bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent Pulmonary Hypertension of the Newborn is Associated with Remodeling of the Umbilical Vasculature
Authors: Swartz Daniel D , Lakshminrusimha Satyan , Nielsen Lori C , Arter Alison 
Published: June 2021

IntroductionPersistent Pulmonary Hypertension of the Newborn (PPHN) has unknown consequences on systemic vasculature. Soluble elastin peptides derived from vascular remodeling have been shown to enhance or elicit a systemic inflammatory response. We studied the association between pulmonary vascular remodeling in PPHN and umbilical vessel remodeling.MethodsPregnant ewes underwent fetal ductal ligation at 126‐128d gestation (term 145d) to induce PPHN (Morin et al, 1989). The lambs, 8‐9 days later, were then delivered by cesarean section and the umbilical cord was clamped and cut. Cord blood plasma was collected for assay of soluble elastin fragments. Immunohistochemistry and proteomics were performed with paraffin‐embedded and quick frozen umbilical vessels (artery ‐ UA, vein ‐ UV) samples respectively. Umbilical vessel sections were analyzed for cell density, MMP‐2, MMP‐9, and elastin content.ResultsCell density, as well, MMP‐9 and MMP‐2 staining increased in UA and UV of PPHN animals compared to controls. Quick frozen umbilical vascular tissue demonstrated a trend decrease in elastin content. There was an increase in soluble elastin fragments in plasma from PPHN lambs.ConclusionThe umbilical vessels of a surgically created model of PPHN demonstrate vascular remodeling, possibly secondary to soluble factors released from the pulmonary vasculature.
TGF‐Beta is required for retinal vascular barrier function, endothelial cell survival and homeostasis of the adult retina
Authors: Walshe Tony E , Saint‐Geniez Magali , Maharaj Arindel , Sekiyama Eiichi , Maldonado Angel , D'Amore Patricia 
Published: June 2021

Cell‐cell interactions are critical to both vascular development and vessel stability in the adult and TGF‐β signaling between endothelial and underlying mural cells is a potent stabilization signal for the quiescent vasculature. Here we describe the effects of inhibition of TGF‐β signaling in the retinal vasculature by overexpressing soluble endoglin (sEng). TGF‐β inhibition increased vascular and neural cell apoptosis in the inner layers of the retina as determined by TUNEL staining, transmission electron microscopy and western blotting for cleaved caspase 3, concomitant with a decrease in inner retinal visual function as measured by electroretinogram (ERG). We further demonstrate impaired inner retinal vascular perfusion, retinal capillary collapse and an impaired ability to autoregulate peripheral blood flow in response to acetylcholine (ACh). Fundus angiography and evans blue permeability tests revealed increased circulating sEng causes breakdown of the blood‐retinal‐barrier due to a decrease in association of tight junction proteins zo‐1 and occludin. In vitro, inhibition of TGF‐β signaling leads to endothelial but not 10T1/2 cell death and dissociation of endothelial and 10T1/2 cells, concomitant with a breakdown of endothelial barrier function. Our results demonstrate a potent role for endogenous TGF‐β signaling in the quiescent retinal vasculature.Grant Funding SourceNIH
Upregulated placenta growth factor expression in human myocardium is associated with cardiomyocyte damage
Authors: Torry Ronald J. , Labarrere Carlos A. , Baldridge Lee Ann , Miller Steven J. , Torry Donald S. 
Published: June 2021

The usefulness of plasma PlGF as a biomarker of acute coronary syndrome patient outcomes has been described, however little is known regarding its expression and localization in human myocardium.Right endomyocardial biopsies were obtained from donor hearts and cardiac allograft recipients. Samples were grouped according to the presence or absence of myocardial fibrin and changes in PlGF mRNA expression, protein localization, cellular infiltrates, cardiac Tn‐I, time since transplant and ISHLT rejection grades were compared between groups.Biopsies (n = 7) with fibrin expressed 1.8‐fold more PlGF mRNA than biopsies without fibrin (n=10; p < 0.03). PlGF protein was localized in cardiomyocytes, extracellular matrix and microvessels in areas of fibrin deposition and not in fibrin‐negative areas. Fibrin‐positive biopsies were also associated with increased cellular infiltrates (p < 0.05) and elevated cardiac Tn‐I titers (p < 0.03). There was no correlation between PlGF mRNA expression and degree of macrophage, T‐cell, or neutrophil infiltrates or rejection grade. PlGF mRNA expression decreased with time since transplantation (R = ‐ 0.792; p < 0.001).Our results show human myocardium expresses PlGF mRNA/protein and its expression increases with cellular and biochemical indices of myocyte damage. These data provide new support that endogenous PlGF could promote cardiac healing. Support: R01‐HD36830 (DT)
A comparison of midline and lateral measures of the middle cranial fossa in hominoid primates
Authors: Ritzman Terrence Bradley , Copes Lynn Erin , Lewton Kristi Lynn 
Published: June 2021

Research has shown that, in primates, cranial base morphology is important to the overall architecture of the cranium, and particularly affects the position of the facial skeleton. In addition, recent studies demonstrate that the morphology of the lateral and midline basicranium in Homo sapiens are not tightly integrated and the lateral basicranium is a more critical determinant of the anatomy of the splanchnocranium. The relationship between the midline and lateral basicranium has not, however, been explored in taxonomically diverse samples of primates. Thus, the current study tests for correlations between midline and lateral measures of the middle cranial fossa (MCF) in a radiographic sample (N=96) of hominoid primates. As the midline MCF houses the pituitary gland and the lateral MCF houses the temporal lobes, this study also tests for interspecific correlations between temporal lobe size and measures of the midline and lateral MCF. Results indicate that midline and lateral measures of the MCF are not tightly correlated and the lateral measures predict temporal lobe size better than midline measures. These results suggest that studies of the relationship between basicranial morphology and facial positioning in primates, including those of fossil hominins, should employ lateral measures of the MCF, rather than those of the midline MCF.Grant Funding Sourcen/a
Morphometry of pedicle and vertebral body in a Mexican population by CT and Fluroscopy
Authors: Guzmán López Santos , Urritua Vega Edgar , De la Garza Castro Oscar , Elizondo Omaña Rodrigo Enrique 
Published: June 2021

To quantify the morphometric characteristics of the pedicles of the lumbar spine in Mexican population. There are not reports about the morphometry of lumbar pedicle in a Mexican population exist.60 cadavers were evaluated by fluoroscopy and CT from L1 to L5. Each vertebral pedicle was measured in the axial, sagittal and coronal planes.Wide variation in pedicle morphology between specimens at each vertebral level was found in the population. Pedicles from the lumbar vertebrae attained dimensions acceptable for 5.5 ‐ 6.5 mm screw diameters. The data in this study indicates that pedicle screws may be used in the lumbar region.
Targeting G‐quadruplex DNA and associated proteins in cell chromatin using specific oligonucleotide probes
Authors: Zhang Huiping , Haegele Joe , Lin Brian , Wang Yuexi , Quinones Gerri , Ligon Lee A , McGown Linda B 
Published: June 2021

Recent bioinformatics studies have suggested strong ties between G‐quadruplex (G4) forming DNA sequences and oncogene expression. Although there is not yet a direct proof that these sequences form G4 structures in vivo, numerous in vitro studies have suggested so.We use G‐rich insulin‐linked polymorphic region (ILPR) located upstream of insulin gene as the model system to tackle this issue. If ILPR's G‐rich strand does form G4 in vivo during certain nuclear processes such as transcription, its complementary C‐rich strand would turn into an open loop in the process. By hybridizing the C‐rich loop with biotinylated oligonucleotides, we are able to capture ILPR's G4 structures and associated proteins directly from cells. Enzyme‐linked immuno‐sorbent assays are then utilized to identify the proteins.This newly developed direct chromatin precipitation method is an important addition to the chromatin analysis toolbox, and should provide new directions in understanding the regulation of oncogenes at molecular level.
How Do Small Heat Shock Proteins Function?
Authors: Rajagopal Ponni , Jehle Stefan , Caputo Christine , Cho Seung‐Hee , Oschkinat Hartmut , Klevit Rachel 
Published: June 2021

We are investigating the structure of human αB‐Crystallin (αB), an archetypal member of the small Heat Shock Protein (sHSP) family using an hybrid solid‐solution state NMR approach and probing functional questions with the α‐crystallin domain that's common to all sHSPs. The polydisperse, ~580 kDa αB is assembled from 20 kDa subunits and has an 89‐residue α‐crystallin domain. We have isolated the α‐crystallin domain (αB10.1) for solution NMR studies and we are using solid‐state NMR to investigate the structure of αB. The dimeric α‐crystallin domain has an unique structure that's maintained in both the isolated and oligomeric forms. The unusual architecture may provide key answers to the functional mechanisms of αB. αB binds cardiac muscle proteins such as desmin and titin more tightly at acidic pH values presumably to maintain filament integrity of these proteins during cardiac ischemia which is accompanied by acidosis. A mutant, R120G‐αB, is associated with desmin‐related cardio‐myopathy. αB10.1 undergoes a sharp pH‐dependent dimer‐monomer transition in contrast to the mutant R120G‐αB10.1. pH‐dependent dissociation of the α‐crystallin domain can lead to disruption of the oligomer assembly, an event that's postulated to be essential for sHSP function. The absence of this dissociation in the mutant abrogates its protective role, thereby explaining its disease association.Funding from NEI, 1R01EY017370
Analogues of cysmethynil that demonstrate improved isoprenylcysteine carboxymethyltransferase (Icmt) inhibition activity and antiproliferative activity in MDA‐MB‐231 breast cancer cells
Authors: Leow Jo Lene , Gorla Suresh Kumar , Wang Mei , Casey Patrick J , Go Mei‐Lin 
Published: June 2021

Many eukaryotic proteins, such as the Ras family of GTPases, contain a C‐terminal CAAX motif which directs the proteins through a three‐step post‐translational process termed prenylation. Icmt catalyzes the methylation of the C‐terminal prenylcysteine found on the prenylated protein, the last step in this process. Many studies have shown that inhibition of Icmt results in mislocalization and impaired function of the prenylated proteins, significantly impacts oncogenic transformation. Cysmethynil, an indole core small molecule inhibitor of Icmt, has been shown to inhibit cancer cell growth in an Icmt‐dependent fashion. Further evaluation of its mechanism of cell death in prostate cancer cells has revealed that the induction of autophagy is a major contributor.In an attempt to optimize activity, lead optimization of the indole core structure of cysmethynil was carried out and a series of structural analogues were synthesized. Evaluation of their enzyme inhibition and antiproliferative activities identified two analogues that show improvement of these properties of cysmethynil while maintaining a favourable drug‐like profile. These findings confirm and enhance our understanding that indole core Icmt inhibitors have significant impact on cancer cell growth and survival, and these new analogues may prove to be better suited for preclinical study of Icmt inhibitors as cancer therapeutics.
Measurement of TNF induced oxidative stress in the paraventricular nucleus using electron paramagnetic resonance spectroscopy
Authors: Mariappan Nithya , Francis Joseph 
Published: June 2021

Recent findings from our lab suggest that TNF plays an important role in sympathoexcitation in heart failure. We have demonstrated that TNF treatment induces oxidative stress and contributes to end organ damage. In this study, we used a novel EPR method to determine whether chronic TNF treatment induces oxidative stress in the paraventricular nucleus of the hypothalamus.Adult male Sprague‐Dawley rats were divided into four groups: control; TNF treatment; TNF + apocynin (APO; 200 μmol/kg); and TNF + TEMPOL (TEMP; 300 μmol/kg). TNF (40 μg/kg) was injected daily for five days. Rats were sacrificed in a CO2 chamber. We used EPR, the most sensitive and definitive method for quantification of free radicals, to determine reactive oxygen species levels in the PVN. EPR is superior to other free radical detection methods in that it allows for the direct measurement of specific free radicals using specific spin probes. The PVN was micro punched and treated with the specific spin probes 1‐hydroxy‐3‐methoxycarbonyl‐2, 2, 5, 5‐tetramethylpyrrolidine (CMH), for the measurement of total reactive oxygen species and superoxide by EPR. Treatment with TNF increased total ROS and superoxide levels in the PVN (p<0.05). In contrast, treatment with the NADPH oxidase inhibitor apocynin or with tempol attenuated the TNF induced oxidative stress. These findings suggest that EPR is a novel and sensitive method for the measurement of free radicals in brain nuclei.
Novel FADS3 Alternative Transcripts Generated By Alternative Splicing
Authors: Park Woo Jung , Kothapalli Kumar SD , Reardon Holly T , Brenna James T 
Published: June 2021

ObjectiveWe report the first multiple transcript variants of a fatty acid desaturase (FADS), FADS3, generated by alternative splicing, and tissue and cell specific expression.BackgroundFatty acid desaturases are enzymes that catalyze the introduction of cis double bonds at specific positions in a fatty acid chain. FADS1, FADS2 and FADS3 are thought to be the key desaturase enzymes involved in the biosynthesis of long chain polyunsaturated fatty acids. Functions of FADS1 and FADS2 are known, however, the function of FADS3 gene product remains unknown.ProcedureThe protein coding region of baboon FADS3 and FADS3 alternative transcripts (AT), were generated from primers synthesized using human and monkey FADS3 cDNA sequences. To analyze the expression levels of each AT, primers bridging the deleted parts of the exons were designed, tested by RT‐PCR and the products were confirmed by sequencing. The expression was analyzed in baboon tissues and in differentiated and undifferentiated human SK‐N‐SH neuroblastoma cells (NB).ResultsAided by ORF Finder, we identified eight AT for FADS3 with 1.34 kb (classical splicing), 1.14 (AT1), 0.77 (AT2), 1.25 (AT3), 0.51 (AT4), 0.74 (AT6), and 1.11 (AT7). In addition we identified an AT of 0.51 kb (AT5) length that has termination codon within the intron 8‐9. FADS3 AT expression is tissue dependent in 12 baboon tissues. NB cells showed reciprocal increases and decreases in expression.ConclusionThis is the first finding of AT of FADS genes. The FADS3 AT are expressed in many tissues and showed changes in response to neuronal cell differentiation.Support: NIH grant GM071534
Effects of novel vegetable sources on liver fatty acids of spontaneously hypertensive rats
Authors: Johnson Melissa , Pace Ralphenia D , Dawkins Norma L , Wang Baowu , Willian Kyle 
Published: June 2021

Purslane, collard greens and sweetpotato greens rich in certain fatty acids and natural antioxidants, may offer some level of protection against cardiovascular diseases. This research investigated the effects of novel vegetable sources on the fatty acid content of liver tissue in spontaneously hypertensive rats (SHR). Four‐week old SHR (N=44) were fed either the standard AIN76 (control) diet, or diets containing 4% purslane, 4% collard greens, or 4% sweetpotato greens for approximately four weeks. Liver fatty acids were extracted by Folch's method using chloroform‐methanol (2:1 vol/vol); fatty acids were then methylated to yield fatty acid methyl esters. Fatty acid methyl esters were separated and quantified using gas chromatography techniques. Fatty acids present included palmitic ranging from 4.4 to 5.8 mg/g, stearic from 4.0 to 5.9 mg/g, linoleic from 3.0 to 4.2 mg/g, oleic from 1.5 to 2.9 mg/g, and arachidonic from 4.1 to 7.5 mg/g on a fresh weight basis. SHRs consuming the 4% sweetpotato greens diet had higher levels of these fatty acids in comparison to the diets containing purslane and collard greens. Recommendations for the prevention of cardiovascular disease should consider the possible beneficial effects of consuming these vegetables as sources of beneficial fatty acids, antioxidants and dietary fiber.This research was supported by Tuskegee University College of Agricultural, Environmental and Natural Sciences.
Better Food choices for mid‐afternoon or mid‐morning snacks
Authors: Vicente Filipa , Pereira Paula Cardoso , Cabrita António Silvério 
Published: June 2021

Food choices are mainly influenced by availability and people preferences. Lack of time is the main excuse to eat in the coffee shop or snack‐bar instead of preparing something at home, the variety and quality offered can be far away from the recommended. In the present study, four options were chosen between many that Portuguese people normally have for a mid‐afternoon or mid‐morning snack: a sandwich, cheese/ham pastry, a bakery products and salty packed snacks (chips).Caloric differences between sandwiches and cheese/ham snacks can by up to 30%, and the snack can have more 40% fat and the salty packed snacks more 60%. A cheese sandwich plus a fruit juice glass can have as many calories as a cheese/ham pastry snack, the satiety and the quality of the ingredients is completely different.Nutritional advice must take into account that is most important to choose between what is available than considering and ideal situation where everybody has time to prepare meals and carry them to their jobs. Learning to choose between snacks everyday can be the key to better compliance in the diet.
The Wnt pathway antagonist DKK1 is upregulated by amino acid deficiency in a human colon cancer cell line.
Authors: Huang Min , Chen Hong 
Published: June 2021

Amino acid response (AAR) pathway is activated when cells are deprived of amino acid. Activation of the AAR pathway causes upregulation of downstream genes. In the present study, we observed that the Wnt signaling pathway, playing an important role in development and tumorigenesis, is involved in this process. DKK1, an antagonist of the Wnt pathway, was significantly induced at mRNA level in the human colon cancer cell line SW480 after the removal of total amino acids and reached the peak of expression at 8hr. A key target of the AAR pathway, asparagine synthetase was also upregulated. Blocking the availability of a single amino acid histidine with histidinol also caused activation of the AAR pathway and led to an increase in DKK1 expression that is similar to total amino acid limitation. Blocking of the phosphorylation of ERk1/2 abolished the induction of DKK1. Analysis of mRNA stability showed that the induction was partly due to transcriptional regulation. Luciferase reporter assay was conducted to map the basal promoter and amino acid responsive element. Chromatin Immunoprecipitation assay was used to define transcription factor binding and chromatin modification induced by amino acid limitation. In conclusion, the present study showed that the Wnt signaling pathway is a potential downstream target of AAR pathway through the regulation of one of the antagonist, DKK1.Grant Funding SourceCIAF
Variation in the methylenetetrahydrofolate dehydrogenase 1‐like (MTHFD1L) gene and cardiovascular disease (CVD) risk
Authors: Wernimont Susan M. , Clark Andrew G. , Stover Patrick J. , Wells Martin T. , Litonjua Augusto A. , Weiss Scott T. , Gaziano J. Michael , Cassano Patricia A. 
Published: June 2021

Two recent genome‐wide association (GWA) studies identified an intronic SNP (rs6922269) in a region of high linkage disequilibrium (LD) in the MTHFD1L gene that was associated with an increased heart disease risk. The present study explored joint genotypes across 6 variants in this LD block in relation to CVD using a nested case‐control design (378 cases, 425 noncases). OR and 95% CI for the joint genotypes were estimated with conditional logistic regression. In HapMap CEU data, certain joint genotypes were found to be unambiguous proxies for the rs6922269 and rs9767752 SNPs, thus these genotypes could be inferred. Participants with combinations that were unambiguous proxies for genotype rs6922269 AA had a 1.27‐fold increased CVD risk vs. genotype GG (95% CI 0.75, 2.1), a finding similar in magnitude to GWA findings, albeit with lower power. The rs9767752 SNP is proximal to an exon, and joint genotypes that were an unambiguous proxy for the CC genotype (vs. TT genotype) at this locus showed the strongest association with CVD (OR 2.28; 95% CI 1.0, 5.1). Joint genotypes representing the rs9767752 CT genotype were associated with a reduced CVD risk (0.79; 95% CI 0.5, 1.3). Overall the results serve as an adequate replication of association between variation in MTHFD1L and CVD. Funding: NIH T32 DK007158‐33 (SMW), G105 NHLBI Resequencing and Genotyping Service (PAC).Grant Funding SourceNIH T32 DK007158‐33 (SMW)
Effect of Omega‐3 fatty acid supplementation and ALOX5 promoter variants on Lipid Profiles in African‐Americans
Authors: Armstrong Patrice , Allayee Hooman , Kelley Darshan , Hartiala Jaana , Stephensen Charles B. 
Published: June 2021

The objective was to determine the effects of omega‐3 fatty acid supplementation and arachidonate 5‐lipoxygenase (ALOX5) gene variants on plasma lipids and lipoprotein particle profiles (i.e. LDL, HDL, & VLDL). We hypothesized that promoter variants in the ALOX5 gene may influence baseline levels and response to supplementation. The study enrolled 116 healthy African‐Americans subjects with specific deletion variants in the ALOX5 promoter (70% female, 20 ‐ 59 yr). This community‐based, double‐blind, controlled intervention trial randomized subjects within genotype in a 6 x 2 design (6 ALOX5 genotypes; allocated to either EPA/DHA supplement or placebo); 98 completed the study. The intervention group received 5.0 g/d fish oil concentrate which contained 3.0g/d EPA/DHA and the placebo group received 5.0 g/d corn/soybean oil for 6 weeks. Supplementation affected total cholesterol and total triglycerides, as well as HDL and VLDL subfractions. In addition, significant differences were seen in VLDL subfractions among ALOX5 genotypes. Our results confirm that EPA/DHA significantly affect plasma lipid profiles and suggest that ALOX5 genotype modifies this response in healthy African‐American adults.This research was supported by the Pfeiffer Foundation, NIH grants R21AT003411, RO1HL079343, & P60MD0222.Grant Funding SourceNational Institutes of Health