bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

BACKGROUNDSepsis, 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.METHODSWe 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).RESULTSAged 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.CONCLUSIONSOur 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 InformationJFC 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 InformationThis 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 InformationSupported 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 InformationNational 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 InformationSupported 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

BackgroundGenetic 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.MethodsFasting 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.ResultsAmong 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.ConclusionPolymorphisms 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 InformationResearch support from Mitacs
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 InformationSupported 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

IntroductionCR 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.MethodsWe 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.ResultsMice 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).ConclusionDespite 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.