bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hippocampal Dihomo‐γ‐Linolenic Acid Partially Mediates the Relationship Between Serum Lauric Acid and Hippocampal Choline Metabolites in the Young Pig
Authors: Mudd Austin T , Waworuntu Rosaline V , Berg Brian M , Donovan Sharon M , Dilger Ryan N 
Published: November 2023

Fatty acids are pivotal for growth and development of the neonate, and the brain is especially susceptible to their presence or absence. There is interest in understanding the mechanisms by which specific fatty acids in the circulation influence development, but relatively little research has explored medium chain fatty acids (MCFA) in this context. Therefore, the objective of this exploratory study was to identify novel relationships whereby circulating MCFA levels modulate hippocampal metabolites. Beginning at 2 d and continuing until 30 d of age, 24 vaginally‐derived male piglets were provided custom milk replacer formulated to meet piglet nutrient requirements. At 30 d of age, piglets underwent magnetic resonance spectroscopy (MRS) procedures to quantify metabolite concentrations in the hippocampus. Following MRS, samples from the right hippocampus and serum were harvested from pigs at 31 d of age for lipidomic profiling. Linear regressions were used to assess the relationship between serum MCFA and hippocampal MRS metabolites, as well as between serum MCFA and hippocampal FA. Subsequently, a mediation model was used to investigate whether the relationships between serum MCFA and hippocampal MRS metabolites were mediated by hippocampal FA. The mediation analysis revealed that hippocampal free dihomo‐γ‐linolenic acid (FA‐20:3n6) partially mediated the relationship between serum free lauric acid (FA‐12:0) and brain glycerophosphocholine plus phosphocholine (GPC‐PCh). First, increased levels of serum FA‐12:0 related to decreased levels of hippocampal FA‐20:3n6 (P = 0.011). Second, increased levels of serum FA‐12:0 related to decreased brain GPC‐PCh (P = 0.002). We observed a significant (P < 0.05; 95% CI: −0.245 to −0.019) indirect path of the mediation (i.e., effect of serum FA‐12:0 though hippocampal FA‐20:3n6 on brain GPC‐PCh). Additionally, the direct path (i.e., effect of serum FA‐12:0 on brain GPC‐PCh, accounting for hippocampal FA‐20:3n6) was also significant (P < 0.05; 95% CI: −0.435 to −0.012). Therefore, hippocampal FA‐20:3n6 partially mediated the relationship between serum FA‐12:0 and brain GPC‐PCh. Overall, these results suggest the levels of circulating FA‐12:0 may be related to hippocampal metabolism of previously unrelated complex lipid moieties. Future research should test for direct effects of altering circulating FA‐12:0 on these metabolites and associated roles in brain development and functions.Support or Funding InformationThis project was funded by Mead Johnson Nutrition.
Low Omega‐3 Fatty Acid Status Found in Wellness Screening Participants
Authors: Bird Julia K , Salem Norman , Yurko‐Mauro Karin , Marshall Keri , McBurney Michael I 
Published: November 2023

OBJECTIVE96% of Americans nationally have a sub‐optimal omega‐3 status. The objective of this study was to determine the omega‐3 index and its relationship to diet and dietary supplement use in by volunteers participating in the Healthyroads™ biometrics wellness screening administered at their work site by their employer.METHODS636 employees at 16 DSM worksites in the United States consented to have whole blood, finger stick fatty acid testing as part of their Healthyroads™ wellness biometrics screening, and a second omega‐3 test was offered 3 months later. The research protocol was designed in accordance with the Principles of the Declaration of Helsinki and was approved by the New England IRB (#20160533) before subjects underwent any study‐related procedures. Basic demographics, a validated food frequency questionnaire, and a whole blood sample were collected at baseline and follow‐up. Blood samples were shipped to OmegaQuant LLC for fatty acid analysis and questionnaires for data collation and anonymization. Data were analyzed with SAS version 9.3. At the time of abstract submission, 7 sites and 135 participants had completed a second testing.RESULTS40% (N=252) of participants were female, and 25% (N=161) reported use of dietary supplements containing omega‐3 fatty acids. Participants reported mean intakes of 244±206 (±SD) mg/d EPA+DHA from foods and 183±454 mg/d EPA+DHA from supplements. Mean omega‐3 index (% EPA+DPA+DHA of total fatty acid concentration) was 4.9±0.2%; 29% had an omega‐3 index below 4%, 67% had an insufficient status (4% to 8%) and 3.6% had an adequate status (8% and above).Dietary supplement users' EPA+DHA intakes from food were higher (267±207 mg/d) than dietary supplement non‐users (236±205 mg/d), but this was not statistically significant. Total EPA+DHA intake were significantly higher in dietary supplement users (989±694 mg/d vs 236±205 mg/d, p<0.001).Males had a significantly lower omega‐3 index (4.7±0.1%) than females (5.0±0.1%, p<0.01). Dietary supplement users had a significantly higher omega‐3 index (6.0±0.2%) than non‐users (4.5%±0.1, p<0.001). There was a significant, positive relationship between total EPA+DHA intake and omega‐3 index (β=0.0013, intercept=4.3, p<0.001). For 135 individuals with a follow‐up visit, omega‐3 index was 5.2±0.2%, significantly higher than at baseline (mean increase 0.2%, p=0.03).CONCLUSIONSLess than 5% of employees participating in the Healthyroads™ biometrics wellness screening had an adequate omega‐3 index (>8%). Both regular consumption of fatty fish and use of omega‐3 dietary supplements were associated with higher whole blood concentrations of EPA+DHA. Preliminary findings from a limited number of sites finds that participants who elected to undergo a follow‐up omega‐3 test, after receiving the results from their first test, had taken action to increase their omega‐3 index.
Diet, Nutritional Indicators, Infections and Inflammation Are Associated with Mean Arterial Pressure (MAP) in Indigenous Pregnant and Lactating Women in Rural Panama
Authors: González‐Fernández Doris , del Carmen Pons Emérita , Rueda Delfina , Sinisterra Odalis T , Murillo Enrique , Scott Marilyn E , Koski Kristine G 
Published: November 2023

BackgroundHypertensive disorders of pregnancy (HDPs) are the leading cause of maternal mortality in Latin‐America. Mean arterial pressure (MAP) has been used as an early indicator of HDPs. However, to understand its usefulness in early detection of HDPs, it is important to understand the range of factors associated with MAP in resource poor environments.ObjectiveWe explored associations of MAP or elevated MAP (eMAP) with wood smoke exposure, multiple nutrient deficiencies, infections and inflammation in indigenous Panamanian pregnant and lactating women living in extreme poverty.MethodsA cross‐sectional study recruited 213 pregnant and 99 lactating indigenous women from the Ngäbe‐Buglé Comarca in rural Panama. Information on systolic and diastolic blood pressure (SBP, DBP), environmental and dietary factors, measures of inflammation (C‐reactive protein and cytokines), nutritional status (serum retinol binding protein ‐ RBP, folic acid, vitamins B12, A and D), and several infections (skin, oral, urogenital and intestinal nematodes) was collected. MAP was defined as DBP + 1/3 (SBP‐DBP). eMAP was defined as blood pressure >87 mmHg between 10–18 weeks of gestation, >84 mmHg in weeks 18–34, >86 mmHg after week 34; and ≥95 in lactating women. Bivariate comparisons were followed by adjusted linear and logistic regression models for MAP and eMAP, respectively.ResultsPrevalence of eMAP was 11.2% in pregnancy and 12.1% in lactation. Bivariate comparisons: In pregnancy, MAP was higher in women with folic acid<10 nmol/L, urinary specific gravity (USG)>1020 and hookworm infection, and lower in women with vaginal diplococcal infection and Ascaris. In lactation, MAP was higher in women with USG>1020, intake of animal source foods ≥7/wk and bacteriuria. Regression models: In pregnancy, wood smoke exposure, RBP<30 mg/L, presence of hookworm and TNF‐α were positively associated with MAP whereas basophil numbers, diplococcal infection score and presence of Ascaris were negatively associated with MAP. RBP<30 mg/L, folate deficiency, Trichuris and higher IL‐6 increased the odds of eMAP. During lactation, vitamins B12 and A and bacteriuria were positively associated with MAP whereas animal source foods and bacteriuria increased the odds of eMAP.ConclusionGiven that we identified both positive and negative associations of infections and nutrient deficiencies with MAP and eMAP during pregnancy and lactation, a strategy that simultaneously reduces all infections and all nutrient deficiencies may not be advisable. Rather, a reduction in eMAP may be achieved by reducing wood smoke exposure, treating intestinal nematodes, addressing folate and protein deficiencies in pregnancy, and by treating bacteriuria during lactation.Support or Funding InformationSENACYT (Panama), McGill Vitamin Fund
Diet Macronutrient Composition Impacts White Matter Microstructure in the Brain
Authors: Sawin Emily A , Gonzalez Jose G , Ong Irene M , McIlwain Sean J , Adluru Nagesh , Alexander Andrew L , Yu John‐Paul J 
Published: November 2023

BackgroundDiffusion tensor imaging (DTI) is a noninvasive magnetic resonance imaging‐based method of examining neural structure, organization and white matter integrity.ObjectiveTo determine if (1) diet‐dependent macronutrient composition can impact white matter microstructure in the brain and (2) to determine if changes in diet‐dependent gut microbiome populations correlate with these observed alterations in white matter microstructure.Methods40 weanling male Sprague Dawley rats were randomized to one of four diets, a control diet, a high fat diet, a high fiber diet, or a high protein‐low carbohydrate diet and were fed for three weeks. For each animal, a fecal sample was collected at the beginning of the diet and at the culmination of the study to assess for changes in gut microbiome populations. Neural structure and white matter integrity were assessed by DTI, and transcriptomic changes were assessed with an Affymetrix GeneChip Rat Gene 2.0 ST array.ResultsDiffusion tensor imaging shows diet‐dependent alterations in neural structure, organization, and white matter integrity (Figure 1). The use of advanced modeling and predictive analytics further demonstrate that these observed changes in neural structure, organization, and integrity can be associated with specific microbial populations.ConclusionDiet‐dependent macronutrient composition and corresponding changes in the gut microbiome can influence neural structure and white matter integrity.
Protein Intake and Risk of Prediabetes and Type 2 Diabetes
Authors: Voortman Trudy , Chen Zhangling , Franco Oscar H. 
Published: November 2023

ObjectiveStudies indicated that certain amino acids could affect glucose metabolism. However, few epidemiological studies examined the association between protein intake and risk of type 2 diabetes (T2D), and reported mixed findings. Furthermore, no study examined the association between protein intake and risk of prediabetes and for different types of protein are unclear. Therefore, we aimed to examine the associations of intake of different sources of protein on the development of T2D in large population‐based cohort study.MethodsThe Rotterdam Study is a prospective cohort study of subjects aged 45 years or older in the Netherlands. Prediabetes and T2D were diagnosed on the basis of WHO criteria using medical records and fasting glucose and insulin concentrations, measured in our research center. We included 6805 subjects who were free of T2D at baseline, of whom 5794 were without prediabetes. Protein intake was assessed at baseline with the use of validated food‐frequency questionnaires and expressed in energy percentages (E%). We used multivariable cox proportional hazard regression to analyze the associations between protein intake and risk of prediabetes and T2D. We used nutrient density substitution models to examine macronutrient substitution effects.ResultsDuring a mean follow‐up of 8.0 years, we documented 643 incident cases of T2D among 6805 subjects. For prediabetes, we documented 931 incident cases among the 5794 subjects who were free of prediabetes at baseline, during a median follow‐up of 7.6 years. In multivariable models including age, sex, physical activity, smoking status, education level, diet quality and family history of diabetes, a higher intake of total protein was associated with a higher risk of prediabetes (hazard ratio (HR)=1.19, 95% CI: 1.05–1.34, per 5E%) and a higher risk of T2D (HR=1.35, 95% CI: 1.18–1.54 per 5E%). Results were similar for a higher protein intake at the expense of of lower fat or at the expense of a lower carbohydrate intake. The association of protein was driven by a higher animal protein intake (prediabetes: HR=1.35, 95%CI: 1.20–1.51; and T2D: HR=1.35, 95%CI: 1.18–1.53); and not protein from plant sources. In line with this, a higher intake of animal protein at the expense of plant protein was positively associated with risk of prediabetes and T2D. After additional adjustment for body mass index or waist circumference associations attenuated, but still remained significant.ConclusionsOur results suggest that a higher intake of animal protein, but not plant protein, is associated with a higher risk of developing prediabetes and type 2 diabetes.
Factors Associated with Food Safety Behaviors in Cancer Patients Seeking Treatment
Authors: Paden Holly , Hatsu Irene , Lustberg Maryam , Grenade Cassandra , Kane Kathleen , Mo Kevin , Ilic Sanja 
Published: November 2023

IntroductionOver 14 million Americans suffer from cancer and are at a greater risk of foodborne disease due to weakened immune systems. However, food safety practices and factors that may lead to risky food safety behaviors are not well understood.ObjectiveThe objective of this study is to determine the risk perception and demographic factors associated with food safety behaviors in cancer patients seeking chemotherapy and radiation treatment.MethodsThis was a cross‐sectional study that recruited participants from two cancer‐specific hospitals in Ohio. A 173‐item questionnaire assessed the food acquisition and preparation practices and attitudes toward different aspects of food safety in the cancer population. It included sociodemographic factors, food insecurity status, and disease factors. The data were analyzed in SPSS.ResultsParticipants (n=120) were mostly breast cancer patients (48.1%), female (84.6%), older than 50 (73.1%), and white non‐Hispanic (83.5%). About 38% had a college degree or more and 26.2% had at least one year of college education. A total of 2.9% participants had low food security while 8.7% were marginally food insecure. Low income was associated with risky food acquisition practices, such as buying damaged packages (r=0.318, P<0.01) and expired foods (r=0.310, P<0.01). Other high risk food acquisition practices identified were eating other people's leftovers (33%), eating roadkill (3%), or eating spoiled foods (2%). Low income was associated with unsafe food storage and preparation behaviors, such as storing eggs at room temperature (r=0.434, P<0.01) and leaving cooked foods on the stovetop overnight (r=0.380, P<0.01). Half of the participants were aware that they are at increased risk of contracting foodborne diseases due to cancer. Food insecurity in cancer patients was associated with a decreased risk perception (r=0.262, P<0.01). In general, cancer patients with more children (<18) in the household were more concerned about maintaining their refrigerators at adequate temperatures (r=0.252, P<0.05).ConclusionThe findings can be used to develop effective food safety education programs for cancer patients and highlight the need for food safety education of patients during cancer treatment.Support or Funding InformationFood Innovation Center New Faculty Initiative Award, The Ohio State University
Regulation of Bi‐organellar CHCHD2 in Response to Hypoxia is Dependent upon EGFR Molecular Subtype in Glioblastoma
Authors: Lumibao Jan , Chen Emily , Harley Brendan A , Gaskins H. Rex 
Published: November 2023

Glioblastoma (GBM) is the most common and malignant form of brain cancer in adults, with a median survival time of 12–15 mo. Tumors are heterogeneous and characterized by hypoxic foci. Amplification, overexpression, and mutation of the receptor tyrosine kinase (RTK) EGFR are prevalent in GBM, and the constitutively active EGFRvIII mutant shows the poorest clinical outcomes. However, RTK inhibitors have failed clinically against GBM, with EGFR subtype poorly predicting outcome. We are investigating compensatory signaling pathways active within GBM tumor margins as a possible source of resistance to molecular subtype therapies. Previous studies have reported coiled‐coil‐helix‐coiled‐coil‐helix domain‐containing protein 2 (CHCHD2) as a bi‐organellar protein localized predominantly in the mitochondrial inner membrane but also present in the nucleus where it acts as a transcription factor. We hypothesized that this co‐localization enables GBM cells to adapt to hypoxic stress in the tumor microenvironment, particularly via mitochondrial retrograde signaling. We examined CHCHD2 localization by immunocytochemistry in U87wt and U87vIII (constitutively active EGFRvIII mutant) GBM cells subjected to 24, 48, and 72 h hypoxic (1% O2) incubation. Time‐lapse imaging revealed significantly greater nuclear accumulation of CHCHD2 in U87vIII cells compared to U87wt cells at all hypoxic time points. We next used engineered gliomas formed by microfluidic templating as a model of the GBM microenvironment. RT‐PCR and Western blot analyses revealed increased CHCHD2 gene expression but decreased CHCHD2 protein levels in U87wt cells in 72 h hypoxic incubation compared to normoxic conditions. No changes in CHCHD2 gene expression or protein content were observed in U87vIII cells after 72 h hypoxic incubation. Using the aforementioned engineered gliomas, we observed hypoxia significantly increased GBM invasion and pERK1/2 activation in both EGFRwt and EGFRvIII variants. These data indicate more stable levels of CHCHD2 and greater translocation to the nucleus in U87vIII cells under hypoxic stress, thus impacting downstream genes and pathways and potentially contributing to compensatory oncogenic signaling capable of overcoming RTK inhibition. Additional work will focus on subcellular fractionation and mitochondrial isolation to measure CHCHD2 protein levels in nuclei and mitochondria. EGFRwt and EGFRvIII variant GBM cells with CRISPR‐silenced CHCHD2 are being created to determine the extent to which differential mitochondrial‐to‐nuclear translocation of this bi‐organellar protein in hypoxic U87wt and U87vIII cells contributes explicitly to their enhanced invasion potential and therapeutic resistance.Support or Funding InformationFunding: RO1CA197488
Soft Tissue and Protein Preservation in Dinosaur Fossils: Evidence, Criteria and Implications
Authors: Schweitzer Mary Higby , Zheng Wenxia 
Published: November 2023

Evolutionary change first occurs in the genes or the proteins they encode; thus molecular investigations of extant organisms have transformed our understanding of evolutionary biology. DNA and protein sequence data have been used to test hypotheses of evolutionary relationships, paleobiogeographic trends, rates of molecular change, population mixing, and timing of dispersals. Molecular data have provided insight into population bottlenecks that place species at risk for extinction, and have shed light on species origins, radiations and extinctions, as well as organismal response to climate change at the molecular level. However, the extension of these investigations into deep time is extremely limited; estimates of rate and direction of molecular evolution are currently based upon data derived from living organisms and extrapolated to extinct ones, not directly derived. Remnants of these molecules in fossils allow observation of molecular evolution and diversity across deep time and can reveal molecular traits contributing to adaptation and resilience in the face of these challenges.We present evidence that proteins are preserved in at least two dinosaur specimens that also evidenced still‐soft tissues, discuss the need for rigorous criteria for accepting the identity of biomolecules in deep time, and briefly discuss what these data may mean to our understanding of molecular evolution, species relationships and molecular adaptability over time.Support or Funding InformationNSF INSPIRE Program EAR‐1344198David and Lucile Packard Foundation
Hippo pathway in Heart Development and Regeneration
Authors: Martin James 
Published: November 2023

Heart failure due to cardiomyocyte loss after ischemic heart disease is the leading cause of death in the United States in large part because heart muscle regenerates poorly. The endogenous mechanisms preventing mammalian cardiomyocyte regeneration are poorly understood. Hippo signaling, an ancient organ size control pathway, is a kinase cascade that inhibits developing cardiomyocyte proliferation but has not been studied postnatally or in fully mature adult cardiomyocytes. We investigated Hippo signaling in adult cardiomyocyte renewal and regeneration by inactivating Hippo pathway kinases and adaptor molecules in the post natal and adult heart and performed different types of heart injury. We found that unstressed Hippo‐deficient adult mouse cardiomyocytes re‐enter the cell cycle and undergo cytokinesis. Moreover, Hippo deficiency enhances cardiomyocyte regeneration with functional recovery after postnatal myocardial infarction and cardiac apex resection. In damaged hearts, Hippo mutant cardiomyocytes also have elevated proliferation. We conclude that Hippo signaling is an endogenous repressor of postnatal cardiomyocyte renewal and regeneration and that targeting the Hippo pathway in human disease may be beneficial to treat heart disease.Support or Funding InformationNIH/NHLBI‐R01, Grant # 1R01HL127717‐01A1
Hematopoietic stem cell induction and development
Authors: Zovein Ann Capela 
Published: November 2023

Hematopoietic stem cells (HSC) are generated during embryogenesis from specialized endothelium, termed hemogenic endothelium, in a transient process. We present our recent work dissecting the signaling pathways that regulate hematopoietic versus endothelial fate during hematopoietic stem cell emergence. We demonstrate cell intrinsic and extrinsic signaling are part of the hemogenic program. Arterial fate specifiers are required to be down regulated in hemogenic endothelium, with acquisition of hematopoietic fate determinants in emerging hematopoietic cells, which also exhibit changes in cell cycle dynamics and acquisition of inflammatory mediators. In addition, we explore a possible role of the supporting mesenchyme.Support or Funding InformationThe work was supported by the NIH 1DP2HL117743‐01 Award, and the California Institute for Regenerative Medicine New Faculty award RN3‐06479.