bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Child‐Administered Food Security Scale is Associated with Household Socio‐Economic Status, Household Food Security and Diet Diversity
Authors: Jamaluddine Zeina , Choufani Jowel , Sahyoun Nadine R , Ghattas Hala 
Published: November 2023

Recent studies have shown that children are able to accurately describe their own experiences of food insecurity, however few studies have quantified this experience, and none have done this in the Middle Eastern context. Informed by a previous qualitative analysis of child food insecurity in Lebanon, we developed a set of items to quantify child food insecurity experience, aiming to develop and validate an Arabic child food security scale (CFSS).Fourteen items were developed and administered as part of a study on food security and nutrition in schools, to 6–16 year old children attending four UNRWA schools for Palestinian refugee (n=1381). We used statistical methods based on Item Response Theory (Rasch model) to assess internal validity of the proposed CFSS. Further validation of the scale was conducted by examining associations through linear and logistic regression with socio‐demographic, economic, household food security and diet diversity variables. STATA 13 and R 3.1.3 were used for data analysis.Three items were dropped from the scale due to high infit statistics and high residual correlation with other items. The resulting 11‐item scale had acceptable reliability (0.77), sensitivity (0.86) and specificity (0.96). CFSS was correlated with household food security score (p<0.001). When categorized into food secure (score 0–2) and food insecure (score 3+), there was 63.6% alignment between child food insecurity and household food insecurity. Food insecure children came from households with lower income (p=0.02) and expenditures per capita (p<0.001), higher household crowding (p=0.004), had less educated mothers (p<0.001), lower household diet diversity (p=0.001) and lower household consumption of meat (p<0.001) and fruit (p<0.001).Child food security in Palestinian refugee schoolchildren in Lebanon was accurately measured through an 11‐item questionnaire and was associated with household socio‐economic status, household food security and diet diversity. This tool is appropriate to assess child food insecurity experience directly with children, and can be used in school‐based interventions, where obtaining data from parents may be cumbersome.Support or Funding InformationThis research was funded by The Nestlé Foundation for the Study of Problems of Nutrition in the World
Zip14‐Mediated Zinc Transport Contributes to Regulation of Glucose Homeostasis in Intestine, Pancreas and Liver
Authors: Aydemir Tolunay Beker , Kim Min‐Hyun , Cousins Robert J. 
Published: November 2023

Zinc influences signaling pathways through controlled targeted zinc transport. ZIP14 is a SLC39 family member zinc transporter which traffics zinc into the cytoplasm. We have previously shown that ZIP14 was the most up‐regulated transporter in models of liver inflammation. Using a Zip14 knockout (KO) mouse model, we further demonstrated that ZIP14 was essential for controlling signaling events for glucose homeostasis and inflammation.Metabolic endotoxemia is one of the major factors contributing to obesity and diabetes, two of the most prevalent metabolic disorders with incidence that is increasing rapidly worldwide. Zip14 KO mice present with signatures of metabolic endotoxemia including elevated serum endotoxin levels due to impaired intestinal barrier function leading to low grade chronic inflammation; increased cytokine expression by metabolic tissues; increased production/secretion of leptin with insulin insensitivity in adipose tissue; and enlarged pancreatic islets with greater serum insulin levels through activation of the MYD88 pathway. In Zip14 KO mice, elevated serum endotoxin levels; insulin insensitivity in adipose tissue; and greater biosynthesis and secretion of insulin from pancreas were returned to control level when mice were treated with antibiotics.Hyperglycemia in type 2 diabetes and obesity is caused by insulin resistance. Insulin resistance results in inhibition of glucose uptake by liver and other peripheral tissues, principally adipose and muscle and with concurrently higher hepatic glucose production. We demonstrate that during glucose uptake the cell surface abundance of zinc transporter ZIP14 and mediated zinc transport increases. Zinc is distributed to multiple sites in hepatocytes through sequential translocation of ZIP14 from plasma membrane to early and late endosomes. Endosomes from Zip14 KO mice contained zinc but were zinc deficient as activities of the zinc‐dependent insulin degrading proteases, insulin degrading enzyme and cathepsin D, were impaired, hence insulin receptor (IR) activity increased. Transient increases in cytosolic zinc levels are concurrent with glucose uptake and suppression of glycogen synthesis. In contrast, Zip14 KO mice exhibited greater hepatic glycogen synthesis and impaired gluconeogenesis and glycolysis related to low cytosolic zinc levels.In conclusion, ZIP14‐mediated zinc transport contributes to regulation of intestinal barrier function, biosynthesis and secretion of insulin by pancreas and endosomal IR activity and glucose homeostasis in hepatocytes. Therefore, modulation of ZIP14 transport activity presents a new target for management of diabetes and other glucose‐related disorders.Support or Funding InformationNIDDK Grant RO1 DK94244
Hepatic Fibrosis is Independent of the Effects of Endotoxin (Lipopolysaccharide) on Hepatic Stellate Cells
Authors: Gandhi Chandrashekhar R 
Published: November 2023

BackgroundBinding of Gram‐negative bacterial endotoxin lipopolysaccharide (LPS) to CD14 is critical for its cellular effects via TLR4. Activation of hepatic stellate cells (HSCs) from its quiescent phenotype to α‐smooth muscle actin (α‐sma)‐expressing fibrogenic and proliferative myofibroblast‐like phenotype is the major mechanism of liver fibrosis of various etiologies. LPS/TLR4 interactions in HSCs were reported to play an essential role in hepatic fibrosis in experimental murine models. However, LPS was found to induce synthesis of nitric oxide and inflammatory cytokines in HSCs without the aid of CD14 or TLR4, suggesting that CD14/TLR4‐independent pathways may play an important role in hepatic pathophysiology. To address this hypothesis, we investigated effects of LPS on HSCs from CD14‐knock‐out (KO) mice and carbon tetrachloride (CCl4)‐induced fibrosis in them.MethodsHSCs derived from wild type (WT) or CD14‐KO mice were stimulated with LPS (100 ng/ml) following their culture‐induced activation. Parameters of fibrogenic activity (expression collagen, α‐sma and fibrogenic cytokine TGFβ1and its receptor) and inflammatory cytokines/chemokines were measured. In vivo, mice were subjected to CCl4 treatment for 4 weeks, and then administered PBS or LPS (5 mg/kg; ip). Liver injury, inflammation and fibrosis were determined.ResultsLPS‐stimulated TNFα expression was greater, IL6 expression similar and IL10 expression lower in CD14‐KO HSCs compared to WT HSCs. Expression of the chemokines Ccl2, Cxcl1 and Cxcl9 also increased similarly in LPS‐stimulated CD14‐KO and WT HSCs. LPS down‐regulated Acta2 (encodes α‐sma), TGFbr1 and collagen 1 expression in both WT and CD14‐KO HSCs, and the inhibitory effects of LPS on α‐sma and collagen 1 in HSCs were not reversed by exogenous TGFβ1. In vivo, CCl4 treatment induced similar liver injury (histology and serum ALT) and fibrosis (Sirius red staining and hydroxyproline content) in WT and CD14‐KO mice. However, administration of LPS following CCl4 treatment increased liver injury and inflammation in WT mice but not in CD14‐KO mice. Essentially similar results were obtained when TLR4‐KO mice were treated with CCl4 and HSCs from TLR4‐KO mice were challenged with LPS.ConclusionThese data suggest that the direct effects of LPS on HSCs are not essential for hepatic fibrosis. In contrast, LPS may play an important role in limiting fibrosis by down‐modulating the critically responsible components in HSCs.Support or Funding InformationThis work was supported by a VA Merit Review Award 1IO1BX001174.
QUANTIFICATION OF SUBSTANCE P IN DORSAL ROOT GANGLION NEURONS IN YOUNG AND ADULT RATS, AFTER NOCICEPTIVE STIMULATION DURING THE NEONATAL PERIOD
Authors: Simoes Ana Leda Bertoncini , Silva Greice Anne Rodrigues , Carmo Elisabeth Cassia , Giorgetto Carolina , Fazan Valeria Paula Sassoli 
Published: November 2023

Substance P (SP) is widely used as a marker for peripheral neurons with unmyelinated fibers. Understanding the plasticity in peripheral pain pathways, even before the stimulus reach the central nociceptive areas is crucial, particularly when noxious stimuli are applied to neonates, when the nervous system is still under remodeling process. We quantified SP immunostained neurons in the dorsal root ganglion (DRG) of male and female Wistar rats 15 and 180 days after nociceptive stimulation [1] during the neonatal period. Right and left L5 DRG were removed, frozen and 8 μm thick criossections were incubated in rabbit polyclonal anti‐substance P antibody (1:5.000; 24hr). Immunostaining protocol was used as described [2]. Labeled neurons were counted and compared between ages, genders and groups. Differences were considered significant if p<0.05. Gender differences were present in both ages, being the number of SP positive neurons in the DRG larger in males on both sides, in animals 15 days old. After 6 months, males showed a larger number of SP positive neurons only on the right side that received the nociceptive stimulus, compared to females. An increased number of SP positive neurons in the DRG of the stimulated side in females was present, immediately after nociceptive stimulation but not after 6 months. In conclusion, neonatal noxious stimulation caused a permanent increase in the SP positive neurons in males that was not observed in females, suggesting that differences in pain sensitivity between genders could be related to morphological alterations of the nervous system.Support or Funding InformationFAPESP, CNPq, CAPES and FAEPA
Studying interaction of the immune and vascular system using intravital multiphoton microscopy
Authors: Zinselmeyer Bernd H , Saunders Brian T , Huang Li‐Hao , Runci Daniele , Williams Jesse W , Randolph Gwendalyn J 
Published: November 2023

With the beginning of the new millennium intravital multiphoton imaging of the immune system has become a necessary tool for understanding cellular behavior in steady state and models of disease, in vivo. The first studies visualized dynamics of antigen presenting cells and T‐cells. Followed by development of fluorescent reporter mice that allowed tracking of neutrophils, monocytes and macrophages, however the spatiotemporal resolution achieved wasn't sufficient enough to study physiological parameters like blood or lymph flow.We have improved our two‐photon imaging approach by decreasing photo toxicity and generated a combination of fluorophores which are low in cytotoxicity, able to label morphological structures and cell populations of interest. This combination of dyes is based on high excitation efficiency capable to be excited with low laser power and bright emission properties. Together with our customized dual femtosecond pulsed laser system (InSight DS+ together with an Mai Tai DeepSee) featuring an ultra‐fast resonance scanner and sensitive hybrid detectors, we can image up to five fluorophores in intravital settings. This approach enables us to visualize lymphatics and blood vessels together with myeloid cells and lymphocytes in vivo examining changes in flow dynamics and cellular interaction (Fig 1).For decades blood vasculature has been studied extensively, but our understanding of lymphatic functions remains poor. Lymphatics interact systemically and locally with the blood vasculature (Fig 2) and using these technique we have recently shown that dendritic cells are an important regulator in lymphatic function (Ivanov et. al. J Clin Invest. 2016 Apr 1;126(4):1581–91.). Many immune‐vasculature interactions can only be proven in the living animal, showing the interactions and impact of immune cells on vascular flow dynamics and vice versa. Our most recent intravital imaging studies allow the visualization of arterial resident macrophage dynamics within atherosclerotic plaque. Additionally, we are utilizing our intravital vascular imaging approaches to address the challenge of determining the role of distinct subsets of myeloid cells in glomerular disease and in murine tumor models (Fig 3). Furthermore, we are hoping these studies help to identify functional interactions of the vasculature and different immune cell populations as therapeutically targets for inflammatory diseases and for the enhancement of cancer immune therapy.Support or Funding InformationBHZ was awarded a Scientist Development Grant (16SDG30480008) from the American Heart Association (AHA) 07/01/16‐06/30/19
Remarkable functional convergence: Type I and II toxin‐antitoxins induce multidrug tolerance by (p)ppGpp‐dependent mechanisms
Authors: Gerdes Ken 
Published: November 2023

Using single‐cell technology, we showed previously that, in Escherichia coli, the ubiquitous bacterial stress alarmone (p)ppGpp (Magic Spot) is a central regulator of both spontaneous and environmentally induced persistence1. The (p)ppGpp level varied stochastically in a population of exponentially growing cells and the high (p)ppGpp level in the rare cells induced persistence. Persister cell formation depended on 10 type II toxin – antitoxin (TA) modules encoding RNases that reversibly inhibit translation by cleavage of mRNA or rRNA2.More recently, another research group showed that a type I TA module (hokB/sokB) of E. coli can induce persistence by a mechanism that also depends on (p)ppGpp and, and surprisingly, the highly conserved GTPase Obg3. Type I TAs encode small proteins that depolarize the cell membrane and confer membrane damage and rapid cell killing when overexpressed. By contrast, moderate expression of Hok toxins depletes the ATP pool and induce drug tolerance4. Expression of these highly toxic proteins is repressed by cis‐acting antisense RNAs5. A complex folding pathway allows the mRNA to escaping irreversible inactivation by the antisense and expression of the toxin in the absence of transcription6,7. However, it is not yet known how (p)ppGpp and Obg induce HokB expression and how the cell recover from Hok‐induced ATP‐depletion and stasis.Nevertheless, these results together reveal Magic Spot as the central regulator and toxin ‐ antitoxins as the central effectors of persister cell formation in E. coli.Support or Funding InformationThis work was supported by the Danish National Research Foundation (grant identifier DNRF120), a Novo Nordisk Foundation Laureate Research Grant and the ERC Advanced Investigator Grant PERSIST (294517).
Daily Mango (Mangifera Indica L.) Consumption for 42 Days Differentially Modulates Metabolism and Inflammation in Lean and Obese Individuals
Authors: Fang Chuo , Kim Hyemee , Barnes Ryan , Talcott Stephen T , Mertens‐Talcott Susanne U 
Published: November 2023

Excess weight and body fat increase the risk of developing multiple medical conditions, including Type 2 Diabetes, cardiovascular diseases, and cancer, which pose major threats to public health. Diets rich in fruits and vegetables have been recommended for preventing metabolic disorder and cardiovascular disease. Mangoes are reported to have high concentrations of polyphenols that exert potent anti‐inflammatory activities relevant to the treatment of chronic diseases and cancer, as demonstrated in preclinical studies. However, the number of human clinical trials examining the metabolic effects of mango polyphenols is limited. This study was carried out to investigate the effects of daily mango consumption for 42 days in lean and obese individuals. In this study, 21 healthy lean (BMI 18–25kg/m2) and obese (BMI>30kg/m2) subjects aged 18–55, were continuously provided with 400g of mango pulp for 42 days. Inflammatory cytokines, metabolic hormones, and lipid profiles were examined in plasma at a baseline and after 42 days of treatment. A three‐day food record was filled out for dietary assessment prior to each clinical visit. Results revealed that 42 days of mango consumption decreased systolic blood pressure (mean ± SD: 119.83±13.16 vs. 115.42±12.33; p<0.05) in lean subjects, but had no significant effect in obese subjects. The level of hemoglobin A1c was improved significantly in obese but not lean subjects. Reduced expression of PAI‐1, associated with reduced risk of atherosclerosis and thrombosis, was observed in both groups (In lean group, mean ± SD: 30.93±18.12 vs. 23.69±17.58; p<0.1; In obese group, mean ± SD: 31.34±8.09 vs. 24.93±12.20; p<0.05). There was a non‐significant trend towards lowered levels of C‐reactive protein, and elevated levels of IL‐10 in both groups. No significant changes were observed in lipid profiles for either group. The consumption of mango did not improve the plasma levels of adipokines. In conclusion, daily mango consumption lowers blood pressure in lean individuals, and benefits obese individuals by maintaining long‐term glucose homeostasis. Galloyl‐derivatives from mango may possess therapeutic potential in the prevention and treatment of obesity and metabolic disorders, which remain to be confirmed in a larger‐size human clinical trial.Support or Funding InformationPartial funding for this research was provided by: National Mango Board
Dairy Products and Iodine‐Containing Supplements Use are Positively Associated with Iodine Status in Childbearing Age Women in the United States
Authors: Arsenault Michelle Ann , Lee Kyung Won , Song Won O. 
Published: November 2023

Iodine is a critical nutrient in the synthesis of thyroid hormone in the body. Although recommended dietary intake of iodine has been established, food composition data of iodine are not available and thus iodine status in population is determined by urinary iodine concentration (UIC). By using food group‐based approach, we reported that dairy products are positive contributors to adequate iodine intake in general adult population in the US. Inadequate iodine status during pregnancy is serious due to fetal neurodevelopment that begins the first trimester of pregnancy. However, little is known on dietary determinants of iodine status in childbearing age women of different race/ethnic groups whose intake of dairy products vary widely. We aimed to describe iodine status and its determinants in childbearing age women of different race/ethnic groups and their associations with dairy product intake. Data from the National Health and Nutrition Examination Survey 2003–2012 were utilized. A total of 2,722 non‐pregnant and non‐lactating women of childbearing age (15–44 years) with information on UIC, single 24‐hour dietary recall, iodine‐containing dietary supplements, salt use, and sociodemographic characteristics were included. Iodine status was assessed by two different WHO criteria (median UIC and the prevalence of UIC <50 μg/L) from single spot urine sample. Multivariable linear regression and logistic regression analyses were conducted after adjusting for covariates. Iodine status of childbearing age women had borderline iodine adequacy (median UIC: 126.6 [117.6–135.6] μg/L). Childbearing age women in the highest tertile of dairy product consumption had lower odds of UIC <50 μg/L (adjusted odds ratio=0.52; 95% confidence interval: 0.30–0.91), compared with those in the lowest tertile. An increase in dairy product intake by 100 g/day led to an increase in UIC by 5% (P <0.01). Taking iodine‐containing supplements and using salt in food preparation were positively associated with UIC (all, P <0.05). However, those older, non‐Hispanic blacks, and highly educated tend to have a lower UIC than their counterparts (all, P <0.05). We found the major driving forces for improving UIC among US childbearing age women were dairy products and dietary supplements with iodine. Childbearing age women should be advised to increase dairy food consumption and iodine‐containing supplement use for achieving adequate iodine intake during subsequent pregnancies. Further studies are needed to identifying dietary and behavioral determinants of iodine status among pregnant and lactating women.Support or Funding InformationThis study was conducted by the generous financial support of the College of Agriculture and Natural Resources Undergraduate Research Program at Michigan State University.
CD47 regulates CD11b‐dependent neutrophil transepithelial migration during intestinal inflammation
Authors: Azcutia Veronica , Luissint Anny‐Claude , Flemming Sven , Quiros Miguel , Nusrat Asma , Luscinskas Francis William , Parkos Charles A. 
Published: November 2023

Inflammatory bowel disease (IBD), including Crohn's disease and Ulcerative colitis, is a chronic, relapsing disorder of the gastrointestinal tract characterized by neutrophil (PMN) associated bystander tissue damage, crypt abscess formation and mucosal ulceration. It is well appreciated that neutrophil transepithelial migration (TEpM) in the intestine correlates with disease flares in individuals with IBD. While the molecular events regulating PMN TEpM are far from understood, it is now clear that the integrin CD11b/CD18 and CD47 play crucial roles in this process. CD47 is a highly glycosylated protein that associates in cis with β1, β2 and β3 integrins in different cell types while also serving as a receptor for Signal Regulatory Proteins (SIRP‐α and ‐γ) and thrombospondin (TSP). CD47 is involved in regulation of innate and adaptive immune responses. For example, it has been reported that PMN recruitment in CD47−/− mice is reduced in models of peritonitis, lung injury and dermal air pouch inflammation, but the exact mechanism(s) behind CD47 regulation of PMN infiltration into inflamed mucosal tissues is unclear. We have previously reported that CD47 expressed in T‐cells regulates transendothelial migration through its physical and functional association with the β2 integrin CD11a/CD18. In the gut, it has been shown that PMN transmigration across intestinal epithelium is dependent on CD11b/CD18 but not CD11a/CD18. Thus, we hypothesized that CD47 interacts with CD11b/CD18 to regulate PMN chemotaxis and TEpM in the intestine. Here we report that CD47 co‐associates with CD11b/CD18 in PMN as determined by co‐immunoprecipitation and proximal ligation assay (PLA). Flow cytometry analyses of murine PMN deficient in CD47 showed that, despite expressing similar levels of CD11b/CD18 at baseline, there was defective upregulation of CD11b/CD18 upon stimulation with the chemoattractants fMLF or LTB4 compared with WT PMN. Additionally, loss of CD47 in murine PMN resulted in a 25% reduction in LTB4 driven chemotaxis. Furthermore, antibody mediated inhibition of CD11b/CD18 reduced WT PMN migration to similar levels as CD47−/− PMN. In contrast, blocking CD11b on CD47−/− PMN did not further reduce migration, suggesting a functional regulation of integrin‐dependent chemotaxis by CD47. In vivo studies modeling PMN TEpM into the intestinal lumen in response to LTB4 revealed decreased migration in CD47−/− mice (>60% reduction vs. WT; p<0.05). Taken together, our data suggest that CD47 plays an important role in PMN intestinal recruitment through regulation of CD11b/CD18 adhesive function. We suggest that CD47 represents a promising new candidate for therapeutic approaches aimed at dampening pro‐inflammatory signals, reducing PMN influx and improving mucosal wound healing in IBD.Support or Funding InformationSupported by NIH 5R01DK079392‐12 and R01HL125780