.
Butyrate Plays Differential Roles in Cellular Signaling in Cancerous HCT116 and Noncancerous NCM460 Colon Cells
Authors: Zeng Huawei , Taussig David P , Cheng Wen‐Hsing , Hakkak Reza
Published: June 2021

Butyrate, an intestinal microbiota metabolite of dietary fiber, exhibits chemoprevention effects in colon. However, the mechanistic action of butyrate at the cellular level remains to be determined. We hypothesize that butyrate plays differential roles in cancerous and non‐cancerous cells through signaling pathways regulating histone deacetylation, apoptosis, and cellular survival. We tested this hypothesis by exposing cancerous HCT116 or non‐cancerous NCM460 colon cells to physiological relevant doses of butyrate (0.25–2 mmol/L). Cellular responses were characterized by protein expression (Western blotting), fluorescent microscopy, acetylation, and DNA fragmentation analyses. Upon exposure to butyrate (2 mmol/L) for 72 hours, cell proliferation was reduced by 93% in HCT116 cells, compared to 57% in NCM460 cells. In addition, butyrate treatment led to an induction of apoptosis, histone deacetylation, genomic DNA fragmentation and p21 tumor suppressor expression in HCT116 cells, but to a smaller extent in NCM460 cells. In contrast, butyrate increased the phosphorylation of extracellular‐regulated kinase 1/2 (ERK1/2) in NCM460 cells but not in HCT116 cells. Taken together, the activation of survival signaling in NCM460 cells and apoptotic signaling in HCT116 cells may confer the increased sensitivity of cancerous colon cells to butyrate in comparison with noncancerous colon cells.

Support or Funding Information

This work was supported by USDA‐ARS, CRIS project (5450‐51000‐050‐00D).
Lutein and DHA Co‐localize in Cell Membranes of Brain Regions Controlling Cognition in the Rhesus Macaque
Authors: Mohn Emily S , Matthan Nirupa R , Erdman John W. , Neuringer Martha , Kuchan Matthew J , Johnson Elizabeth J
Published: June 2021

Lutein, a xanthophyll with antioxidant properties, preferentially accumulates in primate brain. Brain concentrations of lutein are associated with higher cognitive test scores and supplementation with lutein improves cognitive performance in older adults. The mechanism underlying this beneficial effect, however, remains unknown. Recent studies suggest the association between brain lutein and cognition may be dependent on brain docosahexaenoic acid (DHA) levels, which are also related to better cognitive function. Furthermore, supplementation with both lutein and DHA has been shown to provide additional cognitive benefits in older adults compared to supplementation with either alone. Therefore, lutein and DHA may function together to influence cognition. Given that both compounds accumulate in membranes, the objective of this study was to determine the co‐localization of lutein and DHA in membranes of brain regions controlling different domains of cognitive function in adult rhesus monkeys (age 7–20 y; n=11). Nuclear, myelin, mitochondrial, and neuronal plasma membranes were isolated from prefrontal cortex, cerebellum and striatum tissue using differential centrifugation with a Ficoll density gradient. Lutein and DHA were measured using high performance liquid chromatography and gas chromatography, respectively. Results document that both lutein and DHA were differentially distributed among nuclear, myelin, mitochondrial, and neuronal plasma membranes, with levels being the lowest in mitochondrial membranes (one‐way ANOVA with Tukey HSD, P<0.05). Both followed a similar distribution pattern in the prefrontal cortex and striatum, but not cerebellum. In the prefrontal cortex, age adjusted lutein and DHA levels were inversely associated in myelin membranes only (r = −0.73, P<0.03), while in the striatum, lutein and DHA were positively related in nuclear (r = 0.77, P<0.02) and mitochondrial membranes (r = 0.88, P<0.004). Co‐localization of lutein and DHA in some membranes and regions, but not others, may be indicative of varied, and specific, functions of lutein in different brain regions. Results from this study provide the first steps toward understanding lutein's mechanism of action in the brain and its relationship to DHA.

Support or Funding Information

This work was supported by grants from Abbott Nutrition through the Center for Nutrition, Learning, and Memory at the University of Illinois, DSM Nutritional Products, and USDA (58‐1950‐4‐003), and NIH grant P51OD011092 to the Oregon National Primate Research Center
Identification of methylated avenanthramides in human plasma
Authors: Walsh Jason , Haddock Jordan , McKay Diane L. , Collins F. William , Blumberg Jeffrey B. , Chen C‐Y. Oliver
Published: June 2021

Avenanthramides (AVs) are phytochemicals unique to oats consisting of an anthranilic acid and hydroxycinnamic acid linked by a pseudo‐peptide bond. We have demonstrated AV bioavailability to be low in hamsters and humans, suggesting they may be metabolized by phase II enzymes to facilitate their rapid excretion. Thus, we sought to identify the presence of phase II metabolites of 6 dominant AV isomers (A, B, C, O, P, and Q). AV‐A, ‐B, and ‐C differ in the moiety at position 3 (A: ‐H; B: ‐CH3O; and C: ‐OH) of the cinnamic acid ring, and AV‐O, ‐P, and ‐Q correspond to A, B, and C in terms of position 3 but differ in the length of the pseudo‐peptide linkage. We conducted a placebo‐controlled, crossover study in 10 healthy adults (60.4 y, BMI = 25.3). Blood was collected at 0, 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 10, and 24 h after consumption of a muffin made with either 20 g AV‐enriched oat bran (containing 46.2 mg total AVs) or regular oat bran. After removal of lipids with hexane, AV phase II metabolites in the defatted plasma were extracted twice with ethyl acetate, dried under N2, and reconstituted in 55% methanol for analysis on an Agilent UPLC‐QToF‐MS equipped with an Agilent Zorbax Extend C‐18 RR HT column (2.1 × 50 mm, 1.8 μm). Utilizing the MassHunter Qualitative Analysis software, we identified with a confidence score ≥80 for aglycones AV‐O and ‐A, and ≥90 for methylated AV‐O. Their detection is consistent with plasma AV results obtained after the removal of the glucuronide and sulfate conjugates that AV‐O and ‐A were the most abundant isomers. AV‐A was detected at fewer time points than AV‐O probably due to its much lower circulating concentrations. AV‐A had a maximum concentration (Cmax) of 2.2 ± 1.6 ng/mL with the time to reach Cmax (Tmax) at 1.9 ± 0.8 h. The Cmax for AV‐O was 6.4 ± 3.9 ng/mL and the Tmax was 2.6 ± 0.8 h, as well as 14.0 ± 8.2 ng/mL AV‐O equivalents and 1.9 ± 0.7 h for methylated AV‐O. Though AVs are extensively transformed to phase II metabolites, our analyses reveal the presence of AV‐O and ‐A aglycones in the circulation. Ours is the first report of a methylated AV metabolite following acute AV consumption. Future studies are warranted to explore the potential bioactivity of methylated AVs.

Support or Funding Information

Supported by USDA and PepsiCo
The Heat Shock Protein 70 is a Novel Target for Nobiletin in Human Colon Cancer Cells
Authors: Gao Zili , Zheng Jinkai , Wu Xian , Dimova Kalina , Scordilis Stylianos , Xiao Hang
Published: June 2021

Nobiletin is a unique flavonoid mainly found in citrus fruits, and has been reported to inhibit colon carcinogenesis in multiple rodent models. However, the direct molecular targets of nobiletin are unknown. Heat shock protein 70 (HSP70) contributes to cancer cell survival and resistance to chemotherapies, thereby inhibition of HSP70 is a promising strategy in cancer chemoprevention. Using affinity chromatography, we demonstrated that nobiletin bound to HSP70 at its ATP‐binding domains in human colon cancer cells and specifically inhibited its ATPase activity. Down regulation of HSP70 by siRNAs significantly increased cancer cells’ sensitivity to nobiletin treatments, which were evidenced by increased apoptosis and decreased colony formation capacity of cancer cells. The association between HSP70 and HSP90 is critical for the stability of their client proteins, such as EGFR, AKT, and STAT3, which contributes to carcinogenesis. We found that nobiletin disrupted the association between HSP70 and HSP90, and combined treatment with nobiletin and HSP90 inhibitors promoted the degradation of those client proteins. Moreover, combined treatment with nobiletin and HSP90 inhibitors resulted in enhanced inhibition on cancer cell growth by inducing apoptosis and cell cycle arrest. Most interestingly, our results also demonstrated that the major colonic metabolites of nobiletin (generated in the colon of mice fed with nobiletin) showed similar inhibitory effects against HSP70‐mediated signaling pathways. Overall, our results demonstrated, for the first time, that HSP70 is a promising target of nobiletin and its colonic metabolites in inhibiting human colon cancer cell growth, which warrants further investigation on their role in colon cancer chemoprevention.

Support or Funding Information

This study was supported by funding from NIH, AICR and USDA.
Dietary quercetin inhibits methylglyoxal‐induced advanced glycation end products formation in mice
Authors: Zhao Yantao , Wang Pei , Chen Huadong , Sang Shengmin
Published: June 2021

Increasing evidence has identified the formation of advanced glycation end products (AGEs) as a major pathogenic link between hyperglycemia and diabetes‐related complications. As the precursor of AGEs, methylglyoxal (MGO) is observed at relative higher plasma levels (2–6 fold) in diabetic patients than in healthy subjects and are also found in many food products, beverages and cigarette smoke. Chronic intake of exogenous MGO has been demonstrated as one of the cause factors for the development of diabetes. Therefore, decreasing the levels of MGO will be an effective approach to reduce the formation of AGEs and the development of diabetic complications. In this study, we investigated whether long‐term treatment of MGO in drinking water can cause protein glycation in mice and whether dietary flavonoids, such as quercetin, can prevent the formation of AGEs via trapping MGO. Our results indicate that chronic MGO administration (0.06% in drinking water for 20 weeks) significantly elevates the levels of MGO and AGEs in mouse plasma, liver and kidney, and cause liver injury. Dietary quercetin treatment (0.067% and 0.2% in diet) ameliorates MGO‐induced liver injury and prevents the formation of AGEs at least in Kidney. Further mechanistic studies demonstrate that both quercein and its major metabolite isorhamnetin could trap MGO in mice to form mono‐ and di‐MGO adducts. In addition, quercetin could increase glyoxalase I and II expression and GSH/GSSG ratio to promote the detoxification of MGO.

Support or Funding Information

USDA‐AFRI grant 2012‐67017‐30175 to S. Sang
Using Synthetic Biology methods to construct a rapid and efficient estrogen biosensor
Authors: Lynott Michaela , Huttelmaier Stefanie , Tobiason Deborah , Canfield Jennifer
Published: June 2021

Synthetic Biology demonstrates the integral relationship between biology, chemistry, mathematics and computer science. The field provides innovative approaches to a wide range of applications, such as bioremediation, sustainable energy production and biomedical therapies. Synthetic biology involves construction of genetic circuits when DNA sequences are modified to include standard restriction enzyme sites making the DNA sequences interchangeable and allowing for construction of a variety of circuits. New tools and devices are constantly needed to enhance the already extensive list of BioBricks housed at the Registry of Standard Biological Parts. As proof of concept we constructed a new BioBricks based on the toluene sensor built by Stiner and Haverson (AEM, 2002) in Pseudomonas. Toluene is an environmental contaminant that is the byproduct of oil contamination. Biosensors generated from BioBrick parts yield more affordable, transportable, and faster methods of pollutant detection. The tbuT cassette from Stiner and Haverson's work was digested with XbaI and SpeI sites then ligated with the GFP reporter gene and cloned into iGEM BioBrick vectors in order to create a biosensor in Escherichia coli. These BioBricks can be readily used with a variety of reporter genes to create new versions of the biosensor. We expanded our biosensor construction to create a dual functional estrogen sensitive BioBrick. The presence of estrogenic compounds (endocrine‐disruptors, EDCs) in the water supply raises concerns about human and aquatic health. Current methods for detecting estrogen contamination require expensive, time‐consuming techniques such as liquid chromatography‐mass spectrometry and high performance liquid chromatography. Previously reported estrogen biosensors required multiple cloning and transformation steps for successful detection in bacteria. Our estrogen responsive plasmid contains parts that allow for both the constitutive expression of the estrogen receptor followed by an estrogen response element toggled to a reporter gene in a single vector. When the estrogen response element is activated the reporter gene, red fluorescent protein, will produce a color change in E.coli. We will present data demonstrating the efficiency of this dual‐functional biosensor and it effectiveness for estrogenic compounds in contaminated water.

Support or Funding Information

NSF grant #NSF‐GPG‐1444406, GPG: Research Collaboration: REU Pilot: Synthetic Biology Boot camp
Structural and Biochemical Characterization of AidC, a Quorum‐Quenching Lactonase With Atypical Selectivity
Authors: Mascarenhas Romila Nina
Published: June 2021

Quorum‐quenching catalysts are of interest for potential application as biochemical tools for interrogating interbacterial communication pathways, as antibiofouling agents, and as anti‐infective agents in plants and animals. Herein, the structure and function of AidC, an N‐acyl‐l‐homoserine lactone (AHL) lactonase from Chryseobacterium, is characterized. Steady‐state kinetics show that zinc‐supplemented AidC is the most efficient wild‐type quorum‐quenching enzymes characterized to date, with a kcat/KM value of approximately 2 × 106 M−1 s−1 for N‐heptanoyl‐l‐homoserine lactone. The enzyme has stricter substrate selectivity and significantly lower KM values (ca. 50 μM for preferred substrates) compared to those of typical AHL lactonases (ca. >1 mM). X‐ray crystal structures of AidC alone and with the product N‐hexanoyl‐l‐homoserine were determined at resolutions of 1.09 and 1.67 Å, respectively. Each structure displays as a dimer, and dimeric oligiomerization was also observed in solution by size‐exclusion chromatography coupled with multiangle light scattering. The structures reveal two atypical features as compared to previously characterized AHL lactonases: a “kinked” α‐helix that forms part of a closed binding pocket that provides affinity and enforces selectivity for AHL substrates and an active‐site His substitution that is usually found in a homologous family of phosphodiesterases. Mutations on this His substitution are being studied along with other suspected catalytic residues. Implications of the catalytic mechanism of AHL lactonases will be discussed based on these data and prior knowledge of other AHL lactonases.

Support or Funding Information

National Science Foundation, Grant No. CHE‐1308672
Dynamic Stiffness Reveals New Cardiac Phenotypes in Patient‐Derived iPSCs
Authors: Engler Adam J.
Published: June 2021

After nearly a decade of recognition that extracellular matrix (ECM) properties can influence cell behavior to similar degree as growth factors, in particular ECM composition, topography, porosity, and stiffness, biologists have come to recognize its importance. However matrix is highly dynamic, changing how much of it is secreted and assembled during development and disease. Most synthetic ECM mimics made initially to study this phenomenon were static but there is growing interest in making matrices that have tunable properties with time. To accomplish this, my lab has created hyaluronic acid (HA)‐based materials that crosslink themselves spontaneously or via UV‐sensitive reactions to provide slow or “on‐demand” changes in stiffness. By knowing the dynamics of matrix assembly during heart development as well as heart remodeling post‐heart attack, we have used these HA materials to model how the heart tube stiffens or the onset of fibrosis (i.e. “heart attack‐in‐a‐dish”), respectively, to understand how temporal changes in stiffness better instruct differentiation and function. Using an embryonic heart model, we have found that developmentally appropriate stiffening can drive maturation and sarcomere assembly in pre‐cardiac mesoderm. Conversely using patient‐derived induced pluripotent stem cells (iPSCs) in HA that models a “heart attack‐in‐a‐dish,” we have identified new cardiac phenotypes in diseased cardiomyocytes that were previous masked by other conditions in patients. We have also used the materials to study cardiac disease mechanisms, since often phenotypes do not appear until cells are stressed by the “heart attack‐in‐a‐dish” conditions. Based on these exciting results, we believe that any in vitro culture system should employ dynamic materials that change as the niche does in vivo.

Support or Funding Information

NIA/NIH, NHLBI/NIH, NSF, and AHA
Using Skin Carotenoids to Assess Potential Dietary Changes After One Academic Year in the Shaping Healthy Choices Program
Authors: Nguyen Lori M , Scherr Rachel E , Dharmar Madan , Ermakov Igor V , Gellermann Werner , Jahns Lisa , Linnell Jessica D , Keen Carl L , Miyamoto Sheridan , Steinberg Francene M , Young Heather M , Zidenberg‐Cherr Sheri
Published: June 2021

Reported dietary intake is often used in community interventions to assess intake of fruits and vegetables (F/V); however, dietary assessment methods are inaccurate, and time and labor intensive. Skin carotenoids are a potential biomarker to assess F/V intake given that carotenoids are predominately found in F/V and their concentration in the skin can reflect dietary intakes of F/V. The Resonance Raman Spectroscopy (RRS) method is a quick and validated method to assess skin carotenoids. The objective of this study was to determine whether skin carotenoids measured by RRS can be used to confirm changes in dietary intake of F/V in 4th‐grade students participating in the Shaping Healthy Choices Program (SHCP). The SHCP is a multi‐component nutrition intervention and one of its aims is to increase F/V intake. Dietary intake was assessed using the Block Food Frequency Questionnaire in a subset of students (n=30) and skin carotenoids were measured using RRS (n=82) before and after the SHCP intervention. Pre‐post changes in F/V intake measured by each method were tested using Student's t‐tests. After 9 months, reported intake of carotenoids decreased by 19% (1469mcg, P=0.05) and skin carotenoids decreased by 9% (2882 RRS intensity units, P<0.001). Change in reported intake correlated with change in skin carotenoids (r=0.43, P=0.02). While the reported decrease in F/V intake in this population was unanticipated given that the intervention aimed to increase intake, the RRS measurements confirmed this change. In conclusion, optically measured skin carotenoids can be used to help evaluate changes after 9 months of F/V intake in 4th‐grade students.

Support or Funding Information

Funding was provided by UCANR competitive grant #11‐1018, USDA 2011‐38420‐20082, and USDA NIFA, Hatch project 221082.
Vitamin B12 and Folate Status in Pregnant Adolescents and Their Infants
Authors: Finkelstein Julia L. , Guillet Ronnie , Pressman Eva K. , Kent Tera R. , O'Brien Kimberly O.
Published: June 2021

Objective

To determine the prevalence of vitamin B12 deficiency and examine the associations between maternal and infant vitamin B12 and folate status in a cohort of healthy pregnant adolescents.

Design

Serum vitamin B12 and folate concentrations were measured in pregnant adolescents at mid‐gestation, delivery, and in cord blood. Linear and binomial regression models were used to examine the associations between maternal and infant vitamin B12 and folate status.

Results

Serum vitamin B12 concentrations decreased significantly during pregnancy (p<0.0001) resulting in an increased prevalence of vitamin B12 deficiency (<148 pmol/L) from mid‐gestation (1.6%) to delivery (15.3%). At delivery, an additional 46.6% of mothers were vitamin B12 insufficient (<200 pmol/L). Maternal vitamin B12 concentrations (p<0.001) and vitamin B12 deficiency (p<0.001) at delivery were associated with infant B12 concentrations, with 1% of infants being vitamin B12 deficient at birth. Similarly, maternal folate concentrations at delivery (p<0.001) were associated with infant folate concentrations.

Conclusions

Maternal vitamin B12 and folate status at delivery predicted infant vitamin B12 and folate status in healthy pregnant adolescents.

Support or Funding Information

Supported by grants from the United States Department of Agriculture (USDA): USDA 2005‐35200‐15218 and USDA 2010‐34324‐20769; and the Division of Nutritional Sciences, Cornell University