bluuebunny/crossref_metadata_2025 huggingface dataset:
The role of gut microbiota on the metabolism of black tea theaflavins
Authors: Zhang Shuwei , Ohland Christina L , Jobin Christian , Sang Shengmin
Published: November 2023

The main bioactive polyphenols in black tea are theaflavins, including theaflavin (TF), theaflavin‐3‐gallate (TF3G), theaflavin‐3¢‐gallate (TF3¢G), and theaflavin‐3,3¢‐digallate (TFDG). Theaflavins have been reported as anti‐inflammatory and cancer preventive agents in different in vitro and in vivo models. Because of the poor systemic bioavailability of theaflavins, it is still unclear how these compounds can exert their biological functions. Studies have shown that higher molecular weight polyphenols are metabolized by the microbiota and their metabolites may play an important role in chronic disease prevention. The objective of this study is to identify the microbial metabolites of theaflavins in mice and in humans. Purified TF and TFDG were oral gavaged to specific pathogen free (SPF) mice, germ free (GF) mice, and incubated with human fecal slurries in vitro. Microbial bioconversion was monitored using liquid chromatography/mass spectrometry (LC/MS) by analyzing the MSn (n = 1–3) spectra. Our results indicated that TFDG can be metabolized by gut microbiota to generate gallic acid, pyrogallol, TF, TF3G, and TF3'G, and TF can be further broke down to small molecular metabolites by gut microbiota. Furthermore, we used selective culturing techniques to probe which bacterial groups are responsible for theaflavins metabolism in vitro. Fecal bacteria from SPF‐born 129SvEv mice were anaerobically cultured on blood agar (non‐selective agar), MacConkey agar (selective for gram‐negatives; G−) and Columbia colistin and nalidixic acid agar (gram‐positives; G+). The cultures were then anaerobically incubated in fermentation media containing theaflavins, and the resulting metabolites were analyzed by LC/MS. Lactobacillus plantarum and Escherichia coli NC101 were similarly assessed for theaflavins fermentation abilities. Our results revealed that the G+ bacteria (including L. plantarum on its own) instead of G− bacteria (including E. coli NC101 on its own) were able to produce these metabolites.

Support or Funding Information

This work was supported by NIH R01 grant AT008623.
Comparison of Methods for Assessing Body Composition in Women
Authors: De Oliveira Mariane Helen , Silva Josilene Cheliga Ferreira , Ferreira Rosemeire Cheliga
Published: November 2023

Overweight has increased significantly in women. Obesity has shown associated with several disorders such as diabetes, cardiovascular disease and cancers. The purpose of this study was to evaluate the body composition of women through the anthropometry and electrical bio impedance methods. It was a cross‐sectional study with 50 not pregnant women with the average age of 27.58 ± 13.76 years (range 22–35 years). It was evaluated the Body Mass Index (BMI), Waist Circumference (WC), Waist‐to‐Hip Ratio (WHR), body density through the formulas of Durnin and Womersley (1974), Jackson, Pollock and Ward (1980), Petroski (1995), Pollock, Schimidt and Jackson (1980), and the body fat percentage was obtained through the bio impedance analyses (BIO), Body Adiposity Index (BAI), and formula of Siri (1961). The average values obtained were: weight: 68.5 ± 14.23 Kg (range 45.2–104.5Kg); height: 1.61 ± 0.07 m (range 1.45–1.75m); WC: 76.67 ± 8.8 cm (range 57.17–96.5 cm); WHR: 0.75 ± 0.05 (range 0.64–0.88); BMI: 26.38 ± 4.72 Kg/m2 (range 17.4–38.5 Kg/m2). The body fat percentages obtained were by: Durnin and Womersley (1974): 42.67 ± 3.72% (range 3.92–50.12%); Jackson Pollock and Ward (1980): 37.90 ± 5.89% (range 23.27–46.88%); Petroski (1995): 35.52 ± 3.72% (range 24.75–41.65%); Pollock, Schimidt and Jackson (1980): 40.28 ± 5.08% (range 25.44–48.24%); Pollock, Schimidt and Jackson (1980): 37.93% ± 4.62 (range 23.43–43.68); BAI: 32.11 ± 4.72% (range 21.93–44.53) and BIO: 31.87 ± 9.39% (range 3–44.4). The CVD risks were 32% and 72% for WC and WHR methods, respectively. According to BMI 60% has overweight, while that the excess of body fat affects 54% and 66% through the BAI and BIO methods, respectively. It was observed that the BAI was the method with the closest value compared to the BIO. BMI, BAI and skinfold methods of Petroski (1995) and Jackson Pollock and Ward (1980) were the most effective to assess the body composition of the sample. WHR proved to be more accurate to evaluate the CVD risks than isolated WC. It is necessary more studies to validate the use of BAI to access the body composition of the Brazilian population.

Support or Funding Information

This research was supported by the Clinical Nutrition Department of the Faculdades Integradas Coração de Jesus.
Egg White Protein Meals Induce Greater Satiety and Plasma Amino Acids Compared to Wheat Gluten Protein Meals
Authors: Du Kristy , Markus Edward , Fecych Mariel , Beverly J. Lee , Rhodes Justin S , Dailey Megan J
Published: November 2023

While dietary protein is known to induce greater satiety than fats and carbohydrates, the extent to which the source of protein matters and the mechanisms involved are less certain. This study examined the effect of the level and source of protein on subsequent food intake, metabolism, and changes in plasma amino acids in adult Sprague‐Dawley rats. Rats were entrained to a meal‐feeding schedule consisting of a 30‐minute treatment meal, equivalent to 10–20% of average daily intake, one hour into the dark phase followed by ad libitum access to a control diet for 5.5 hours later in the dark phase. Treatments were 1) 20% wheat gluten, 2) 35% wheat gluten, 3) 20% egg white, and 4) 35% egg white and provided in a randomized crossover design. Energy expenditure and food intake patterns were measured using indirect calorimetry housing system. Rats provided meals containing egg white protein had decreased food intake at the subsequent meal compared to wheat gluten fed rats, regardless of protein level (P<0.005). While energy expenditure did not differ among treatments, respiratory exchange ratio following ingestion of the 35% egg white protein meal was lower than the other treatment meals for several hours following ingestion (P<0.001). In a separate cohort of rats, blood plasma was collected at 30 minute intervals for 2 hours following ingestion of the treatment meals. Analysis of plasma amino acid concentrations revealed greater increases in measured amino acids following ingestion of meals containing egg white protein. Specifically, concentrations of valine and lysine were the largest contributors to the difference observed in plasma amino acids. Overall, these results suggest protein‐induced satiety depends on the protein source. Egg white protein caused greater satiety than wheat gluten protein, corresponding to greater postprandial increases of plasma amino acids. These results collectively highlight the importance of the consideration of protein sources as it relates to controlling appetite.

Support or Funding Information

DK082609 awarded to JLB
The Effects of Acute Freeze‐Dried Mango Consumption with a High‐Fat Meal on Post‐Prandial Responses in Healthy Young Adult Males
Authors: O'Hara Crystal , Ojo Babjide , Simenson Ashley , Hermann Janice , Payton Mark , Smith Brenda , Lucas Edralin
Published: November 2023

Changes in post‐prandial oxidative stress, inflammation, hyperglycemia and hyperlipidemia, particularly after a high fat meal, have been implicated in the development of cardiovascular disease (CVD). An individual spends approximately 16 hours a day in the postprandial phase, and attenuating the acute responses that occur during this state could be an effective strategy to reducing these risk factors for CVD. Fruits and vegetables have been shown to have numerous health benefits including reducing oxidative stress and inflammation due to the many phytochemicals they contain. One such fruit is mango which contains significant amounts of beta carotene and vitamin C as well as many other nutrients and phenolic compounds such as mangiferin. The aim of this study is to determine if acute mango pulp consumption together with a high fat meal challenge will modulate postprandial responses in healthy young adult males.

Methods

In a cross‐over study design, twenty‐five healthy young adult males (18–25 years old) were asked to consume a typical American breakfast (45% fat) with or without the consumption of freeze‐dried mango pulp (50g given as shake). Blood samples were taken at baseline, 1, 2, and 4 hours after the meal. Anthropometrics, dietary and physical activity, and clinical parameters were assessed.

Results

There were no significant differences in antioxidant enzymes (GPx, CAT), inflammatory markers (TNF‐α or CRP), lipid parameters (cholesterol, LDL, HDL, TG, or NEFA) at all time points with acute mango consumption. One hour after the meal with mango, plasma glucose (p=0.04) and the antioxidant enzyme SOD (P=0.041) were significantly lower. IL‐6 tended to be lower (p=0.07) four hours after the meal with mango shake. There were no significant differences in area under the curve for any of the assessed parameters.

Conclusion

Acute mango consumption had modest effects on post‐prandial responses.

Support or Funding Information

Supported by OSU College of Human Sciences and a grant from the National Mango Board
The Provision of Ultra‐Processed Foods and their Contribution to Sodium Availability in Australian Long Day Care Centres
Authors: O'Halloran Siobhan A , Lacy Kathleen E , Woods Julie , Grimes Carley A , Campbell Karen J , Nowson Caryl A
Published: November 2023

Objectives

To categorise and assess all food, beverages and ingredients provided over one week at Australian Long Day Care (LDC) centres according to four levels of food processing and to assess the contribution of sodium from each level of processing.

Design

Cross‐sectional

Setting

Menus for lunch, morning and afternoon snacks were collected from LDC centres. The level of food processing of all food, beverage and ingredients were assessed utilising a four level processed food classification system: Minimally Processed (MP), Processed Culinary Ingredients (PCI), Processed (P) and Ultra Processed (ULP).

Results

A total of 35 menus (lunch n = 35, snacks n = 70) provided to 1–5 year old children were collected from seven LDC centres. The proportions of foodstuffs classified as MP, PCI, P and ULP: 54%, 10%, 15% and 21%, respectively. All lunches were classified as MP. Ultra‐processed foods accounted for 6% of morning snacks; 41% of afternoon snacks. The average amount of sodium provided per child/day across all centres: 633 (151) (SD) mg/d. ULP foods provided the most sodium (40%), followed by P foods (35%), MP foods (23%) and PCI (2%).

Conclusion

On average, centres provided foods resulting in a total daily sodium content 40–50% less than the recommended Upper Level (UL) of intake for sodium for this age group. The extensive use of MP foods, resulted in provision of low salt foods to this group of pre‐school children, which is likely to assist in maintaining their total daily sodium intake below the UL for dietary sodium.

Support or Funding Information

Nothing to declare
Synthesis of a novel non‐diuretic, brain‐penetrating, ethacrynic acid analog and demonstration of its potent efficacy in orthotopic glioblastoma (GBM) models
Authors: Madala Hanumantha Rao , Punganuru Surendra Reddy , KALKUNTE SRIVENUGOPAL
Published: November 2023

The incidence of pediatric and adult brain tumors has continued to rise in the USA and the alkylating agent temozolomide has remained the sole choice in the chemotherapy of these lethal malignancies. Therefore, there is a very urgent need to design new, more effective brain‐penetrating drugs that can significantly advance the survival brain tumor patients. We are highly interested in exploiting the elevated oxidative stress present in gliomas and have synthesized a hydrophobic, non‐diuretic analog of ethacrynic acid (EA) called KSS72 by removing the carboxylate side chain. KSS72 was selectively cytotoxic to cancer cells and pharmacokinetics following intravenous or oral administrations in mice showed its excellent penetrance through the blood‐brain‐barrier, accumulating at levels equivalent to (TMZ) in the brain. In vitro assays measuring protein carbonyl content, GSH content, ROS generation, GSTpi enzyme activity and others showed that KSS72 triggers a redox imbalance by inhibiting GSTpi and by lowering the antioxidant (GSH) and reducing equivalent (NADPH) levels, leading to a significant elevation of ROS levels. We also showed the upregulation of endoplasmic reticulum (ER) stress‐responsive proteins, activation of MAPK, autophagy and apoptotic pathways by KSS72 in several cell lines. In view of its excellent brain penetrance and multiple cytocidal events mediated by ROS, we tested the antitumor efficacy of KSS72 in human GBM cell lines and intracranial GBM xenografts. SF‐188 human GBM cells expressing firefly luciferase were injected into the brain just left of bregma for the development of orthotopic GBM in nude mice. These mice were given 25 mg/kg/day of KSS72 intraperitoneally for 2 weeks. The animals when imaged by IVIS after luciferin injections showed a complete lack of intracranial tumors in all KSS72 administered animals. H&E staining of mouse brain sections confirmed the total elimination of GBM by KSS72. KSS72 did not exert any toxicity on host tissues and serum ALT and AST levels were not altered. In summary, we conclude that KSS72 acting through multiple pathways of oxidative stress is a hugely promising non‐toxic anti‐glioma drug with potential to enter clinical trials.

Support or Funding Information

CPRIT grant RP130266 to KSS.
Localization of Scleraxis in Dermal and Keloid Fibroblasts
Authors: Johnson Charles , Nillas Andrea , Reaves Titus A.
Published: November 2023

Scleraxis is a transcription factor in the basic helix‐loop‐helix family that regulates the development of human embryonic cells into specialized tissue and was originally determined to be involved in tendon and bone formation. More recent studies have shown that scleraxis displays a more diverse presence in both normal and diseased tissues. In particular, scleraxis has been implicated in keloid disease (KD). The principal dysregulated cell in KD is the fibroblast. Fibroblasts are mesenchymal cells that play an essential role in tissue development and tissue repair. In the skin, there are papillary and reticular fibroblasts. While not completely known, it is believed that following an insult, reticular fibroblasts develop a hyper‐proliferative phenotype and become the keloid fibroblast. Despite this information, little is known of the molecular events that lead to KD. Therefore, we investigated the localization of scleraxis in the skin and fibroblasts and how scleraxis may affect fibroblast activation. Immunohistochemistry shows that scleraxis is localized in the keloid skin in the area of the melanocyte, papillary and the reticular areas. Western blot studies show that scleraxis is present in both keloid skin and keloid fibroblasts evenly distributed). Interestingly, using detergent lysates we show that scleraxis is also present in dermal fibroblasts. Scratch assays also show that scleraxis may play a role in the fibroblast migration. Specifically, when the N‐terminal region of a scleraxis peptide was added to cultures of fibroblasts and compared to a control, closures of the scratch were 50% slower when scleraxis peptide was added. Additional results reveal that scleraxis may be a secreted protein. Taken together these results suggest that scleraxis is present in both normal dermal and keloid fibroblasts, and may play a role in the activation of such fibroblasts.

Support or Funding Information

National Science Foundation R‐II
Neuroanatomical Analysis of a Conditional Knockin Mutant PHOX2B Mouse Model
Authors: Liu Jillian , Czeisler Catherine , Fair Summer , Goksel Behiye , Goksel Mustafa , Otero Jose
Published: November 2023

Background

Central Congenital Hypoventilation Syndrome (CCHS) is a rare disorder characterized by autonomic dysfunction, including abnormal respiration. Symptoms of CCHS include the inability to establish a regular respiratory rhythm, inadequate responses to hypoxemia and hypercapnia, heart rate abnormalities, and impaired bowel function. Mutations in paired‐like homeobox 2b (PHOX2B) are known to be causative for CCHS. We previously demonstrated that mice harboring an eight‐nucleotide deletion in PHOX2B (d8‐PHOX2B) displayed diffuse hindbrain pathology and perinatal lethality due to lack of spontaneous respiration. In this study, we are further exploring which brainstem circuits are required at birth for proper respiratory function and whether specific circuits are lost or insufficiently matured in mice expressing d8‐PHOX2B.

Methods

We are crossing several Cre driver mice with d8‐PHOX2B mice to selectively express d8‐PHOX2B in hindbrain neural nuclei known to be affected by mutant PHOX2B expression. Histological examination of brainstems from these mice along with unbiased quantification will allow us to determine how the morphology and number of cells within these neural populations is altered.

Preliminary results

Atoh1‐cre; d8‐PHOX2B mice were generated and assessed for perinatal viability, as Atoh1 is a transcription factor known to be involved in the development of medullary respiratory centers. At birth Atoh1‐cre; d8‐PHOX2B pups appeared healthy and displayed spontaneous respiration. Histological examination of hindbrains from these pups revealed no neuropathology, with evident intact locus coeruleus, facial nucleus, and retrotrapezoid nucleus. These preliminary results suggest that the expression of Phox2b in the Atoh1 lineage is not required for normal hindbrain development and respiration at birth.

Support or Funding Information

1R01HL132355‐01A1
Enteroaggregative Escherichia coli delocalized b‐catenin adherens junction in ileum and colon enterocytes in an infection mouse model with an disturbed microbiota
Authors: García Nadia Elisa Moran , Lopez‐Saucedo Catalina , Galindo‐Gómez Silvia , Tsutsumi Victor , Felipe‐Lopez Alfonso , Schnoor Michael , Nataro James P. , Estrada‐Garcia Teresa
Published: November 2023

Objectives: to develop an undisturbed microbiota mouse model of enteroaggregative E. coli (EAEC) infection, a diarrheagenic E. coli pathogroup associated with both pediatric and traveler's diarrhea illness and to evaluate in situ the role of AAF/II fimbria, which is responsible for the characteristic aggregative phenotype of this pathogroup. Six week old C57BL/6 mice, without antibiotic treatment, were orally inoculated with different concentrations of 042 EAEC prototype strain. For the 042 AAF/II fimbria experiments, one group of mice was inoculated with 042 wild type strain and another group with the adherence fimbria II 042 mutant (ΔAAF/II) strain. Control mice were orally given 100 μL 0.8% saline solution. Paraffin section of colon and Ileum were analyzed by Hematoxylin & Eosin and Periodic Acid‐Schiff (PAS) staining and by immunofluorescence for ββ‐catenin and ZO‐1 distribution. The optimal EAEC infectious dose for EAEC‐mouse model was 5×109 042 UFC/100 μL, since none of the animals died, remained colonized for 50 days and ileum and colon sections of 7 days post‐infected mice had significantly more goblet cells and increased mucus production; EAEC illness is characterized by diarrhea with mucus. In addition, Ileum villi of infected mice were shorter with wider bases and some edema areas were observed; indicating an infection process. In both ileum and colon sections of 4 and 7 days post‐infected mice, ββ‐catenin was partial delocalized from its common enterocyte basolateral localization, increasing its expression in the cytoplasm and appearing along the apical enterocyte surface, whereas ZO‐1 localization remained unaltered. In contrast, ββ‐catenin was not delocalized in the ileum enterocytes of 4‐days ΔAAF/II EAEC 042 post infected mice, although was delocalized in the colon enterocytes. Suggesting that the AAF/II fimbria plays a role in ββ‐catenin delocalization in ileum enterocyte but not in colon cells. To the best of our knowledge, for the first time we have developed a mouse model of EAEC infection with an undisturbed microbiota, revealed that β‐catenin is delocalized after EAEC infection and relocalized to the apical surface of the enterocytes and that AAF/II fimbria plays a role in β‐catenin delocalization in ileum enterocytes. Overall our results have shown that this new model will be an excellent tool to unveil early EAEC infection events in vivo and in situ.

Support or Funding Information
Aging‐related Changes in Gut Microbiome Mediate Septic Kidney Injury
Authors: Colbert James F , Ford Joshay A , Dailey Kyrie L , Frank Daniel N , Faubel Sarah , Schmidt Eric P
Published: November 2023

BACKGROUND

Sepsis, a dysregulated systemic response to infection, is a major cause of morbidity and mortality worldwide. Older adults are particularly vulnerable to this syndrome, as evidenced by higher sepsis incidence and mortality. It is well established that the development of organ failure, specifically acute kidney injury (AKI), is a strong predictor of mortality during sepsis and occurs more frequently in the aging population. Despite this association, the mechanisms underlying the development of septic AKI remain undetermined. Extensive prior research attempting to interrupt or reverse septic organ injury has yielded no successful therapies in humans. Given these past failures, it is crucial to investigate novel concepts driving septic AKI and resulting mortality in the aging population.

METHODS

We used two distinct models of experimental sepsis to induce kidney injury in young (8–12 weeks) and aged (20–24 months) C57BL/6 mice. One model (cecal ligation and puncture, CLP) induces sepsis via leakage of the host cecal microbiome into the peritoneal space. A second model (fecal slurry) allows for direct introduction of different microbiota (isolated from the stool of young vs. aged mice) into the peritoneum. We collected plasma, urine, and kidneys 24 hours after the onset of experimental sepsis. Sham mice and intraperitoneal saline injection mice served as contemporaneous controls in both age groups. We measured kidney injury by markers of glomerular filtration (Blood Urea Nitrogen, BUN), tubular injury (kidney homogenate neutrophil gelatinase‐associated lipocalin (NGAL) by qRT‐PCR), and inflammation (kidney homogenate interleukin‐6 (IL‐6) by qRT‐PCR).

RESULTS

Aged mice demonstrate worsened septic AKI compared to young mice after experimental sepsis induced by CLP. Kidney injury in aged mice demonstrated a predominance of glomerular dysfunction (as measured by BUN), with less tubular injury (NGAL) or inflammatory changes (IL‐6). Additionally, septic AKI (as measured by BUN) was exaggerated in young mice exposed to the intraperitoneal injection of fecal slurry collected from aged mice, as compared to fecal slurry collected from young mice.

CONCLUSIONS

Our preliminary data indicate that sepsis associated AKI in aged mice is primarily a consequence of glomerular dysfunction. Strikingly, our observations suggest that the CLP‐induced glomerular dysfunction in aged mice is driven by increased virulence of the aged gut microbiome.

Support or Funding Information

JFC is supported by the Denver VA Geriatrics, Research, Educational, and Clinical Center (GRECC)

JFC was previously supported by National Institute of Health Grant T32AG000279
Inner ear of the cimolodontan multituberculate Meniscoessus robustus supports functional interpretation and a novel phylogenetic hypothesis
Authors: Weil Anne , Tomida Yukimitsu
Published: November 2023

The Multituberculata are an extinct branch of Mammalia with no living descendants. Among those multituberculate taxa with known crania, a large cavity within the petrosal, interpreted as housing a large vestibule, was initially thought to distinguish multituberculates from other mammals but has subsequently been shown to be limited, and perhaps phylogenetically informative, among the Cimolodonta.

We have confirmed, by μCT scanning a nearly complete skull of the Late Cretaceous North American species Meniscoessus robustus (NSM‐PV 20436), that Meniscoessus has a strikingly large vestibular cavity that is very similar to the vestibular cavity of Lambdopsalis. The smaller Lambdopsalis, occurring in Paleocene sediments of China and Mongolia, is distinctive. The vestibular cavity of Lambdopsalis is enormous relative to the size of the skull, creating a prominent bulge on the posterior and basicranial aspects. The presence and specific morphology of this structure, the presence of enlarged molars with crescentic cusps that wear rapidly to produce lophs oriented at 90° to masticatory direction, the shape of the frontal‐parietal suture, and additional characters of the braincase support an evolutionary history for the Asian Lambdopsalidae that has origins in the Late Cretaceous of North America, contrary to the direction of most hypothesized intercontinental migration.

There is no unambiguous boundary between the saccule and utricle of enlarged multituberculate vestibules; some authors have asserted the utricle is enlarged, while others find evidence for enlargement of the saccule. The ear of Meniscoessus supports an enlarged saccule. As in other multituberculates, the cochlea is curved; the specimen is not deformed so the degree of curvature may accurately record that of the living animal, and it does not differ greatly from those of other Cimolodonta. There is a distal expansion of the cochlea, but it is slight in comparison to some of those found in other taxa.

Support or Funding Information

This study was funded by: NSF‐DEB 0108294
The role of cardiac mesenchymal cells in patterning the SAN
Authors: Bressan Michael
Published: November 2023

Impulses generated by a multicellular, bioelectric, signaling center known as the sinoatrial node (SAN) stimulate the rhythmic beating of the heart. The SAN constitutes one of the most unique morphological structures in the heart, containing a network of electrochemically oscillating pacemaker cells encased in a heterogeneous connective tissue microenvironment. While the cellular composition of the mature SAN has been a point of interest for more then a century, the developmental ontogeny and biological processes that drive the integration and tissue‐level assembly of the cells present in the SAN have not been examined. Here we show that just following the differentiation of bona fide cardiac pacemaker cells, the myocardial wall surrounding these cells rapidly remodels. This results in the formation of a heterogeneous, cellular niche, composed of loosely packed pacemaker myocardium surrounded by non‐muscle mesenchymal cells. Using a combination of in vivo cell tracing and microsurgical techniques, our data demonstrate that a multipotent progenitor population, the proepicardium, is required for this remodeling to take place. Under normal conditions proepicardial‐derived cells rapidly and specifically invade the pacemaker region of the heart. Conversely, following proepicardial‐ablation, the pacemaker region fails to structurally remodel and displays severe dysfunction including decreased rhythmicity and disrupted electrical communication with the adjacent atrial myocardium. Importantly, these data demonstrate that SAN development requires not only the specification of a myocardial population capable of autonomous electrical impulse generation, but also the formation of a unique cellular microenvironment to surround and support these cells.

Support or Funding Information

Supported by R01 HL112268, K99HL 122360, and R00HL 122360
Opposing transcriptional forces underlie chronic disease caused by Toxoplasma gondii
Authors: White Michael , Hong Dong‐Pyo , Worth Danielle , Huang Sherri , Radke Josh , Sullivan William , Wilson Emma
Published: November 2023

Toxoplasma gondii infections continue to be a public health hazard for millions of individuals that contact this pathogen annually. More than 50 million individuals in the US are chronically infected with Toxoplasma gondii and thousands of healthy individuals develop eye disease due to this infection that can lead to permanent vision loss. The Centers for Disease Control and Prevention considers Toxoplasma one of the five most important neglected parasitic infections. Toxoplasma infections are life‐long due to the development of the bradyzoite‐tissue cyst. No current drug successfully treats or prevents the tissue cyst and this therapy failure leaves individuals who become infected vulnerable to disease relapse throughout their lifetimes. Despite the important clinical consequences of this developmental pathway, the molecular basis of the switch mechanisms that control formation of the tissue cyst is still poorly understood. Significant changes in gene expression are required to form the bradyzoite‐tissue cyst and ApiAP2 transcription factors are an important mechanism regulating this developmental transcriptome. ApiAP2 factors are a large family of proteins (67) in Toxoplasma that are distantly related to AP2 transcription factors of plants and not found in the human host. We will discuss our recent studies that have uncovered a complex ApiAP2 transcriptional network of repressors and activators competing at the interface of tachyzoite replication and early switching to regulate tissue cyst formation. We believe Toxoplasma may have evolved this complex transcriptional network to balance the competing demands of expanding the acute stage (tachyzoite) responsible for pathogenesis with the production of the dormant bradyzoite‐tissue cyst that is invisible to the immune system and required for transmission.

Support or Funding Information

National Institutes of Health, R01AI122760, R01AI09843, R56AI124682
Iron Deficiency and Depression in Female State Fair Attendees
Authors: Price Kathleen L , Abernathy Breann E , Dobbs Joannie C , Gallaher Daniel D
Published: November 2023

Iron deficiency persists as the most prevalent nutrient deficiency on the planet, and women of menstruating age are at high risk due to menstrual blood loss. Recent data suggests that iron deficiency in the absence of anemia can impact quality of life, and currently the prevalence of menstruating females with inadequate ferritin values in the US is high. One important quality of life factor that has been linked to iron deficiency is depression. Although an association between iron deficiency and depression has been supported by some observational studies, the findings are inconsistent. Thus, the objective of this study was to further examine the relationship between iron status and depression. This cross‐sectional study gathered survey data and blood samples from 190 pre‐menopausal female subjects at the Minnesota State Fair in August of 2015. Whole blood hemoglobin, hematocrit, serum ferritin and serum TIBC were determined and correlated to survey data detailing reported iron deficiency symptoms and their severity, including the PHQ9, a validated depression screen. 15% of subjects were anemic as defined by a hematocrit value under 38% or a hemoglobin value below 12 g/dL. Additionally, 73% had low ferritin status as defined by a value less than 20 mg/L. Overall, 18% of subjects reported moderate to severe depression as defined by the PHQ9. Although independent relationships between anemia, low ferritin values, or elevated TIBC values and depression were not seen, of the anemic subjects who also reported fatigue, 55% were moderately to severely depressed compared to 16% of anemic patients who did not report fatigue (p = 0.0065). Additionally, of the subjects with iron‐deficient values for both ferritin and TIBC who also reported fatigue, 47% were moderately to severely depressed compared to the 23% of subjects with iron‐deficient ferritin and TIBC values who did not report fatigue (p = 0.0084). Low iron status with reported fatigue, which we term functional iron deficiency, appears to be strongly associated with depression. Our results also suggest that biochemical indicators of iron status alone are inadequate to examine the relationship between iron status and depression, and that symptomatic indicators of iron deficiency should also be included.

Support or Funding Information

Supported by the Clinical and Translational Science Institute (CTSI) of the University of Minnesota
Genetic variation in the AMY1 gene is associated with dietary carbohydrate and starch intake in a young adult population
Authors: Sorkin Riva , Wolever Thomas , El‐Sohemy Ahmed
Published: November 2023

Background

Genetic variation contributes to individual differences in energy and nutrient intake and may be a contributing factor to the selection of certain foods and macronutrient preference. Salivary amylase is encoded by the AMY1 gene, which displays high copy number variation (CNV) and plays an important role in starch digestion. Research has found that AMY1 CNV is positively correlated with both salivary amylase concentration and activity and higher AMY1 copy numbers have been found in populations with high starch diets. Individual single nucleotide polymorphisms (SNPs) near the amylase genes have been found to correlate with AMY1 copy number within populations. The objective of this study was to determine whether common variants in the AMY1 gene are associated with habitual dietary intake.

Methods

Fasting blood samples were drawn from a total of 1,600 ethno‐culturally diverse participants aged 20–29 years from the Toronto Nutrigenomics and Health Study for genotyping of 9 SNPs associated with AMY1 copy number: rs4244372 (T/A), rs11577390 (C/T), rs1566154 (A/G), rs10881197(G/C), rs2132957 (A/G), rs11185098(G/A), rs1999478(C/A), rs1330403(A/G) and rs6696797(A/G). Dietary intake was assessed using a one‐month, 196‐item Toronto‐modified Willett food frequency questionnaire. An analysis of covariance adjusted for age, sex, ethnicity, BMI, and physical activity was used to determine the association between AMY1 genotypes and dietary intake.

Results

Among Caucasians (n = 620), carriers of the minor allele in rs10881197 had a significantly lower energy intake (1838 vs 2089 kcal/day, p = 0.005). Carriers of the minor allele in rs11185098 had significantly higher total carbohydrate (CHO) and starch intakes (273 vs 266 g CHO/day, p =0.03 and 122 vs 117g starch/day, p= 0.02 respectively). Among East Asians (n = 465), carriers of the minor allele in rs1999478 had significantly higher total energy and sugar intakes (1985 vs 1828 kcal/day, p = 0.02 and 113 vs 105 g sugar/day, p = 0.03 respectively). No other associations were observed between AMY1 variants and carbohydrate or starch intake.

Conclusion

Polymorphisms in the AMY1 gene are associated with dietary intake patterns. Identifying the genetic determinants of dietary intake and food preference may enhance our understanding of excessive caloric intake and obesity, a common risk factor of many chronic conditions and provide further evidence to support the use of personalized nutrition recommendations.

Support or Funding Information

Research support from Mitacs
Butyrate Regulates Its Own Metabolic Fate as an HDAC inhibitor in Colorectal Cancer Cells
Authors: Han Anna , MacDonald Amber , Ahmed Bettaieb , Whelan Jay , Donohoe Dallas
Published: November 2023

Butyrate is a metabolite derived from the fermentation of dietary fiber by bacteria in the colon, and it has been implicated in protecting against colorectal cancer. Butyrate is the primary energy source for colonic epithelial cells (colonocytes). Butyrate also regulates gene expression by inhibiting histone deacetylases (HDACs). Both of these fates of butyrate (oxidized as an energy source or HDAC inhibition) are not mutually exclusive. Previously, we show that cancerous colonocytes have a reduced capacity to oxidize butyrate compared to non‐cancerous colonocytes, and this metabolic difference impacts butyrate's role as an HDAC inhibitor. Short chain acyl‐CoA dehydrogenase (SCAD) is a mitochondrial enzyme that mediates the oxidation of butyrate, which is diminished in colorectal cancer. Therefore, we hypothesized that decreased SCAD in colorectal cancer cells results in reduced oxidation of butyrate. Here, we report that butyrate itself suppressed SCAD expression in colorectal cancer cells. Butyrate significantly reduced SCAD expression at the gene and protein level (p<0.05). To test whether this decrease in SCAD impacted metabolism in cancerous colonocytes we used the Seahorse XF24 Analyzer to measure butyrate oxidation. The reduction in SCAD was accompanied by lower butyrate oxidation, thus suggesting that butyrate suppresses its own oxidation in the colorectal cancer cell. To determine if HDAC inhibition was involved in regulating SCAD expression we tested whether a structurally unrelated HDAC inhibitor called trichostatin A (TSA) would mimic butyrate's effect on SCAD. TSA decreased the level of SCAD in a manner similar to butyrate, thus suggesting that the mechanism by which butyrate regulates SCAD is through HDAC inhibition. HDAC1 and HDAC3 are the major HDACs targeted by butyrate and were tested for their role in suppressing SCAD. Interestingly, butyrate did not decrease SCAD expression in non‐cancerous colonocytes, showing that this is a selective effect. These data provide a mechanism as to how butyrate oxidation and function is altered in colorectal cancer.
A Randomized Clinical Trial in Women with Polycystic Ovary Syndrome: Effects of a Pulse‐Based Diet and Exercise Intervention on Blood Lipids, Body Composition and Reproductive Measures
Authors: McBreairty Laura E , Kazemi Maryam , Gordon Julianne J , Pierson Roger A , Chizen Donna R , Chilibeck Philip D , Zello Gordon A
Published: November 2023

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. Clinical symptoms of the syndrome include menstrual irregularities, hyperandrogenism and insulin resistance, and women with PCOS are predisposed to an increased risk of heart disease, diabetes and infertility. Pulse‐based diets (e.g., beans, chickpeas) have insulin lowering effects and we hypothesized that a pulse‐based diet would have a positive effect on serum lipid profiles, body composition as analyzed by dual energy X‐ray absorptiometry, and reproductive measures. Sixty‐one women with PCOS aged 18–35y were randomly assigned to groups receiving a pulse‐based diet (n = 30) or the National Cholesterol Education Program (NCEP) therapeutic lifestyle changes (TLC) diet (n = 31) for 16 wks while participating in an exercise program. Following the intervention, there was a significant time main effect (p < 0.02) and group × time interaction (p < 0.05) in cholesterol ratio (total cholesterol/HDL cholesterol) and LDL cholesterol, with a significantly lower cholesterol ratio (−0.36) and LDL cholesterol level (−0.27 mmol/L) in the pulse‐group following the intervention. Significant group × time interactions were also found in HDL cholesterol (p = 0.009) and triglyceride (p = 0.04), with lower HDL in the TLC‐group (−0.08 mmol/L) and lower triglyceride in the pulse‐group following the intervention (−0.2 mmol/L). There was a time main effect for lower total cholesterol (p = 0.003), fasting insulin (p = 0.04), systolic blood pressure (p = 0.0001) and diastolic blood pressure (p = 0.034), with no differences between groups. We also found a significant time main effect for lower BMI (p = 0.006), whole body fat mass (p = 0.003), trunk fat mass (p = 0.0004), % fat (p = 0.0002), as well as higher % appendicular skeletal muscle mass (p = 0.0006), with no difference in whole body lean mass. Both groups also had a lower antral follicle count in the right ovary (p=0.003) and left ovary (p < 0.001) following the intervention. Lifestyle modifications, including diet and exercise, are currently the first‐line treatment recommended for women with PCOS; however, there are currently no specific diet recommendations for women with PCOS. Our results demonstrate that a pulse‐based diet is more effective than the TLC‐diet for improving cholesterol ratio, LDL cholesterol and triglycerides in women with PCOS.

Support or Funding Information

Supported by Agriculture and Agri‐Food Canada, Saskatchewan Pulse Growers, the Canada Foundation for Innovation, and Saskatchewan Health Research Foundation.
Dissecting the role of timing and caloric intake in energy balance
Authors: Lashinger Laura M , McKenzie Meredith R , Bray Molly S
Published: November 2023

Introduction

CR has been shown to extend longevity and blunt disease progression. One mechanism by which caloric restriction is hypothesized to exert its effects, in addition to simply restricting energy intake, is through entrainment of cellular circadian clocks. Neurohumoral factors released following food intake have been demonstrated to be among the strongest entrainers of molecular clocks, which have been shown to regulate multiple metabolic processes. The purpose of this study was to examine the independent effects of timing versus quantity of macronutrient intake.

Methods

We randomly assigned 48 6‐week‐old male FVB/N mice to low fat (10%kcal from fat; LF) or high fat (45% kcal from fat; HF) diets for 9 weeks. Mice were further randomized within diet to either ad libitum (AL) or 3 timed feeding groups: 2 hr (2H), 4 hr (4H), and 6 hr (6H) food access beginning at zt12 (lights off). Food intake and body weights were measured weekly. Body composition was assessed by MRI, and functional glucose metabolism was assessed by a glucose tolerance test (GTT) at week 9.

Results

Mice exposed to LF diet for 2H (63.7 ± 7.3 kcal) or 4H (73.0 ± 3.8 kcal) ate significantly fewer kcal/wk compared to the 6H (82.6 ± 4.0 kcal) and AL (86.6 ± 6.3 kcal) groups (p<0.001). Consistent with their eating patterns, mice exposed to LF diet for 2H (20.9 ± 2.9 g) or 4H (24.6 ± 1.1 g) had significantly lower body weight (p<0.05) than AL (28.1 ± 2.4 g), although percent body fat was not different between groups. Surprisingly, after controlling for body weight, animals in the 4H (922.0 ± 100.9 AUC) and 6H (913.5 ± 165.7 AUC) groups were significantly less glucose tolerant compared to the AL group (725.0 ± 75.81 AUC; p<0.02). For the HF diet groups, no significant differences were observed in kcal or gram intake; however, mice exposed to the HF diet for 2H (24.6 ± 1.41 g) or 4H (25.8 0.99 g) had significantly lower body weight compared to the 6H (26.6 ± 1.13 g) and AL (28.4 ± 1.48 g) groups. Glucose tolerance was significantly lower in the 4H (901.2 ± 84.4 AUC) and 6H (885.3 ± 63.7 AUC) groups eating HF diets, compared to AL (788.6 ± 67.3 AUC).

Conclusion

Despite equivalent or lower body weight compared to AL‐fed animals, eating in shorter bouts (4 or 6H) resulted in poorer glucose tolerance, regardless of total fat intake.
Added Sugar Intake and Arterial Stiffness in Youth with Type 1 Diabetes: SEARCH Nutrition Ancillary Study
Authors: The Natalie S. , Crandell Jamie L. , Liese Angela D. , Urbina Elaine M. , Couch Sarah C. , Mayer‐Davis Elizabeth J.
Published: November 2023

In the diets of youth, added sugars account for fourteen percent of total calories, with the leading source being sugar‐sweetened beverages (SSB). Among youth with diabetes, fifty percent of youth with diabetes consumed SSB; additionally, higher intakes (≥1 serving per day vs. no intake) were associated with higher levels of total cholesterol, LDL‐cholesterol, and plasma triglycerides. However, the relationship of added sugars on arterial stiffness in youth with diabetes is not known. We examined the association between reported added sugar intake and arterial stiffness using data from the SEARCH for Diabetes in Youth Study, an ongoing multi‐center observational cohort study of youth with diabetes diagnosed at < 20 years of age. Participants included those with physician‐diagnosed type 1 diabetes (T1D) and positive diabetes autoantibody (glutamic acid decarboxylase‐65 or insulinoma‐associated‐2 autoantibodies) at enrollment (n=1,315; diabetes duration mean=10.0 months). Added sugar intake was assessed by food frequency questionnaire and pulse wave velocity (PWV) and augmentation index (AIx) were measured using a SphygmoCor tonometer. PWV was measured from the carotid artery to the femoral artery (PWV truck) and from the carotid artery to the radial artery (PWV arm). Separate, cross‐sectional linear regression models were used to evaluate the association between added sugar and measures of arterial stiffness. Models were adjusted for age, race, sex, household income, clinic site, diabetes duration, insulin regimen, and mean arterial pressure. Additionally, models for PWV were adjusted for heart rate, and models for AIx were adjusted for height. Among youth with T1D, added sugar intake was not associated with PWV arm (β=0.0001; p=0.9) or AIx (β=0.01; p=0.2). However, added sugar intake was positively associated with PWV trunk (β=0.002; p=0.03). The differential associations between added sugar intake and the arterial stiffness measures is expected given that PWV and AIx are not interchangeable measurements. PWV trunk is considered a noninvasive gold standard of arterial stiffness and coronary artery calcification. In contrast, PWV arm is a less robust measure, but may capture peripheral vascular damage, which is common in diabetes; and AIx is a measure of both peripheral and central vascular stiffness and reflects wave reflection and systemic arterial stiffness. Our findings suggest that added sugar intake differentially affect the vascular system, with a positive association on central arterial stiffness. Further research is needed to determine the longitudinal relationship between added sugar intake and arterial stiffness and to identify why added sugar intake may differentially affect the vascular system.

Support or Funding Information

National Institute of Diabetes and Digestive and Kidney Diseases: R01DK077949