bluuebunny/crossref_metadata_2025_split huggingface dataset:
Imaging the cellular dynamics and signals that pattern embryos
Authors: Fraser Scott E. 
Published: June 2021

Advances in cell biology, genomics and proteomics offer unprecedented knowledge of the constituents within cells and the means by which the cells can interact. Advanced imaging techniques provide a powerful means of integrating this growing data set into a mechanistic understanding of the cellular mechanisms that underlie embryogenesis and organogenesis, by studying the events in the intact system. These powerful techniques are challenged by major tradeoffs between spatial resolution, temporal resolution, and the limited photon budget. This combination of requirements is challenging, but necessary: intravital imaging can only generate accurate data on cell lineages and cell migration if it can capture the three dimensional image of the entire embryo or tissue before any of the cells can move half of the distance separating neighboring cells.We are attempting to advance these tradeoffs by constructing faster and more efficient microscopes that maintain subcellular resolution. Our new microscope combines the deep penetration of two‐photon microscopy and the speed of light sheet microscopy (often termed SPIM) to generate images with more than ten‐fold improved imaging speed and sensitivity. This two‐photon SPIM is far less subject to light scattering, permitting subcellular resolution to be maintained far better than conventional light sheet microscopes.
Bent Bone Dysplasia Syndrome defines a nuclear role for FGFR2 in skeletal development
Authors: Merrill Amy Elizabeth , Idoni Brian , Neben Cynthia , Salva Joanna , Roberts Ryan , Krakow Deborah 
Published: June 2021

Development of the skeleton requires dynamic regulation of osteoprogenitor cell renewal and commitment. These processes are dually promoted by Fibroblast Growth Factor Receptor 2 (FGFR2), as evidenced by congenital disorders resulting from FGFR2 mutations. However, how FGFR2 activity balances proliferation and differentiation is unclear. We have identified unique FGFR2 mutations in Bent Bone Dysplasia Syndrome (BBDS), a disorder deficient in osteoblasts despite abundant osteoprogenitor cells. This phenotype of enhanced proliferation and reduced differentiation suggests these FGFR2 mutations uncouple distinct receptor activities in osteoprogenitor cells. The FGFR2 mutations in BBDS reside in the transmembrane domain, prevent receptor incorporation into the plasma membrane, and consequently reduce receptor responsiveness to secreted FGFs. Despite decreased canonical FGF signaling, mutant FGFR2 enhances a noncanonical nuclear function for FGFR2: we found that FGFR2 acts in the nucleolus where it associates with FGF2 and UBF1 to promote ribosomal DNA transcription. This nucleolar association is enriched by mutant FGFR2 and consequently elevates ribosomal RNA levels in the bones of BBDS patients. Delineation of BBDS reveals that nuclear FGFR2 signaling balances osteoprogenitor cell renewal and commitment by regulating ribosome biogenesis.Grant Funding Source: March of Dimes 5‐FY12–166, NIH/NIDCR 5 P30 DE020750‐02
Regulating CTD‐Interactions by Ess1‐Dependent Prolyl Isomerization
Authors: Hanes Steven , Atencio David , Barnes Cassandra 
Published: June 2021

RNA polymerase II directs the synthesis of mRNAs as well as snoRNAs and some snRNAs. The largest subunit, Rpb1, contains an unstructured C‐terminal domain (CTD) composed of multiple repeats of the heptapeptide, Y‐S‐P‐T‐S‐P‐S. These repeats are located near the RNA exit channel and are bound by a variety of protein complexes that function during different stages of transcription and co‐transcriptional RNA processing. Despite the fact that the CTD is relatively long (26 repeats in yeast, 52 in human), different co‐factor complexes are differentially recruited to the CTD during the transcription cycle. Recruitment is regulated by covalent and non‐covalent modification of residues within the CTD repeat. This regulation is referred to as the “CTD code.” Examples of important covalent modifications are phosphorylation of serines at positions 2, 5, and 7.We are studying a non‐covalent modification, the cis/trans isomerization of the peptide bond at phosphorylated Ser5‐Pro6 sites. In yeast, this is carried out by a highly‐conserved enzyme that we discovered called Ess1 (Pin1 in humans). Ess1 binds and isomerizes pSer5‐Pro6, and this has profound consequences for the proper recruitment of proteins (e.g. Nrd1, Pcf11) to the RNAP II complex. Cells that lack Ess1 activity fail to suppress cryptic transcription, and cannot efficiently terminate transcription of small ncRNAs and mRNAs, leading to cell death. Ess1‐dependent isomerization of the CTD also seems to be important for histone modification, as ess1 mutants show reduced levels of H3K4‐ trimethylation. We will discuss potential mechanisms for how Ess1 regulates RNAP II transcription and co‐transcriptional processing.
Vitamin C intake, lead exposure, and oxidative stress in Uruguayan school children
Authors: Roy Aditi , Queirolo Elena , Peregalli Fabiana , Mañay Nelly , Kordas Katarzyna 
Published: June 2021

Oxidative stress (OS) is a potential mechanism for lead (Pb) toxicity. Vit C may modify Pb‐induced OS. This study examined the relation between blood lead level (PbB) and OS markers [8‐isoprostane and 8‐hydroxy‐2‐deoxy Guanosine (8‐oxodg)], and the role of vit C intake in modifying the relation between PbB and OS. 6–8 y old children (n=145) from Montevideo, Uruguay were assessed in a cross‐sectional study, including nutrient intake via two 24 hr recalls. Mean±SD PbB was 4.5±2.1 μg/dL, with 29% children having PbB≥ 5 μg/dL. Specific gravity‐adjusted mean±SD urinary 8‐isoprostane and 8‐oxodg were 1.5±1.2 and 50±32.7 ng/mL, respectively. Mean±SD intake of vit C was 57±54 mg/d, with 23% of children not meeting recommended intake (RDA, 25 mg/d). Children with vit C intake below RDA had higher urinary 8‐isoprstane than children who met RDA (p<0.05). PbB was associated with 8‐isoprostane (β=0.1; p<0.05) even after adjusting for serum ferritin, and vit C and zinc intake. Children in the lowest tertile of vit C intake (<30 mg/d) and PbB above median (>;4.9 μg/dL) had 0.9 ng/mL higher 8‐isoprostane than those in the highest tertile of vit C intake (>;62 mg/d) and PbB below median (p<0.05). PbB was not associated with urinary 8‐oxodg. Low vit C intake and even modest elevation in PbB may predispose children to increased OS.Grant Funding Source: NIEHS Grant 4231251X1
Body fat distribution in preterm and term born children at school age
Authors: Landmann Eva , Huke Verena , Brugger Markus , Strauch Konstantin , Berthold Lars Daniel , Rudloff Silvia 
Published: June 2021

As has been shown for children born small for gestational age, low birth weight due to prematurity might be a risk factor for developing increased body fat mass and a higher percentage of intraabdominal adipose tissue which has been shown to be associated with cardiovascular disease, insulin resistance and finally metabolic syndrome. Thus, body composition and abdominal fat distribution was determined in a total of 236 children aged 5 to 7 years. 116 out of these children were born preterm at a gestational age 29.8 ± 2.6 (30; 24–33) weeks [mean ± SD (median; range)] and 120 children were born at term. Body composition was determined by bioelectrical impedance analysis, percentage of intraabdominal adipose tissue by magnetic resonance imaging. Children born preterm were shorter (120 vs. 123 cm, p = 0.0003) and lighter (21.8 vs. 24.3 kg, p = 0.0001) and had a lower body mass index (15.1 vs. 15.9 kg/m2, p = 0.0025) at the age of 5 to 7 years. Children born preterm neither showed increased fat mass nor intraabdominal adiposity.[Supported by the German Research Foundation (DFG grant no. LA 2428/1–1)]
Polyphenol‐rich red and purple aronia berry extracts inhibit interleukin‐6 from mouse splenocytes.
Authors: Martin Derek , Taheri Rod , Brand Mark , Draghi Andrew , Sylvester Francisco , Bolling Bradley 
Published: June 2021

Viking aronia berries are a rich source of dietary polyphenols, but less is known about other aronia genotypes. The objective of this work was to assess the anti‐inflammatory activity of underutilized aronia berries to relative to Viking. Aqueous acetone extracts were prepared from Aronia melanocarpa (black), prunifolia (purple), and arbutifolia (red) berries (n = 5). Extract polyphenols were quantitated by UPLC‐MS and the total phenols assay. Primary mouse splenocytes were stimulated for 12 h by LPS with berry extracts and interleukin‐6 (IL‐6) was determined in media. On an equivalent total phenols basis, Viking had at least 1.5‐fold greater anthocyanins and proanthocyanidins than other accessions. Phenolic acids were highest in the purple UCO47 and red UCO57 accessions. The UCO57 extract inhibited IL‐6 by 75% and was the most potent among the tested aronia extracts. In contrast, Viking inhibited IL‐6 by 32%. Among all aronia accessions, IL‐6 inhibition was correlated more strongly to phenolic acid and flavonoid content than proanthocyanidin and anthocyanin content. Thus, underutilized aronia accessions have in vitro anti‐inflammatory efficacy, and are promising candidates for evaluation in models of chronic disease.Grant Funding Source: University of Connecticut Diet and Health Initiative
The acute aerobic exercise‐induced increase in amino acid transporter expression adapts to exercise training in older adults
Authors: Markofski Melissa M , Timmerman Kyle L , Dickinson Jared M , Reidy Paul T , Borack Michael , Rasmussen Blake B , Volpi Elena 
Published: June 2021

Exercise and nutritional interventions may prevent or delay frailty and sarcopenia in older adults. The OBJECTIVE of this ongoing study is to determine the acute and chronic effects of aerobic exercise +/− essential amino acid (EAA) supplementation on skeletal muscle amino acid (AA) transporter expression. Preliminary data are reported.METHODSHealthy untrained older adults (65–85 y; n=10) were randomized into one of two groups: exercise and 15 g EAA supplement (Ex+EAA) or exercise and placebo (Ex+Pla). Acute treatment consisted of 45 mins of walking exercise on a treadmill at ~70% heart rate max (Ex+EAA and Ex+Pla) immediately followed by the assigned supplement or placebo. Chronic treatment involved once daily supplementation (EAA or Pla) plus aerobic exercise 3 times/wk. Real‐time qPCR was used to measure mRNA expression of select muscle AA transporters.RESULTSAt baseline, CAT1, SNAT2, PAT1, CD98, and LAT1 mRNA expression increased more after Ex+EAA than Ex+Pla. After chronic treatment, only CD98 increased with Ex+EAA. There were no basal pre to post changes.CONCLUSIONMuscle AA transporter expression increases acutely with Ex+EAA. Exercise training+EAA induces adaptations reducing the acute AA transporter response to these stimuli. Supported by NIH/NIA R01 AG030070 and NIH/NIA R01 AG030070S1Grant Funding Source: NIH
Vitamin D supplementation in healthy adolescents does not increase calcium absorption
Authors: Hill Kathleen M , Martin Berdine R , Laing Emma M , Hausman Dorothy B , Hall Daniel B , McCabe Linda D , McCabe George P , Peacock Munro , Lewis Richard D , Weaver Connie M 
Published: June 2021

Vitamin D supplementation is widely used in adults to increase calcium absorption. The purpose of this study was to determine the effect of vitamin D supplementation in children on calcium absorption at the seasonal nadir of serum 25D. Healthy black and white boys and girls ages 9–13y (n = 295) in the early stages of puberty (sexual maturation stages 2–3) from northern and southern states in the US (40° and 34°N latitudes, respectively) received 0, 400, 1000, 2000, or 4000 IU/d of vitamin D3 by random assignment for 12 weeks during winter. Baseline and 12‐week calcium absorption was determined from an oral dose of stable isotope 44Ca with a breakfast containing 300 mg calcium. Fasting serum 25D was measured by RIA. At baseline, mean serum 25D was 28 ng/mL (interquartile range 23–33 ng/mL) and there was no relationship between serum 25D and calcium absorption. Serum 25D increased with vitamin D3 dose (R2 = 0.50, p < 0.0001), but there was no relationship between increase in serum 25D and calcium absorption. There was no dose effect of vitamin D supplementation on calcium absorption before or after adjusting for pill compliance, race or sex. The results indicate that vitamin D supplementation is not necessary to increase calcium absorption in healthy early pubertal children living in diverse latitudes in the US during winter months.Grant Funding Source: NIH grants HD057126 and RR025761
Leptin and lipids serum concentration on early pregnancy and 2nd and 3rd trimester blood pressure levels: A prospective cohort study in Rio de Janeiro, Brazil
Authors: Kac Gilberto , Farias Dayana Rodrigues , Franco‐Sena Ana Beatriz , de Jesus Thatiana , dos Santos Vaz Juliana 
Published: June 2021

IntroductionLittle is known about lipid profile during pregnancy and 2nd and 3rd trimester blood pressure levels (BPL).ObjectiveTo test the association of lipid profile early in pregnancy and the 2nd and 3th trimester BPL.MethodsProspective cohort of 226 pregnant women followed at 8–13th, 22–24th and 30–34th weeks. The main covariates were total cholesterol, triglycerides, high‐density lipoprotein (HDL‐c), low‐density lipoprotein (LDL‐c) and leptin. The outcome was diastolic blood pressure (DBP) and systolic blood pressure (SBP) variation from the 2nd to the 3rd trimester. Analyses were performed with linear mixed effect models, controlling by obstetric and socioeconomic variables.ResultsTime elapsed between the 2nd and 3rd trimester and pre‐pregnancy body mass index were associated with DBP and SBP. Triglycerides (SBP: β=0.0638, p=0.010), total cholesterol (SBP: β=0.0533, p=0.017; DBP: β=0.0319, p=0.077) and LDL‐c (SBP: β=0.0756, p=0.010; DBP: β=0.0475, p=0.029) were also associated with DBP or SBP. First trimester leptin levels were associated with SBP (β=0.1311, p=0.001) and DBP (β=0.102, p<0.001).ConclusionOur results showed that leptin and lipid profile early in pregnancy might play a role on the BPL change from the 2nd to the 3rd trimester.
Effect of pistachios on lipids, lipoproteins, glucose metabolism, and insulin sensitivity in type 2 diabetes
Authors: Sauder Katherine A , McCrea Cindy E , Kris‐Etherton Penny M , Ulbrecht Jan S , West Sheila G 
Published: June 2021

Controlling blood sugar and dyslipidemia in diabetes is important for reducing cardiovascular morbidity and mortality. This study compared the effect of two diets on lipids, lipoproteins, glucose metabolism, and insulin sensitivity. We enrolled 28 adults with type 2 diabetes in a randomized, crossover, controlled‐feeding study with 4wk diet periods. After a 2 wk run‐in on a typical Western diet, participants consumed a low fat control diet and an isocaloric moderate fat pistachio diet, in which pistachios contributed 20% of energy. At the end of each diet period, we assessed lipid and glycemic parameters while fasted and during a standard 75g oral glucose tolerance test. Compared to baseline, the control diet increased fasting triglycerides (140 vs 164 mg/dl) and the total:HDL cholesterol ratio (4.0 vs. 4.3), but these parameters were unaffected by the pistachio diet (142 mg/dl and 4.0, respectively); this differential response was statistically significant (all p<0.01). Glucose and insulin levels were not affected by the diets; however, glycated hemoglobin was reduced from baseline following both diets, with significantly larger reductions following the pistachio diet than the control diet (6.19% vs 6.02% and 6.07%, respectively, p=0.03). Taken together with other recent studies, these results provide evidence that pistachio consumption can benefit insulin sensitivity in adults with type 2 diabetes.Grant Funding Source: American Pistachio Growers
Fatty acid transport protein 1 mediates macrophage eicosanoid metabolism
Authors: Qin Yuanyuan , Freemerman Alex Jay , Li Lei , Coleman Rosalind , Galanko Joesh , Edin Matthew , Zeldin Darryl , Stahl Andreas , Makowski Liza 
Published: June 2021

The fatty acid transport protein (FATP) is expressed in tissues with active lipid metabolism including macrophages (MPs). FATP1 is a long and very long chain fatty acyl‐CoA synthetase (ACS). Preliminary data in RAW264.7 MPs over‐expressing (OE) FATP1 showed increases in ACS activity along with a blunting of proinflammatory mediators compared to empty vector (EV); while FATP−/− bone marrow derived MPs (BMDMs) displayed blunted ACS activity with elevations in IL‐6, TNFα and MCP‐1 compared to FATP+/+. We hypothesize that FATP1 modulates availability of fatty acids as fuel or as substrates for eicosanoid synthesis. We aim to investigate if FATP1 modulates eicosanoid metabolism and inflammation in MPs. MPs were treated with 5ng/mL LPS and 10 ng/ml IFNγ to polarize to the pro‐inflammatory M1 subtype, or left untreated. Liquid chromatography mass spectrometry results showed FATP1‐OE drove statistically significant increases in PGD2, PGF2α, 8isoPGF2α and TXB2, and decreases in proinflammatory 11, 12, 15‐HETEs, vs. EV. FATP1‐OE also had lower levels of AA compared to EV through metabolomics. Complementary to OE, FATP1−/− displayed elevated 8, 11, 12, and 15‐HETEs. Future directions will examine FATP‐1 mediated oxidation of AA and incorporation into lipids in macrophages. In conclusion, FATP‐1 decreases MPs inflammation potentially through regulation of eicosanoid production. AA017376Grant Funding Source: R00 AA017376
Bioaccessibility of all trans‐Astaxanthin from Salmon
Authors: Chitchumroonchokchai Chureeporn , Failla Mark L 
Published: June 2021

The keto‐carotenoid astaxanthin (AST) is not typically present in human plasma due to its relative scarcity in the human diet. However, the reported health‐promoting properties of AST have aroused interest among both researchers and consumers. Salmon, and especially wild salmon, is the major food source of AST. The purpose of this study was to investigate the digestive stability, bioaccessibility and apical uptake of AST in wild salmon using a couple in vitro digestion and Caco‐2 cell model. All trans‐AST was the predominant carotenoid in wild salmon, whereas commercial AST supplements contain all trans AST‐esters. Recovery of AST following simulated gastric and small intestinal digestion was 88%. Approximately 32% of AST partitioned in the aqueous fraction of chyme during small intestinal of raw and broiled salmon and not altered by inclusion of 2% (vol/wt) soybean oil (31.6 vs 33.8%, respectively). Accumulation of AST by Caco‐2 cells was proportional to duration of incubation and concentration of micellar AST in medium. These data suggest that AST from salmon is highly bioaccessible.Grant Funding Source: Ohio Agricultural Research and Development Center
Lipoprotein Lipase Affects Macrophage Content and Phenotype in Aorta and Adipose Tissue
Authors: Chang Chuchun Liz , Garcia‐Arco Itsaso , Kim Ji Young , Goldberg Ira J , Deckelbaum Richard J 
Published: June 2021

Macrophages (Mq) link inflammation to atherogenesis and insulin resistance. We have reported that dietary n‐3 fatty acids decrease arterial lipoprotein lipase (LpL) and Mq. We now questioned whether LpL can direct tissue Mq trafficking. Transgenic LpL knockout mice rescued with muscle LpL expression (MCKL0) and MCKL0 transplanted with bone marrow (BM) w/ or w/o LpL expression were used to study Mq in aorta and adipose tissue. Immune cells and interacting factors were examined by immunofluorescence, RT‐PCR, or flow cytometry. LpL deletion reduced arterial Mq by >; 30%, which was restored by reconstitution of LpL‐expressing BM. By contrast, in adipose tissue, MCKL0 had a 50% increase in Mq content and >; 5‐fold increase in expression of chemotactic MCP‐1/CCR‐2 and anti‐inflammatory M2 markers (p<0.05). Interestingly, increased Mq‐associated markers were found in adipose tissue and adipocytes, but not in stromal vascular cells, in MCKL0. In blood, MCKL0 have total leukocytes, neutrophils and monocytes ~ 40% lower than control (p<0.05). Inflammatory Gr‐1hi monocytes were decreased by 25%, whereas Gr‐1lo monocytes were increased by 2 fold, in MCKL0 (p<0.05). These data suggest that LpL affects local Mq content and phenotype, in part, via altering immune cell profiling. In the absence of LpL, we hypothesize that a self‐adaptive mechanism that causes adipocytes to produce pro‐inflammatory mediators might exist.Grant Funding Source: NIH‐HL40404 (RJD); T32‐DK007674/HL007343 (CLC)
Estrogens Control Inflammatory Mediators in Experimental Colitis
Authors: Hussein Inaya Abdallah Hajj , Maksoud Rony , Jambart Stephanie , Diab Rami , Assi Tarek Bou , Barada Kassem , Eid Assaad , Jurjus Rosalyne , Reimund Jean‐Marie , Jurjus Abdo 
Published: June 2021

ObjectivesIt is to investigate the effect of Eestrogen (E2) in the management of colitis in a panel of models, focusing on morphological changes, activity of mast cells, expression of cytokines (IL‐1β, IL‐6, and TNF‐α), and extracellular matrix as well as ROS.Materials and Methods200 male Sprague‐Dawley rats, weighing 250 to 300g, were divided into: Group I induced with colitis, not receiving treatment, Group II induced with colitis and treated with estrogen (17β‐estradiol), Group III receiving E2 only, Group IV provided with Saline. In groups I and II colitis was induced according to reported procedures by authors. Daily observations of signs and symptoms were performed. Macroscopic, microscopic evaluations and molecular analysis were done on tissues on days 7, 14, 28 and 56.ResultsThere was amelioration of the estrogen treated rats health: inflammation scores were reduced by 10%, number of mast cells in the colon decreased by 30%, fibronectin expression was only 50%, and collagen IV was minimal or even disappeared completely. There was a significant decrease in TNF‐α. IL‐6, and IL‐1β expression by 25%. In addition, ROS decreased significantly by 30% in the E2 treated rats.ConclusionsThere was improvement in the IBDs inflammatory status in all E2 treated groups at all time points of the experiment. There was, also, less necrosis of tissues as depicted by less collagen IV, fibronectin as well as antioxidant effect.
Characterization of mast cells in the wall of the cerebral arterial systems in the rat and the baboon
Authors: Gichinga Harry N , Miller Kenneth E , Anderson Michael B , Meek Bill D 
Published: June 2021

Rat brain perivascular mast cells have been characterized histochemically and ultrastructurally in other studies (Dimitriadou, 1990). In our earlier studies in the vervet monkey circulus arteriosus, cells resembling mast cells were seen within the tunica adventitia. In our current studies on whole mount preparations of arterial vessels, branching from the circulus arteriosus in both the rat and the baboon, labeling experiments with mast cell tryptase and confocal immunofluorescent microscopy show that mast cells do exist in the wall of the vessels in the two animal species. Fluorescent immunohistochemistry studies of the arterial vessels using serotonin antibody have shown that the mast cells contain serotonin in their granules. Colocalization of mast cell tryptase and serotonin confirmed that these are in the same cell. Colocalization of mast cell tryptase and tryptophan hydroxylase confirmed that serotonin synthesis occurred in the same cell. Other studies will attempt to determine the density of the mast cells in the wall of the vessels.Grant Funding Source: Department of Anatomy and Cell Biology OSU Center for Health Sciences