bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increase toll‐like receptor 4 expression after ischemia/reperfusion contributes to myocardial apoptosis: role of PI3Kγ/NFκB pathway
Authors: Xu Hu , Xu Xuemei , Zhang Jingchao , Su Zhaoliang , Martin Claudio M. , Rui Tao 
Published: June 2021

This study is to explore increase toll‐like receptor 4 (TLR4) expression and its regulation pathway in the ischemia/reperfusion (I/R) ‐induced myocardial apoptosis.MethodsTLR4 expression, PI3Kγ, NFκB and apoptosis were assessed in cardiac myocytes challenged with an anoxia/reoxygenation (A/R). In vivo, mice were subjected to coronary artery occlusion followed by releasing for myocardial I/R. Myocardial TLR4 expression, apoptosis were evaluated.ResultsA/R challenge resulted in increased TLR4 expression and myocyte apoptosis. Myocytes deficient in TLR4 did not show increase in myocyte apoptosis after A/R. PI3Kγ and p65 (a subunit of NFκB were phosphorylated in cardiomyocytes with A/R. The phosphorylation of p65 occurred after PI3Kγ. A/R‐induced p65 phosphorylation did not occur in myocytes deficient in PI3Kγ. Pretreatment of myocytes with MG132, an inhibitor of NFκB, prevented the A/R‐induced increase in TLR4 expression. I/R resulted in increase myocardial TLR4 expression and apoptosis. I/R‐induced myocardial apoptosis was attenuated in mice deficient in TLR4 and PI3Kγ.ConclusionOur results indicate increase in TLR4 expression contributes to I/R‐induced myocardial apoptosis. PI3Kγ/NFκB signaling pathway is pivotal in regulating TLR4 expression. (HSFO NA 6316)
Inhibition of bone morphogenetic protein protects against atherosclerosis and vascular calcification
Authors: Yao Yucheng , Bennett Brian J , Wang Xuping , Rosenfeld Michael E , Giachelli Cecilia , Lusis Aldons J , Bostrom Kristina I 
Published: June 2021

The bone morphogenetic proteins (BMP), a family of morphogens, have been implicated in atherogenesis as mediators of inflammation and calcification. We investigated the role of altered expression of Matrix Gla Protein (MGP), an inhibitor of BMP, on the development of atherosclerotic lesions and vascular calcification using MGP transgenic or MGP deficient mice bred to apolipoprotein E (Apoe−/−) mice, a model of atherosclerosis. MPG overexpression reduced vascular BMP signaling, which resulted in reduced lesion size, and intimal and medial calcification. It was associated with reduced expression of the activin‐like kinase receptor (ALK)1 and the vascular endothelial growth factor (VEGF), part of a BMP‐activated pathway that also regulates angiogenesis. MGP‐deficiency, on the other hand, strongly enhanced vascular BMP signaling and expression of ALK1 and VEGF. Despite the high propensity of the Apoe−/− mice to develop lesions, lesion formation was minimal in the setting of MGP deficiency, which causes chondroosteogenic differentiation and calcification, suggesting that the abnormal cell differentiation did not allow for lesion formation. Together, our results indicate that vascular BMP signaling is a key regulator in the development of vascular disease, requiring careful control to maintain normal vascular homeostasis.Research support: NIH/NHLBI, AHA.
IL‐19 decreases ox‐LDL induced VSMC activation by suppression of scavenger receptor expression and reduction of ox‐LDL uptake
Authors: Cuneo Anthony A. , Kelemen Sheri , Autieri Michael V. 
Published: June 2021

Atherosclerosis is inflammatory in nature and oxidized low density lipoprotein (ox‐LDL) has activating effects on vascular smooth muscle cells (VSMC). Interleukin‐19 (IL‐19) is a recently described Th2 anti‐inflammatory cytokine. We have previously reported that IL‐19 expression is induced in VSMC by inflammatory cytokines and in arteries by injury. Our hypothesis is that IL‐19 participates in a negative autocrine regulatory feedback mechanism to ameliorate inflammation. The purpose of this study is to determine the molecular mechanism(s) of IL‐19's anti‐inflammatory role in atherosclerosis. IL‐19 decreases the abundance of ox‐LDL induced COX‐2 protein expression. Fluorescently labeled ox‐LDL uptake is inhibited by IL‐19, as determined by flow cytometry and immunocytochemistry. IL‐19 reduces the abundance of LOX‐1 and CX‐CL16 mRNA, VSMC receptors which internalize ox‐LDL. Each of these receptors have AU‐rich elements (ARE) in their 3' UTR which act as binding sites for the RNA‐binding protein HuR, an inflammatory mRNA stabilizing protein. The mRNA stabilizing function of HuR is linked to its cytoplasmic translocation. IL‐19 inhibits HuR protein abundance and ox‐LDL induced HuR cytoplasmic translocation. Together, these data indicate that at least one of IL‐19's anti‐atherosclerotic mechanisms in VSMC involves reduction of ox‐LDL uptake, primarily through reduced scavenger receptor abundance.Work supported by grant HL063810 and HL090885 from NHLBI, and grant 0455562U from AHA, to M.V.A.. A.A.C. received NHLBI Ruth L. Kirchstein Predoctoral fellowship F30HL095329.
Giardia lamblia attenuation of proinflammatory signaling in intestinal epithelial cells is partially dependent on parasitic modulations to the NF‐κB pathway
Authors: Cotton James A , Sayer Heather L , Buret Andre G 
Published: June 2021

Giardia lamblia is a non‐invasive, protozoan parasite that causes diarrheal disease in humans. Intestinal epithelial cells (IECs) do not release proinflammatory mediators, such as interleukin (IL)‐8, following exposure to G. lamblia trophozoites. The nuclear factor κB (NF‐κB) pathway regulates the expression of proinflammatory factors, such as IL‐8, and its inhibition reduces the expression of these mediators.AimsTo determine if human adenocarcinoma (Caco‐2) monolayers, incubated with G. lamblia trophozoites, reduce secreted levels of IL‐8, following stimulation with proinflammatory IL‐1β, and if this reduction occurs through modulations to the NF‐κB pathway.ResultsCaco‐2 monolayers secreted significantly lower levels of IL‐8 when incubated with G. lamblia for 24 hours prior to stimulation with IL‐1β; this result did not require physical contact between trophozoites and monolayers. G. lamblia reduced total levels of the NF‐κB p65 subunit in a strain dependent manner. All strains induced cleavage of p65 into a fragment approximately 37 kDa in size that translocated to the nucleus following IL‐1β stimulation. NF‐κB p65 cleavage requires physical contact between trophozoites and monolayers.ConclusionAttenuation of proinflammatory signaling in IECs incubated with G. lamblia is at least partially dependent on parasitic modulations to the NF‐κB pathway. Funding was provided by NSERC.
Immunolocalization of VEGF and VEGFR 1 & 2 in embryonic lung tissues
Authors: McNeil Rosie Thecla , Maina John N , Kramer Beverly 
Published: June 2021

Eb 2010 AbstractThe role of vascular endothelial growth factor (VEGF) and its receptors 1 and 2 (flt and flk) have been identified in mammalian lung development but there are few studies concerning their role in avian lung. The objective of this study was to determine whether VEGF, flt and flk are expressed in the developing avian lung between stages 20 to 40.Sections, 4 micrometers thick from 4% paraformaldehyde‐fixed, paraffin‐embedded embryonic lung buds and were immunolocalized for the growth factors using standard avidin‐biotin peroxidase immunohistochemical techniques. Mouse kidney and lung were used as positive control tissues.Positive staining for VEGF presented as diffuse cytoplasmic staining which was first observed at stage 27 with the intensity increasing towards stage 40. Staining for flt and flk were however less intense than that of VEGF. We concluded that VEGF, VEGFR1 and VEGFR2 may play significant roles in avian lung development.Grant Funding Source: Faculty Research Grant
Anatomy table conference assessments in place of cadaver practical exams
Authors: Morton David A , Moyle Kimberly A , Livdahl Nicholas S , Albertine Kurt H 
Published: June 2021

A new curriculum was implemented in 2009 at the University of Utah, School of Medicine. Cadaver practical exams were eliminated because of schedule constraints. We replaced those exams with oral assessments performed during weekly table conferences. Learning objectives were provided for each weekly dissection period, detailing the content for which the students were responsible during table conference assessment. Weekly, six dissection groups (4–5 students/group) were randomly selected for a table conference, during which each student was assessed. Each student was assessed four times during the course. The same faculty did the assessments, to increase consistency among assessments. Students were graded on accuracy, depth of understanding, clarity of explanation, and use of the cadaver. Results demonstrate that student participation increased, as did the level of understanding of the objectives and retention of material. In addition, communication skills and use of anatomical terminology improved. We suggest that anatomy table conferences increase student engagement, demonstration of anatomic knowledge, and integration of that knowledge with pathology and physiology.Grant Funding Source: AAA
The Future of Medical Education Research: A Different Way to Analyze Data to Produce More Valid Results/Conclusions
Authors: Lufler Rebecca , Zumwalt Ann , Hoagland Todd 
Published: June 2021

Medical education research has been criticized for producing less than robust results. Perhaps in these studies significant differences exist, but they are being masked by the statistical analyses used. Typical analyses (t‐test, ANOVA) may not be appropriate in medical education research and may be disguising valid results or producing invalid results by not adjusting for confounding variables. Our purpose is to apply two different statistical analyses to the same set of medical education data and compare the outcomes. Using data from a previous study completed by the authors, analysis was completed in two ways: using ANOVA (assumes students are a homogeneous population) and using regression analyses (adjusting for variables that vary among students). ANOVA results showed no differences in practical exam averages across groups of students with different visual‐spatial abilities (VSA). Using regression analysis and adjusting for gender, learning preference, and MCAT scores, there was a significant difference between the performance of students with highest vs. lowest VSA, with adjusted practical exam average scores of 88.4 and 81.9, respectively (p=0.03). These data demonstrate that controlling for characteristic variables of the study population reveal confounding effects otherwise hidden by typical statistical analysis.Grant Funding Source: None
The genesis of the popliteal tendon and the ‘climb’ of the popliteus muscle
Authors: Ghosh Tamojit 
Published: June 2021

Object of StudyThe genesis of the popliteal tendon and the ‘climb’ of the popliteus muscleSummary of ResultsThe present adult morphology of the postero‐lateral aspect of the knee joint requires a good understanding of the evolutionary origin of the popliteal tendon. The popliteus muscle and its tendon originate separately. During evolution they get connected in the way that they are seen in humans. This tendon is not present in reptiles. This work provides proof of the genesis of the popliteus tendon and delineates which of its surrounding structures it evolved from. Origins of the arcuate popliteal ligament and the short lateral ligament are also discussed.Statement of ConclusionsIn lower vertebrates (birds, reptiles and amphibians) there are separate femorotibial and femorofibular joints with separate femorofibular and femorotibial menisci. Both menisci have corresponding meniscal ligaments to the femur above and the fibula and tibia below. The popliteus muscle exists in these lower vertebrates but has no femoral attachment.As evolution progresses the femorofibular joint and its related structures disappear and the fibula recedes from its femoral attachment to a newer and lower attachment on the upper tibia through the proximal tibiofibular joint. The femorofibular meniscus and it's meniscofemoral ligament (which are remnants of the primitive femorofibular joint) get connected as a continuous tendon to the main body of the popliteus muscle. Thus the popliteus gets a new femoral attachment it did not have initially. The popliteus ‘climbs up’ from a sub‐genual position to a newer supra‐genual one aiding upright walking in humans. Crucially, the formation of its tendon is aided by remnants of the femorofibular joint structures which undergo evolutionary recession.Grant Funding Source: Self
FGF regulation of myocardial integrity and angiogenesis
Authors: Murakami Masahiro , Simons Michael 
Published: June 2021

Integrity of cardiac architecture is crucial to normal cardiac physiology. Cardiac remodeling resulting from impairment of myocardial integrity leads to heart failure, through still incompletely understood mechanisms.We have recently described a new role of fibroblast growth factor (FGF) signaling in the adult vasculature: inhibition of vascular FGF signaling leads to disassembly of endothelial junctions, progressing to severe deterioration of vascular integrity. Similarly, using a mouse model of cardiomyocyte‐specific inhibition of FGF signaling, our studies showed that the FGF system controls cardiac junction stability by modifying Connexin 43 and N‐cadherin localization and expression. Concomitantly, these mice presented cardiac hypertrophy and later developed heart failure, leading to premature death. Moreover, in the same mouse model, inhibition of FGF signaling in myocytes also caused decreased capillary density prior to the development of heart failure.Together with recent evidence suggesting that microvascular rarefaction is partly causative to heart failure progression, we concluded that cardiomyocyte FGF signaling is required for the maintenance of cardiac homeostasis through an angiogenesis dependent mechanism. The lack of basal FGF signaling in cardiac myocytes causes a microvessel dropout, thereby leading to the development of heart failure.Supported by NIH HL‐53793
Mechanistic Perspective of Early Vertebrate Cardiogenesis
Authors: Yang Jennifer , Fraser Scott , Lansford Rusty 
Published: June 2021

Vertebrate heart morphogenesis is a complex process that integrates different structures and cell types driven to interact by genetic and epigenetic factors. We have taken an interdisciplinary approach to studying heart formation by combining the power of molecular genetics with advanced optical imaging within living embryos. We have developed multiple transgenic quail lines and novel imaging methods that permit dynamic observation and manipulation of vascular development. Avian embryos are ideal for imaging due to the accessibility at all stages of development outside the vertebrate mother. These embryos also develop hearts with four chambers, allowing for comparative anatomy to study human hearts. Our primary goal is to analyze heart morphogenesis and determine the mechanisms of heart tube formation and the underlying features of heart tube looping.Grant Funding Source: NIH
Antioxidants Increased In Vitro Wound Healing of Nicotine‐Treated Oral Fibroblasts
Authors: Miguel Symone M San , Opperman Lynne A. , Svoboda Kathy K. 
Published: June 2021

ObjectivesSmoking is associated with increased risk for oral health and dental problems. Treatment with antioxidants (AO) can block the production of reactive oxygen species or block its effects, and might be therapeutically valuable in reducing the risk for many dental maladies. The aim of this study is to address the hypothesis that nicotine impairs wound healing by inhibiting cell migration, and that AOs may counteract nicotine effects.MethodsTo test the effects of nicotine and AO compounds on cell migration, the cells were grown to confluence. Cells were pretreated with 6 mM nicotine for two hours and then treated with AOs. Two hours later, a scratch wound assay was performed. The migratory behavior of the wounded cells was recorded every hour for ten hours, using a Nikon‐Biostation. Analysis of the levels of RAC‐GTP at the leading edge of the wound were determined using confocal microscopy.ResultsAO treatment counteracted the inhibitory effects of nicotine and increased migration rates in human gingival fibroblasts and human periodontal ligament cells, the former to a greater extent than the latter. AO compounds increased the level of RAC activation at the leading edge of cells around the wound margin.ConclusionsNicotine impairs migration of gingival and periodontal fibroblasts. Treatment with combinations of antioxidants showed synergistic effects in restoring cell migration after wound creation.Grant Funding Source: Periosciences
Embracing the Information Age: The Science Informatics Major at Montclair State University
Authors: Deremer Dorothy 
Published: June 2021

Innovative computing tools and computational thinking support the information needs for theoretical and applied life sciences. Advances in computer hardware/software, biochemistry, molecular biology, geosciences and mathematical modeling have added computing to the laboratory and field‐based sciences creating interdisciplinary collaborations of science, computer science, and mathematics, that is, science informatics. Bioinformatics in The Human Genome project is perhaps the best known science informatics.Montclair State's B.S. in Science Informatics began in 2002. With biweekly meetings for 1.5 years, 10 faculty members from Computer Science, Biology/Molecular Biology, Chemistry/Biochemistry, and Mathematical Sciences developed the degree. It includes courses in supporting disciplines, a concentration for depth in one of the disciplines, and 16 credits in interdisciplinary Science Informatics courses. The interdisciplinary courses permeate the program from freshman to the senior years. They include internal and external internships, ethics, and research. A faculty Coordinating Council and the Dean of the College oversee the program.The presentation includes a history of Science Informatics development, the content of the concentrations, the details of the interdisciplinary Science Informatics courses, experiences of the Coordinating Council and other faculty, lesson learned, concerns, and future directions for Science Informatics at Montclair State University.
Structural mechanisms of ssDNA/SSB‐processing enzymes
Authors: Keck James L , Marceau Aimee , George Nicholas P 
Published: June 2021

Unwinding genomic DNA to form single‐stranded (ss) DNA is an obligatory step in many DNA replication, recombination, and repair pathways. However, because ssDNA is sensitive to chemical and nucleolytic attack and can self‐associate to form structures that impede genome maintenance, DNA unwinding also presents a potential threat to genomic integrity. To help mediate this risk, cells have evolved ssDNA‐binding proteins (SSBs) that bind and protect ssDNA from biochemical attacks and maintain its single stranded structure. SSB/ssDNA nucleoprotein complexes thus form a common substrate utilized in genome maintenance reactions. Defining how DNA replication, recombination, and repair enzymes recognize and process SSB/ssDNA structures is key to understanding cellular genome maintenance mechanisms.Bacterial SSBs facilitate DNA replication, recombination, and repair processes in part by recruiting diverse genome maintenance enzymes to ssDNA. This function utilizes the C‐terminus of SSB (SSB‐Ct) as a common binding site for SSB's protein partners. The SSB‐Ct is a highly conserved, amphipathic sequence, comprising acidic and hydrophobic elements. I will present our most recent studies that examine the structural mechanisms that support protein interaction with the SSB‐Ct element, focusing on the roles of these interactions in DNA replication.
Correcting for the influence of inflammation improves the accuracy for estimation of iron status among preschoolers in western Kenya
Authors: Grant Frederick , Suchdev Parmi , Cole Conrad R , Ramakrishnan Usha , Flores‐Ayala Rafael , Martorell Reynaldo 
Published: June 2021

Iron status (IS) estimation in high infection areas is difficult due to the effects of infection on indicators of IS. Using data on indicators of IS [(hemoglobin (Hb), zinc protoporphyrin (ZP), ferritin (Ft), transferrin receptors (TfR), and TfR/Ft index)] and subclinical infection [(acute phase proteins; C‐reactive protein (CRP) and alpha glycoprotein (AGP)] on preschoolers, we examined if the use of a correction factor (CF) will improve the accuracy of estimations of iron deficiency (ID).MethodsWe recruited 2340 children (aged 6–59 mos) in cross sectional surveys and obtained blood for Hb, Ft, TfR, ZP, CRP, and AGP measurements.ResultsCRP correlated with AGP (r=0.62; p<0.001), Ft (r=0.40; p<0.001), Hb (r=−0.21; p<0.001) and ZP (r=0.17; p<0.001); AGP correlated with Ft (r= 0.38; p<0.001), Hb (r=−0.2; p<0.001) and ZP (r=0.16; p<0.001). Use of CFs (ratios of median for reference group over each inflammatory group) improved the estimation of IS of the population (p<0.001) when median iron indicators [Hb (108 vs. 111g/L), Ft (19.4 vs. 13.9μg/L), and ZP (142 vs. 126μmol/mol)] and estimated anemia (Hb<110g/L: 54 vs. 45%) and ID prevalences [(Ft<12 μg/L: 32 vs. 43%), (ZP>80μmol/mol: 89 vs. 83%)] of uncorrected and corrected IS indicators were compared.ConclusionCRP and AGP have an impact on the estimation of IS among preschoolers, but the use of a CF is indicated to improve the accuracy for diagnosis of ID.Sources of research support: CDC, Atlanta, GA; and International Nutrition Foundation, Boston, MA.Grant Funding Source: NUTRITION (ASN)
Bioavailability of grape‐derived polyphenolics and implications in Alzheimer's disease prevention and therapy
Authors: Ho Lap , Ferruzzi Mario G. , Janle Elsa M. , Lobo Jessica , Chen Tzu‐Ying , Talcott Stephen T. , Simon Jim , Wu Qing Li , Wang Jun , Cheng Alice , Weaver Connie M. , Percival Susan S. , Pasinetti Giulio Maria 
Published: June 2021

The production and accumulation of β‐amyloid (Aβ) peptides is central to the pathogenesis of Alzheimer's disease (AD). Accumulating evidence suggests that selective bioactive grape‐derived polyphenols may protect against the AD‐type cognitive deterioration, in part, by interfering with Aβ‐mediated neuropathologic mechanisms. Results from our in vitro and in vivo studies suggest that select polyphenolics from red wines and Concord grape juice may inhibit the generation of Aβ peptides and/or the assembly of Aβ peptides into neurotoxic oligomeric Aβ aggregate species. We next explored the pharmacokinetic and bioavailability of red wine and grape juice polyphenolics to gather insights on the identity and bioactivity of specific polyphenolic components that might exert beneficial AD disease‐modifying activity in vivo. Specific polyphenolic derivatives that are bioavailable in the blood and/or in the brain have been identified. Ongoing studies are now exploring the potential role of these bioavailable polyphenolics in mitigating AD‐type neuropathologic and neurodegenerative mechanisms. Results from our studies provide further support for the inclusion of polyphenolics in the diet and the impetus to develop selective polyphenolic compounds for AD prevention and/or therapy.Supports: 1PO1AT004511‐01 Proj.‐1 (LH), 1PO1AT004511‐01 Proj.‐3 (GMP), J.J. Peters VA GRECC Program (GMP).