bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating Novel Roles for Exogenous and Endogenous Galectin‐3 in Controlling Vascular Inflammation
Authors: Gittens Beatrice , Perretti Mauro , Cooper Dianne 
Published: June 2021

Studies in Galectin‐3 (Gal‐3) null mice indicate a role for this β‐ galactoside‐binding lectin in β2integrin‐independent neutrophil recruitment, whilst the recombinant protein induces L‐Selectin shedding and CD11b upregulation in naïve and primed neutrophils. However, its role in leukocyte trafficking in β2‐dependent models has not been systematically addressed.Intravital microscopy of the cremaster muscle was performed in C57BL/6 (WT) or Gal‐3 null mice, following intrascrotal injection of PBS, IL‐1β (30ng), TNF‐α (300ng) or Gal‐3 (200–1000ng) and intravenous administration of anti‐Ly6G to label neutrophils.Treatment with IL‐1β and TNF‐α significantly reduced leukocyte rolling velocities in WT mice, an effect that was absent in Gal‐3 null mice. In addition, a significant reduction in cell emigration was observed in the Gal‐3 null mice treated with IL‐1β. Administration of Gal‐3 to WT mice resulted in a significant reduction in rolling velocity associated with increased numbers of adherent and emigrated leukocytes, approximately 50% of which were Ly6G‐positive neutrophils.These data suggest that Gal‐3 positively regulates leukocyte recruitment in a stimulus dependent fashion in the inflamed microcirculation. This study unveils novel biology for exogenous and endogenous Gal‐3 in controlling vascular inflammation.Supported by British Heart Foundation Studentship FS/10/009/28166
Effects of Garlic (Allium sativum) on indicators of diabetic nephropathy
Authors: Thomson Martha , Al‐Qattan Khaled , Mansour Mohamed H. , Ali Muslim 
Published: June 2021

The anti‐diabetic, antioxidant and anti‐nephropathic effects of an aqueous extract of raw garlic (RGE) were studied in diabetic rats. Diabetes was induced by IP injection of streptozotocin (STZ) and a fasting blood sugar >;300 mg/dl indicated diabetes. Diabetic rats were divided into 2 groups; control and garlic‐treated. RGE was administered daily for 8 weeks. Blood glucose and serum creatinine and urea were elevated in diabetic rats, and lowered by RGE treatment. In contrast, serum and kidney protein and antioxidants, and serum albumin levels were decreased in diabetic rats, and increased in RGE‐treated diabetic rats. Serum insulin levels were decreased over 10 fold in diabetic rats and increased by RGE treatment. In addition, total urine creatinine, protein and albumin were elevated in diabetic animals and decreased by RGE treatment. In contrast, urine urea was decreased in diabetic rats and elevated by RGE treatment. Plasma and kidney antioxidant enzymes (GR, GPx, catalase) were lower in diabetic rats with RGE‐treated diabetic rats having increased activities. Lipid peroxidation (MDA levels) were increased in kidneys of diabetic rats and lowered in RGE‐treated diabetic rats. Urine enzymes (LDH, ALP and NAG) were increased in diabetic controls and decreased in RGE‐treated diabetic rats. Immunochemical analysis of angiotensin receptor expression and localization in kidney tissues indicated that AT1 receptors were up‐regulated and AT2 receptors were down‐regulated in kidneys of diabetic rats, while these changes were reversed in RGE‐treated diabetic rats. Thus, RGE relieved oxidative stress and nephropathy in diabetic rats.The study was supported by KU grant #SL 09/10.
Do babies eat what mothers eat? The relationship between maternal and child dietary diversity in Bangladesh, Vietnam and Ethiopia
Authors: Nguyen Phuong H. , Avula Rasmi , Saha Kuntal K. , Ali Disha , Tran Lan M. , Frongillo Edward A. , Rawat Rahul , Ruel Marie T. , Menon Purnima 
Published: June 2021

Diverse diets are linked to better child growth from 6 mo onwards. Interventions typically focus on educating mothers about the importance and ways of improving child dietary diversity (DD). However, new evidence suggests that maternal and child DD are associated. Data from surveys on mother and child (6–24 mo) dyads in Bangladesh (BD), Vietnam (VN) and Ethiopia (ET) were used to explore the concordance and strength of the association between maternal and child DD and determine if maternal DD can predict child's minimum DD. DD scores were derived from 24‐hour recall of intake of foods from 7 groups. Fair mother/child concordance (kappa = 0.23–0.40) was found for intake of legumes, dairy and eggs in BD and ET; animal‐source foods (0.26) and eggs (0.27) in VN; and vitamin A‐rich vegetables in ET (0.23). Multivariate regression analysis showed a strong association between maternal and child DD in all 3 countries, suggesting that education should focus on improving both maternal and child DD, rather than child DD only, to maximize benefits for both mother and child. The area under the curve values from receiver operating characteristic analysis were greater than 0.7 and significant in all 3 countries, indicating that maternal DD could predict child DD. However, because a standard maternal DD cut‐off point could not be identified, both indicators should be measured in large surveys to accurately estimate mother and child DD.Funding support from Bill & Melinda Gates Foundation, through Alive & Thrive, managed by FHI360
Genome‐wide DNA methylation and gene expression profiles analysis show novel regulatory pathways in alcohol‐related hepatocellular carcinoma
Authors: Udali Silvia , Guarini Patrizia , Ruzzenente Andrea , Guglielmi Alfredo , Ferrarini Alberto , Tononi Paola , Pattini Patrizia , Moruzzi Sara , Delledonne Massimo , Choi Sang Woon , Friso Simonetta 
Published: June 2021

Chronic alcohol consumption is a dietary habit associated to cancer and in particular to hepatocellular carcinoma (HCC) but the mechanisms of alcohol‐related liver carcinogenesis are still incompletely understood. Alcohol is known to interfere with onecarbon metabolism, the methyl transfer reactions occurring in the liver, and consequently with DNA methylation, one of the main epigenetic features related to cancer development.Aim of the present study was to define a possible role for DNA methylation in alcohol‐related HCC in the absence of confounding factors, i.e. mainly hepatitis infections (HBV and HCV).We performed array‐based genome‐wide promoter DNA methylation and gene expression profiles in HCC tissue compared to homologous tumor‐free liver tissue in eight patients undergoing curative surgery. The merging of DNA methylation and gene expression data allowed the detection of 160 hypermethylated‐repressed, 31 hypomethylated ‐induced, 50 hypermethylated‐induced and 56 hypomethylated‐repressed genes. Among the hypermethylated‐repressed genes we identified several candidate tumor‐suppressor genes, six retinol metabolism genes (ADH1A, ADH1B, ADH6, CYP3A43, CYP4A22 and RDH16) and SHMT1 a key gene of one‐carbon metabolism.In alcohol‐related HCC DNA methylation at promoter site appears to regulate the expression of genes involved in retinol and onecarbon metabolism.
Fat‐soluble vitamin status in response to non‐surgical weight loss in overweight post‐menopausal women
Authors: Prokopy Max , Booth Sarah L , Saltzman Edward , Yeum Kyung‐Jin , Nicklas Barbara , Shea M Kyla 
Published: June 2021

Obesity is associated with an increased risk of fat soluble vitamin (FSV) deficiencies. The effect of dietary weight loss on FSV status is uncertain. We measured plasma concentrations of carotenoids, α‐tocopherol, retinol, phylloquinone, and 25‐hydroxyvitamin D (25(OH)D) in 112 overweight post‐menopausal women (mean(SD) BMI=33.1(3.7) kg/m2) who participated in a 20‐week hypocaloric weight‐loss intervention. Mean(SD) weight loss was −12.1(4.5) kg. All women received 200 IU/day vitamin D3. Except for 25(OH)D, the same FSVs were measured in adipose tissue. Using repeated measures ANOVA adjusted for the respective baseline FSV concentration and potential confounders, the following plasma FSVs increased significantly postintervention (all p<0.01): 25(OH)D (median increase 8.0 to 9.0 nmol/l), α‐carotene (0.09 to 0.13 μmol/l), and cryptoxanthin (0.11 to 0.13 μmol/l). The other FSV concentrations in plasma and adipose tissue generally increased but changes were not statistically significant (all p>;0.05). Modest weight loss achieved through caloric restriction was associated with modest increases in some FSV concentrations, although the clinical relevance is uncertain.Grant Funding Source: NIH (grant R01‐AG/DK20583), Wake Forest University Claude D Pepper Older Americans Independence Center (P30‐AG21332), and Wake Forest University General Clinical Research Center (M01‐RR07122).
School‐based nutrition programs are associated with reduced child food insecurity in a longitudinal study among Mexican‐origin mother child dyads in Texas border colonias
Authors: Nalty Courtney , Sharkey Joseph R. , Dean Wesley R. 
Published: June 2021

In 2011, nearly 3.9 million U.S. households with children experienced child food insecurity (CFI) as reported by parents. Yet, proxy reports may underestimate the true CFI prevalence. The study objectives were 1) understand mothers’ and children's (6–11 y) perspectives and experiences of CFI and its seasonal volatility, including the role of school‐based nutrition programs (SNP) and 2) assess CFI discordance among forty eight Mexican‐origin dyads in Texas border colonias. Promotora‐researchers administered standardized Spanish‐language food security instruments to dyads at two points in time during July 2010‐March 2011. Multilevel longitudinal logistic regression measured volatility in CFI while Cohen's kappa (κ) assessed discordance. SNP reduced odds of CFI by 74% (Odds ratio (OR) = 0.26, P < 0.01). Single head of household and Mexican ethnicity were associated with increased odds of CFI (OR = 4.63, P = 0.03) and (OR = 4.47, P < 0.01), respectively. Fair dyadic agreement was observed (κ = 0.21, P = 0.02). CFI lessened from summer to school year while SNP played a significant role. Mothers’ and children's perspectives and experiences of CFI ought to be measured at multiple occasions to obtain an accurate prevalence of the preventable condition.Grant Funding Source: Robert Wood Johnson Foundation Healthy Eating Research
Pulmonary Hypertension Associated with Human Immunodeficiency Virus: Uncovering Viral Evolution via Bioinformatics
Authors: López‐Astacio Robert Alexis , Reno Samantha Marie , Schoen Rachel O. , Castro‐Flores Sonia , Almodóvar Sharilyn 
Published: June 2021

Individuals with Human Immunodeficiency Virus (HIV) are prone to illnesses like pulmonary hypertension (PH), despite the success of antiretrovirals. PH affects more HIV+ individuals (0.05%) than uninfected (0.001%). The causes of HIV‐PH are unknown however, studies suggest that HIV proteins may play a role. Recent studies found specific HIV‐nef mutations associated with the PH phenotype in humans; others suggested that HIV Envelope (Env) induces PH‐like pulmonary vasculopathy in monkeys. We hypothesized that HIV‐PH‐specific mutations may also extend to env: HIV‐PH patients harbor Envelopes more fit to evade the immune system (more glycosylated), and more pathogenic (T‐tropic vs. M‐tropic), compared to controls. Preliminarily, we cloned HIV‐env and nef from blood of eight HIV+ consenting subjects, and analyzed the env and nef sequences in silico, using tools available in the Los Alamos National Lab. We found more glycosylated Env and T‐tropic viruses along with mutations in Nef in HIV‐PH samples, suggesting that mutations in HIV, in the context of Pulmonary Hypertension, may also implicate Env; further studies may confirm dual evolution of HIV Env‐Nef in a larger sample size. These data may help to gain insights into the mechanisms involved in HIV‐Pulmonary Hypertension.This research was supported by UPR‐PRISE (NIH/NIGMS‐R25GM096955), NHLBI K01‐HL103196 (Almodóvar), and R01‐HL083491 (Flores).
Tubulobulbar complexes facilitate basal junction turnover in the seminiferous epithelium
Authors: Du Min , Young J'Nelle , De Asis Marc , Cipollone Jane , Roskelley Calvin , Takai Yoshimi , Nicholls Peter , Stanton Peter , Deng Wanyin , Finlay Brett , Vogl Wayne 
Published: June 2021

Tubulobulbar complexes (TBCs) are cytoskeleton‐related structures that develop at sites of intercellular attachment in the seminiferous epithelium. It is increasingly evident that TBCs found apically in the epithelium play a role in junction internalization, but much less is known about TBCs that form at basal junction complexes. To test the hypothesis that the complexes facilitate basal junction turnover events, we demonstrate that they do form basally in rat Sertoli cells in primary cultures. Morphologically intact tight and gap junctions are observed in basal TBCs in rats. In addition, immunological probes for three types of junction proteins react with linear structures at the light level that we interpret as TBCs, and probes for EEA1 and Rab5 react in similar locations. Significantly, fluorescence staining patterns for actin and claudin‐11 indicate that the amount of junction present is greatly reduced over the time period that TBCs are known to be most prevalent during spermatogenesis. We use transfection techniques on cultured Sertoli cells to show that basal TBCs likely internalize ‘intact’ junctions. On the basis of our findings we present a new model for basal junction remodeling as it relates to spermatocyte translocation in the seminiferous epithelium. Supported by an NSERC Discovery Grant to AWV.Grant Funding Source: NSERC Discovery Grant
Beta‐adrenergic receptors regulate cardiomyocyte proliferation via PI3K/AKT pathway and cell cycle kinases in neonatal mouse heart
Authors: XU Yanchun , Zhang Weizhi , Yano Naohiro , Mao Quanfu , Padbury James , Tseng Yi‐Tang 
Published: June 2021

ObjectiveChronic β‐adrenergic receptor (βAR) stimulation leads to cardiac hypertrophy. We have demonstrated a cardiac βAR‐PI3K crosstalk in adult mouse. Since both cardiac βAR and PI3K signaling activities are developmentally regulated, with high activities in fetal/early newborn stages, this study was set out to elucidate the biological consequence resulted from the βAR‐PI3K crosstalk in neonatal mouse heart.MethodsNewborn (2.5 days old) C57BL/6 mice were treated with propranolol (10 mg/kg, ip) for 1 hr to block βAR. This was followed by treatment with EdU (40 mg/kg, ip) for 4 more hr to monitor cell proliferation. Heart cryosections were processed for double immunofluorescence staining to detect EdU, α‐actinin‐2 and MEF 2A. Cardiac tissue lysates were subject to in vitro lipid kinase assay for measurement of PI3K activity and to Western blotting to measure the expressions of PI3K pathway related proteins and cell cycle machinery proteins.ResultsβAR blockade significantly decreased cardiomyocyte proliferation (*p<0.05). βAR blockade also significantly reduced cardiac PI3K activity, and phosphorylation of its downstream effectors, including Akt (Ser473 and Thr308), GSK‐3α (Ser21), GSK‐3β (Ser9), FOXO1 (Thr24) and FOXO3a (Thr32, Ser253). However, acute βAR blockade did not affect the levels of mTOR/P70S6K/S6 axis and ERK1/2. βAR blockade also decreased the expression of cell cycle related proteins including p‐Chk1, p‐Chk2 and 14–3‐3 proteins, but increased the expression of Myt‐1 and p‐cdc2.ConclusionsOur study suggests a novel mechanism regulating cardiomyocyte proliferation in newborn mouse. This involves the crosstalk from βAR to PI3K signaling pathway and results in alteration in cell cycle.
Visual correlation between iron, amyloid‐beta, and tau depositions in the medial temporal lobe of Alzheimer's disease post‐mortem brains
Authors: Stone Megan Alicia , Bridgewater James , Kavafyan Talar , Steed Kevin , Salin Megan , Saline Ashley , Barzee Brigham , Stark Elena , Dong Hongwei , Toga Arthur , Vinters Harry , Wisco Jonathan 
Published: June 2021

Alzheimer's disease (AD) is becoming more prevalent in an aging society, and numerous efforts have been devoted to learning about the disease. Consecutive sections of the hippocampus, entorhinal cortex, and frontal lobe regions from brains diagnosed with AD were stained for non‐heme iron (Fe) using a peroxidase enhanced Perl's stain, and for amyloid beta‐40 (Aβ‐40) and tau protein (tau) using an immunohistochemistry stain. We compared the qualitative spatial correlation between Fe, Aβ‐40, and tau deposits from images of the tissue. We determined that in human AD temporal lobe sections, Fe corresponded with Aβ‐40 depositions and heavy tau protein depositions. In sections from the hippocampus and entorhinal cortex region we found a correlation between Fe and Aβ‐40, but little correlation between Fe and tau depositions. The correlations found in the temporal lobe section suggests that one potential cause of AD is related to the build‐up Fe, Aβ‐40, and tau as well as Fe and Aβ‐40 in the hippocampus and entorhinal cortex.Grant Funding Source: NIH/NIA 1 R21 AG037843‐02, NIH/NCRR P41 RR013642‐12S1, Translational Research Fund (UCLA), and the McGinty Family Foundation
Regulation of NFkB‐dependent Interleukin‐8 in Human Macrophages By Nuclear IkBa and Proteasome Inhibition
Authors: Sanacora Shannon , Manna Subrata , Singha Bipradeb , Chang Tzu‐Pei , Ramaswami Sitharam , Vancurova Ivana 
Published: June 2021

Transcription of NFkB‐dependent genes is regulated by the nuclear translocation and accumulation of IkBa. In the nucleus, IkBa suppresses transcription of NFkB‐dependent pro‐inflammatory and anti‐apoptotic genes providing potential therapeutic targets. Post‐induction repression in stimulated cells, inhibition of the CRM1‐ dependent nuclear IkBa export by leptomycin B (LMB), and the inhibition of the 26S proteasome have all been found to induce nuclear IkBa accumulation. However, studies from our laboratory have shown that the inhibition of NFkB‐dependent transcription by nuclear IkBa is promoter specific. Transcription is also dependent on the subunit composition of NFkB dimers and post‐translational modifications of the recruited NFkB proteins. In this study, we have investigated the mechanisms responsible for the regulation of gene expression of the NFkB‐dependent proinflammatory chemokine interleukin‐8 (IL‐8) by nuclear IkBa and proteasome inhibition in human macrophages. Our results show that a different mechanism regulates the NFkB‐dependent transcription of IL‐8 compared to other NFkB‐dependent proinflammatory and antiapoptotic cytokines, such as TNFa, IL‐1 and IL‐6. While both IL‐8 and TNFa promoters are occupied by p65/65 homodimers in LPS‐stimulated macrophages, TNFa expression is inhibited by the LMB‐induced nuclear IkBa and proteasome inhibitor bortezomib, yet the IL‐8 expression is not inhibited by the nuclear IkBa, and is significantly up‐regulated by bortezomib. In addition, while the p65 NFkB homodimers recruited to IL‐8 promoter are phosphorylated on S536, p65 NFkB recruited to TNFa promoter is not phosphorylated. Together, our data indicate that the S536 p65 phosphorylation plays a crucial role in the regulation of IL‐8 transcription by nuclear IkBa in human macrophages.*Funded by NIH grants GM079581 and AI085497 to IV.
A naturally variable residue in the S1 subsite of M1‐family aminopeptidases modulates catalytic properties and promotes functional specialization
Authors: Klemba Michael , Ragheb Daniel , Schubot Florian , Dalal Seema 
Published: June 2021

The objective of this study was to identify principles governing the substrate specificity of M1‐family aminopeptidases at the S1 subsite, which interacts with the sidechain of the first residue of peptide substrates. By sequence comparison, we identified a residue in the S1 subsite that is highly variable and hypothesized that changes in this residue modulate S1 specificity. To test this hypothesis, we generated a large number of mutants at this position in the aminopeptidase PfA‐M1 from Plasmodium falciparum and in PepN from Escherichia coli. The kinetic properties of each mutant were characterized using a panel of natural dipeptide substrates. These studies revealed a complex interplay between the identity of the variable S1 residue and the kinetic properties of the enzyme. A dramatic shift in substrate specificity favoring the straight‐chain P1 sidechains Arg, Lys and Met could be effected by changing the S1 residue to proline. Structural analysis revealed that the proline residue induced a 1.1 Å shift of the polypeptide backbone, which resulted in constriction of the cylindrical S1 subsite. Together, the biochemical and structural data suggest that variation of a residue of the S1 subsite can modulate the catalytic properties of M1‐family aminopeptidases and ultimately contribute to functional specialization.This work was supported by National Institutes of Health grant AI077638.
Decreased autophagic flux as a mechanism of glucose‐ and fatty acid‐induced dysfunction in human aortic endothelial cells
Authors: Weikel Karen Anne , Ido Yasuo , Ruderman Neil 
Published: June 2021

The mechanisms by which cellular stress influences autophagic flux in cardiovascular disease vary between tissues and cellular contexts. The cellular response to glucose and fatty acids is regulated by adenosine monophosphate‐activated protein kinase (AMPK), but whether AMPK influences the effects of hyperglycemia and hyperlipidemia on autophagy in endothelial cells remains to be established. In human aortic endothelial cells (HAECs), we evaluated the effects of glucose and fatty acids on endothelial dysfunction by measuring transcription of endothelial nitric oxide synthase, adhesion of THP‐1 monocytes, and cellular ATP levels. Autophagic flux was assessed based upon expression levels of p62 and LC3‐II. Compared to HAECs in non‐stressed conditions, HAECs exposed to elevated concentrations of glucose and palmitate had a smaller ATP/ADP ratio and showed increased adhesion of monocytes. Under these hyperglycemic and hyperlipidemic conditions, autophagic flux was also decreased. Activation of AMPK attenuated glucose‐ and palmitate‐induced changes in these parameters, and chemical induction of autophagic flux diminished glucose‐ and palmitate‐induced changes in ATP/ADP and monocyte adhesion. Up‐regulation of autophagic flux may be one way in which AMPK can ameliorate glucose‐ and palmitate‐induced dysfunction in HAECs.Research support was provided by NIH/NHLBI HL068758