bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cellular and molecular characteristics of neonatal skin: consequences for healing (734.10)
Authors: Krejci Eliska , Dvorankova Barbora , Kvasilova Alena , Borsky Jiri , Grim Milos , Smetana Karel 
Published: June 2021

Wound healing is a complex and dynamic process of restoring tissue integrity and layers of skin. While in adults healing results in replacement of normal skin structures with scar tissue, the process is scarless during initial periods of prenatal development. Reduced scar formation was also observed shortly after birth.Having the opportunity to obtain newborn skin after corrective surgery of cleft lip, we aimed to compare properties of cellular elements from neonatal and older skin that could be responsible for nearly scarless healing.Cultivated neonatal fibroblasts expressed Nestin, a marker of immature cells, and markers of stem cells Nanog, OCT3/4, SOX2. Neonatal fibroblasts also retained some degree of plasticity as they could be differentiated into adipocytes, smooth muscle cells and chondroblasts but not to osteoblasts.Cultivated neonatal keratinocytes included population of very small cells (4 µm in diameter) exhibiting both epithelial (keratin) and mesenchymal (vimentin) marker, as well as some epidermal stem cell markers.These preliminary data suggest that minimal scarring of neonatal skin could be at least partially explained by persistence of some prenatal properties of cells that retained stem cell characteristics.Grant Funding Source: Supported by GACR project nr. 13‐20293S, PRVOUK project nr. P27/LF1/1 and UNCE project nr. 204013.
Ceramide 1‐phosphate transfer protein depletion in the cell drives autophagic response: potential implications of this newly identified protein in cell death and survival (737.6)
Authors: Mishra Shrawan , Karanjeet Kul , Zou Xianqiong , Hinchcliffe Edward , Brown Rhoderick 
Published: June 2021

Ceramide 1‐Phosphate (C1P) is a biologically active sphingolipid that stimulates cell proliferation, macrophage migration, and inflammatory events. We recently characterized a novel human lipid transfer protein encoded by GLTPD1 on chromosome 1 (locus 1p36.33). We named the protein, ceramide 1‐phosphate transfer protein (CPTP) due to its lipid specificity and discovered that CPTP transports C1P to the plasma membrane from TGN after synthesis by ceramide kinase. CPTP depletion by RNAi leads to C1P accumulation in TGN (~6‐fold), stimulating cPLA2α and inducing pro‐inflammatory eicosanoid production (Simanshu et al., Nature 500: 463‐67, 2013). Here, we investigated whether CPTP depletion leads to programmed cell death and discovered an autophagic response in human cervical cancer cell lines (HeLa) and human lung adenocarcinoma epithelial cells (A549). Transfection with ShRNA (pSuper.GFP.ShRNA.CPTP vector) resulted in GFP‐LC3 puncta and acidophilic acridine orange staining by epifluorescence microscopy and beclin 1(BECN1) overexpression by RT‐PCR. CPTP mutants deficient in C1P binding/transfer (K60A &amp; R106L) also exhibited autophagy. We conclude that normal levels of viable CPTP are needed for cells to suppress autophagy.Grant Funding Source: [Support: NIGMS‐45928 & 72754; Hormel Fnd]
Regulation of Hsf4b nuclear translocation and transcription activity by phosphorylation at threonine 472 (739.2)
Authors: Hu Yanzhong 
Published: June 2021

Hsf4b, a key regulator of postnatal lens development, is subjected to posttranslational modifications including phosphorylation. However, the phosphorylation sites in Hsf4b and their biological effects on the transcription activity of Hsf4b are poorly understood. Here we examined 17 potential phosphorylation residues in Hsf4b with alanine‐scanning assays and found that a T472A mutation diminished Hsf4b‐mediated expression of Hsp25 and αB‐crystallin. In contrast, the phosphomimetic mutation of T472D enhanced their expression. Further investigation demonstrated that Hsf4b could interact with nuclear‐transporter importin β‐1 and Hsc70 via amino acids 246‐320 and 320‐493, respectively. T472A mutation reduced Hsf4b’s interaction with importin β‐1, while enhancing its interaction with Hsc70, resulting in Hsf4b cytosolic re‐localization, protein instability and transcription activity attenuation. At the upstream, MEK6 was found to interact with Hsf4b and enhance Hsf4b’s nuclear translocation and transcription activity, probably by phosphorylation at sites such as T472. Taken together, our results suggest that phosphorylation of Hsf4b at T472 by protein kinases such as MEK6 regulates Hsf4b interaction with the importin β‐1‐Hsc70 complex, resulting in blockade of it nuclear translocation and transcriptional activity of Hsf4b.Grant Funding Source: national nature sciences foundation of china
The c‐RAF/MEK/ERK MAPK pathway regulates a class of GCN2‐independent amino acid response genes (818.6)
Authors: Donelan Will , Shan Jixiu , Kilberg Michael 
Published: June 2021

During adaptation to protein/amino acid (AA) limitation, the general control non‐derepressible 2 (GCN2) serine/threonine protein kinase initiates the amino acid response (AAR) by binding uncharged tRNAs, which activates its kinase activity. Subsequently, GCN2 phosphorylates eukaryotic initiation factor 2 (eIF2) leading to suppression of general protein synthesis, but induction of translation for specific mRNA species, including that for the transcription factor ATF4. ATF4 is a major effector of AAR‐induced transcription for many genes involved in restoring homeostasis or inducing apoptosis. GCN2 is currently the only well characterized sensor for AA deficiency in mammalian cells and the GCN2‐eIF2‐ATF4 pathway is considered the predominant AAR signaling mechanism. However, evidence from several laboratories has been published suggesting that GCN2‐independent AAR signaling exists. In this study, HepG2 human hepatoma clonal cell lines, expressing shRNA against GCN2, were generated to investigate the possibility of alternative AAR signaling mechanisms. Based on previous research, the MAPK pathways were likely candidates and therefore, were screened using chemical inhibitors. Using IL‐8 as a model MAPK‐responsive and AA‐responsive gene, it was established that c‐RAF/MEK/ERK signaling contributes to GCN2‐independent regulation of a wide spectrum of genes following AA limitation.Grant Funding Source: Supported by NIH, DK092062 and DK094729
High dose C‐3 alpha epimer of 25‐hydroxyvitamin D over 8 weeks reduces cortical mineral density of lumbar vertebra in weanling rats (828.2)
Authors: Djekic‐Ivankovic Marija , Mak Ivy , Wang Krystyna , Lavery Paula , Agellon Sherry , Weiler Hope 
Published: June 2021

C‐3 alpha epimer (EPI) of 25‐hydroxyvitamin D (25(OH)D) is elevated in infancy. Short‐term treatment with the EPI of calcitriol reduces parathyroid hormone (PTH) in rats. This study tested the effect of EPI on growth, bone biomarkers and volumetric bone mineral density (vBMD). Weanling rats (4 wk; n=6 male; n=6 female/diet) were randomized to receive AIN‐93G diets modified in vitamin D for 8 wk: control AIN‐93G (C‐1: 25 µg vitamin D3/g diet), control 25(OH)D (C‐2: 12.5 µg 25(OH)D/g diet), level one EPI (EPI‐1: 12.5 µg EPI/g diet) or level two EPI (EPI‐2: 25 µg EPI/g diet). Measures were weight and biomarkers at 0, 4 and 8 wk and in vivo lumbar vertebra 3 vBMD using microcomputed tomography (LCT‐200, Aloka) at 0 and 8 wk. Differences among groups were tested using ANOVA, Tukey’s post hoc test and P<0.05. No differences in vitamin D status as measured using LC‐MS/MS were observed at baseline. Average serum EPI (range ng/ml) at 8 wk was C‐1: 4 (0‐12), C‐2: 2 (0‐7), EPI‐1: 49 (27‐78) and EPI‐2: 98 (41‐173). Weight, ionized Ca and C‐telopeptides of Type 1 collagen were not affected by diet. PTH was lowest in EPI‐2 vs all groups at wk 4; and lower in EPI‐1 and EPI‐2 vs C‐2 at wk 8. Cortical vBMD was lowest in EPI‐2 vs all other groups at wk 8; but not trabecular or total vBMD. These data suggest that pharmacological concentrations of EPI reduce PTH and cortical density during rapid growth.Grant Funding Source: Supported by NSERC and Dairy Farmers of Canada
Anti‐aging and neuroprotective effects of Jambolan (Eugenia jambolana) L. via modulation of stress response signaling in C. elegans (829.26)
Authors: Bezerra Maria , Al‐Ani Maraim , Correia Roberta , Vattem Dhiraj 
Published: June 2021

The effect of Jambolan (Eugenia jambolana) L. spray dried and freeze dried powders (EJP) on modulating stress response signaling was evaluated in transgenic C. elegans carrying promoter‐GFP constructs for several genes in the IGFR/PI3K/AKT, ARE/NRF2 and Sir2.1/AMPK signaling pathways. Relative fold changes in gene expression in response to EJP treatments were quantified flurometrically. Effect of EJP on longevity was evaluated in C. elegans lifespan assays. Anti‐neurodegenerative effects of EJP were evaluated in C. elegans models for Alzheimer’s disease (AD). Where, time to thermally induced Aβ1‐42 aggregation mediated paralysis was evaluated in transgenic C. elegans (CL4176). Results suggest that the processing technology used to produce EJP powders significantly impacted bioactivity. An upregulation in ARE and Sir2.1 stress response genes was noted in response to EJP treatment. A 10‐13% increase in lifespan was observed with EJP treatment. Supplementation with polar acidic, polar basic and polar neutral fractions delayed Aβ1‐42 induced paralysis by 8‐14%.Grant Funding Source: Supported by: Vrdür Foundation (USA) & CAPES (Brazil)
Additon of atorvastatin and lycopene produce hypolipidemic and morphological changes in liver of a NAFLD rat model (829.34)
Authors: Piña Rosa , Ramos‐Gómez Minerva , García Olga , Rosado Jorge 
Published: June 2021

The present study evaluated the effect of atorvastatin (AT) and/or lycopene (LYC) on fatty liver induced with a high‐fat and high‐cholesterol diet (HFHC). Eighty two male Sprague Dawley rats (200 ± 10g) were randomly assigned to 8 groups: normal 4‐weeks (N4), HFHC diet for 4 weeks (model), normal 8 weeks (N8), HFHC diet for 4 weeks followed by 4 weeks of standard diet (DC), HFHC diet for 4 weeks followed by 4 weeks of standard diet plus 50 mg/kg AT (DC+AT50), HFHC diet for 4 weeks followed by 4 weeks of standard diet plus 20 mg/kg LYC(DC+LYC20), HFHC diet for 4 weeks followed by 4 weeks of standard diet plus 50 mg/kg AT and 20 mg/kg LYC (DC + AT50 + LYC20) and HFHC diet for 4 weeks followed by 4 weeks of standard diet plus 20 mg/kg AT and LYC respectively (DC + AT20 + LYC20). Treatments were given daily by oral intubation. Blood samples and livers were taken for the determination of serum lipid profile and histopathological examination. The model group showed a significant elevation of serum TC, TG, HDL and LDL concentrations in comparison with the normal N4 group. Interestingly, DC group showed similar lipid profile than N8 group and we observed no further reduction by the AT and/or LYC treatments. The model group showed steatosis grade II in 25% and grade III in 75% of the livers. In all the treated groups steatosis decreased significantly. In conclusion, AT and LYC improved liver morphology thus suggesting that these treatments have additional benefits than just the change of diet.Grant Funding Source: Partially supported by CONACYT
Organic and conventional farming: differences in polyphenol content and antioxidant activity of lettuce cultivated on developed nature‐friendly compost (830.6)
Authors: Park Jeong‐Eun , Kim Min‐Ah , Kwon Dae Young , Jeong Su‐Jin , Noh Sun‐Ok , So Byung‐Ok , Chae Soo‐Wan , Cha Youn‐Soo 
Published: June 2021

The purpose of this study was to evaluate antioxidant and cancer cell growth inhibition activity by extract nature‐friendly compost, organically and conventionally cultivated lettuce. We determined the anthocyanin, phenol and flavonoid contents and examined antioxidant assay, such as DPPH, ABTS and reducing power. Also, we performed HepG2 cancer cell growth inhibition assay of lettuce extract. The lettuces of nature‐friendly compost and organic exhibited the highest values of antioxidant activity, total polyphenol and flavonoid contents were the highest in nature‐friendly compost lettuce and organic lettuce. In cancer cell growth inhibition activity in a dose‐dependent manner, nature‐friendly compost lettuce extract had growth inhibition activities greater than 90% on HepG2 cell. The results of this study suggest that the antioxidant and anticancer activities in lettuce cultivars grown under nature‐friendly compost and organic conditions are a promising source of functional food ingredients. (This study was supported by a grant (CUHBRI‐2012‐0 2‐007) of the CNUH‐BRI)Grant Funding Source: supported by a grant (CUHBRI‐2012‐0 2‐007) of the CNUH‐BRI
Tart cherry juice increases sleep time in older adults with insomnia (830.9)
Authors: Liu Ann , Tipton Russell , Pan Weihong , Finley John , Prudente Alfredo , Karki Namrata , Losso Jack , Greenway Frank 
Published: June 2021

Recent studies indicate that tart cherries (Prunus cerasus) may have sleep‐enhancing effects. In a randomized crossover trial, we evaluated the effects of tart cherry juice vs. a placebo juice on various markers of sleep quality in older adults (age 68 ± 9 years). Seven participants with insomnia completed two treatment periods (tart cherry juice and placebo juice), 2 weeks each, separated by a 2 week washout period. Participants consumed 8 ounces of juice twice per day. Overnight polysomnography (PSG) was used to evaluate sleep architecture, such as the distribution of sleep stages, sleep latency and state transitions. Participants also completed questionnaires related to sleep, depression, anxiety, and fatigue. Tart cherry juice consumption increased sleep time by 85 ± 17 minutes compared to placebo as measured by PSG (P=0.02). Expression of indoleamine 2,3 dioxygenase (IDO) and PGE2 decreased after tart cherry juice consumption (P<0.05) suggesting that its effects on sleep can in part be ascribed to the improvement in the expression of IDO and PGE2. This work is registered at ClinicalTrials.gov NCT01669317.Grant Funding Source: Supported by the Cherry Marketing Institute
Allele frequency of a 22‐bp insertion/deletion polymorphism of FADS2 in a U.S. population (831.6)
Authors: Kothapalli Kumar , Carlson Susan , O'Brien Kimberly , Ojukwu Kinsley , Zou James , Hyon Stephanie , Ran‐Ressler Rinat , Brenna James Thomas 
Published: June 2021

Introduction. Fatty acid desaturase 2 (FADS2) is a critical rate limiting enzyme in the biosynthesis of long chain polyunsaturated fatty acids (LCPUFA). Recently, we identified a 22 bp insertion/deletion (INDEL) polymorphism within FADS2 intron 1 near a sterol response element to be associated with desaturase expression depending on levels of SREBP‐1c agonists. Cultured lymphocytes from individuals (n=16 Japanese) homozygous for 22 bp deletion (D/D, n=5) showed stronger upregulation of both FADS1 and FADS2 in response to simvastatin. Little is known of the prevalence of this INDEL apart from these 16 Japanese participants.Our aim was to investigate the allele frequency of the INDEL in US residents from 311 opportunistic human samples originating from numerous sites.Methods. A 629 base pair portion of FADS2 intron 1 flanking the sterol regulatory element DNA sequence was amplified by PCR. Amplicons were separated on 2% agarose gels to indentify INDEL genotypes.Results. We identified three genotypes (D/D), (I/D), (I/I) for the 22 bp INDEL for each individual. Our data shows D/D alleles in 43% (n=134), I/D alleles in 39% (n=120) and I/I alleles in 18% (n=57).Conclusion. A high frequency (43%) of D/D genotype is found in US population, when compared to Japanese (24%). Our data indicate that the deletion genotype is prevalent and may contribute to individual variability in response to LCPUFA consumption or statins.Grant Funding Source: NIH R01AT007003
Identification of a conformational epitope induced in the kringle 5‐latent protease domain of Glu‐plasminogen Induced by its interaction with cells (833.2)
Authors: Han Jane , Kim Kee‐Hwan , Parmer Robert , Miles Lindsey 
Published: June 2021

Activation of Glu‐plasminogen is markedly enhanced on cell surfaces, arming cells with the broad spectrum proteolytic activity of plasmin that promotes cell migration. This may be due to conformational changes in Glu‐plasminogen when bound to cells. To explore these conformational changes we have developed anti‐plasminogen mAbs that preferentially recognize receptor‐induced binding sites in Glu‐plasminogen. We used specific proteolysis and immunoaffinity chromatography, followed by LC‐MS‐MS to define the epitope(s) recognized by two mAbs. Plasminogen was digested with trypsin and applied to a normal mouse IgG affinity column and the flow‐through applied to either a mAb 109 or mAb 20 immunoaffinity column. The eluate from the mAb 109 column contained two peaks with masses of 1298 AMU and 1030 AMU in LC‐MS‐MS corresponding to a nonlinear epitope contained within H494‐R504 within the kringle 5 domain and L652‐K661 within the latent protease domain, respectively. For mAb 20, MALDI TOF results were consistent with an epitope contained within L650‐I663, overlapping the mAb 109 epitope. Furthermore, mAb 109 and mAb 20 cross‐reacted in pairwise epitope mapping using surface plasmon resonance. The conformational changes detected by mAbs 109 and 20 are likely to reflect changes in Glu‐plasminogen conformation that modulate its ability to be activated on the cell surface.Grant Funding Source: Supported by HL080146 and CA166473
Targeted mice reveal a role for RAGE in an early inflammatory response to tobacco smoke (834.4)
Authors: Wood Tyler , Winden Duane , Barton David , Betteridge Bryce , Marlor Darek , Wright Alex , Jones Cameron , Chavarria Michael , Rogers Geraldine , Reynolds Paul 
Published: June 2021

The receptor for advanced glycation end‐products (RAGE) has increasingly been demonstrated to be an important modulator of inflammation in cases of pulmonary disease. Published reports involving tobacco smoke exposure have demonstrated increased expression of RAGE, its participation in pro‐inflammatory signaling and its role in irreversible pulmonary remodeling. The current research evaluated the in vivo effects of short‐term tobacco smoke exposure in RAGE null and control mice compared to identical animals groups exposed to room air only. Q‐PCR and immunoblotting revealed elevated RAGE expression in controls after four weeks of exposure and an anticipated absence of RAGE expression in RAGE null mice regardless of smoke exposure. Inflammatory cell behaviors were assessed by determining the activation of ras, intracellular signaling kinases, and cytokine synthesis and secretion. Furthermore, bronchoalveolar lavage fluid (BALF) was procured from RAGE null and control animals prior to assessment for inflammatory cells and molecules. As a general theme, inflammation induced by tobacco smoke exposure was influenced by the availability of RAGE. These data reveal captivating information suggesting a role for RAGE signaling in lungs exposed to tobacco smoke and further research is necessary in order to fully explain roles for receptors such as RAGE in cells coping with exposure.Grant Funding Source: Supported by the Flight Attendant’s Medical Research Institute (FAMRI) and a BYU MEG Award (PRR).
Neural and cell‐cell junction autoantibodies in megacity children: the neurodegenerative impact (835.2)
Authors: Calderon‐Garciduenas Lilian , Vojdani Aristo 
Published: June 2021

Millions of children in the USA, Mexico and around the world are chronically exposed to concentrations of air pollutants, including fine particulate matter, above safety standards. Mexico City children exposed to high concentrations of particulate matter (PM) exhibit a breakdown of the nasal, olfactory, and brain‐blood‐barriers (BBB), along a brain gene imbalance in oxidative stress, inflammation, innate and adaptive immune responses, and the accumulation of misfolded proteins observed in the early stages of Alzheimer (AD) and Parkinson’s diseases.We measure serum autoantibodies associated with epithelial and endothelial barriers, and neural proteins in 95 Mexican children age 11.02 ±3.6 years, with exposures to megacity severe air pollution versus clean air controls. MC children had significantly increased IgG high affinity antibodies for cell‐cell junction and neural proteins including: occludin‐zonulin, actin, S‐100, myelin oligodendrocyte glycoprotein, and myelin basic protein (p<0.001). The major factor determining the impact of brain autoantibodies is the integrity of the BBB, thus, cell‐cell junction and brain autoantibodies might contribute to the white matter integrity alterations, structural/volumetric brain changes and the selective impairment in subscales tapping on attention, short term memory and learning abilities present in highly exposed children. Increasing research supports dysregulated immune responses in the pathophysiology of AD. Early neurodegeneration‐related dysregulated immune responses might indicate pathways that can be targeted for childhood interventions aiming at AD prevention. AD affects 5.2 million Americans today. By 2050, 13.8 million will be affected. Early identification of subjects at risk and effective prevention strategies are urgently needed.
Effect of peripherally restricted PEGylated Neuromedin U on cardiovascular function (837.14)
Authors: Emmerson Paul , Foltz Lisa , Bricker Gerald , Qian Yuewei , Wang He , Suter Todd , Ruble Cara , Flora David , Sundquist Sarah , Statnick Michael , Coskun Tamer , Patel Nita , Leishman Derek 
Published: June 2021

Background: Administration of NMU agonists have been shown to regulate smooth muscle contraction, stress, analgesia, and metabolism. Central NMU receptor activation has been shown to increase heart rate in rodent models. To further examine the effect of peripheral NMU receptor activation on cardiovascular function, a long acting pegylated (40Kda) neuromedin U analog (PEGNMU) was designed and its effect on cardiovascular function examined in rats and cynomolgus monkeys.Methods: cynomolgus monkey NMU receptors were cloned and expressed in HEK293 cells. The activity of NMU peptides was characterized in receptor binding and FLIPR based functional assays. Cardiovascular function was assessed by telemetry in instrumented rats and cynomolgus monkeys.Results: Cynomolgus monkey NMU (cNMU) receptors were >95% homologous to human receptors. NMU peptides activated both human and cynomolgus monkey receptors with similar potency and selectivity. PEGNMU was found to be a potent full agonist at both cNMU receptors and exhibited a half life in cynomolgus monkeys of 33 hours. Administration to rats and cynomolgus monkeys resulted in increased diastolic and systolic blood pressure with no change or slight decrease in heart rate and cardiac contractility.Conclusion: The data presented illustrate a role for peripheral neuromedin U receptors in the regulation of cardiovascular function in vivo.