bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of PAT proteins with cytoplasmic lipid droplets in mouse enterocytes
Authors: Lee Bonggi , Zhu Jiabin , Wolins Nathan E. , Cheng Ji‐Xin , Buhman Kimberly K. 
Published: June 2021

The process of dietary fat absorption (DFA) by the absorptive cells of the intestine, enterocytes, is important in regulating energy balance in whole animals. Recently, we found that enterocytes dynamically store triacylglycerols (TGs) in cytoplasmic lipid droplets (CLDs) during DFA. To further our understanding of the process of DFA and regulation of TG rich CLD synthesis and catabolism within enterocytes, we investigated the expression and localization of PAT protein family members in enterocytes of mice under acute and chronic dietary challenges. We found that adipophilin and TIP47 are the only PAT proteins expressed in mouse intestinal mucosa. In mice acutely and chronically challenged by dietary fat, we imaged the cellular localization of TIP47 and adipophilin using immunofluorescence in combination with Coherent anti‐Stokes Raman scattering microscopy (CARS) to image TG in CLDs We found that TIP47 is expressed in the cytoplasm under all conditions but only associates with CLDs after an acute challenge. Adipophilin, on the otherhand is only expressed and associated with CLDs in enterocytes of chronic high‐fat fed mice. These results suggest distinct roles for TIP47 and adipophilin in DFA and ultimately regulation of whole animal energy balance.Grant Funding SourcePurdue Research Foundation
Delayed lactogenesis and excess neonatal weight loss are common across ethnic and socioeconomic categories of primiparous women in northern California
Authors: Dewey Kathryn G , Nommsen‐Rivers Laurie , Cohen Roberta J , Chantry Caroline J. , Peerson Janet M 
Published: June 2021

We evaluated early lactation success in a multi‐ethnic cohort of 448 primiparas in Sacramento, CA. Key outcomes were sub‐optimal infant breastfeeding behavior (SIBB), onset of stage II lactogenesis >72 h postpartum (delayed OL) and excess neonatal weight loss (> 10% of birth weight by 70‐98 h). Prevalence of SIBB was 69% at 2‐46 h, 34% at 3‐4 d, and 24% at 1 wk of age, and did not differ by maternal ethnicity, age, income group or education. Delayed OL occurred in 42% of women (34% of African‐Americans, 40% of Hispanics, and 44% of non‐Hispanic whites and Asian‐Americans); it was more common in women > 30 y of age than in those < 30 y (56% vs. 37%, p=0.0004), and in those with some vs. no college education (47% vs. 36%, p=0.03). Excess neonatal weight loss (excluding infants who received > 60 mL of formula at 0‐48 h) occurred in 18% and was more common in infants of mothers with higher age (28% if > 30 y vs. 14% if < 30 y, p=0.01), income (22% vs. 12%, p=0.048) and education (22% vs. 10%, p=0.03); differences across ethnic groups were marginally significant (8% of African‐Americans, 11% of Hispanics, 18% of non‐Hispanic whites and 31% of Asian‐Americans; p=0.08). We conclude that early breastfeeding problems such as delayed OL have reached epidemic proportions in this population of primiparas, especially among women with greater age and education. Further analyses will explore the biological and behavioral underpinnings for these findings.Supported by a grant from the Department of Health and Human Services, Maternal Child Health Branch.
Serum 25‐hydroxyvitamin D as a determinant of multiple sclerosis outcome following a pediatric demyelinating event
Authors: Hanwell Heather Elaine Courtney , Vieth Reinhold , Bar‐Or Amit , Magalhaes Sandra , Sadovnick Dessa , Arnold Douglas , Banwell Brenda 
Published: June 2021

OverviewVitamin D has been implicated in risk of autoimmune diseases including multiple sclerosis (MS). Children presenting with initial acquired demyelinating syndromes (ADS) are at high risk of subsequent MS diagnosis and thus, provide an opportunity to explore vitamin D as a determinant of MS risk.ObjectiveWe sought to determine whether serum 25‐hydroxyvitamin D [25(OH)D] at pediatric ADS presentation is predictive of subsequent MS diagnosis.MethodsIncident ADS cases were enrolled in a national pediatric prospective study. Serum collected at baseline was analyzed for 25(OH)D. MS was defined as a relapse confirmed on clinical exam.ResultsOf the 137 children enrolled, 21 (15%) were diagnosed with MS after a mean of 9.5 ± 7.6 mos (±SD). Serum 25(OH)D at ADS presentation was lower in children diagnosed with MS (45.8 ± 20.4 nmol/L) versus those remaining free of relapses to date (62.6 ± 29.3 nmol/L; p = 0.003). Quartiles of serum 25(OH)D at presentation strongly predicted subsequent risk of MS diagnosis: 27% of children in the lowest serum 25(OH)D quartile (=35.7 nmol/L) developed MS, compared with only 6% of the children in the highest quartile (= 77.9 nmol/L; trend p = 0.012).ConclusionOur results are consistent with the hypothesis that vitamin D is protective against autoimmune disease. These findings justify clinical trials involving intervention with vitamin D as a means to prevent MS.Grant Funding SourceMultiple Sclerosis Scientific Research Foundation, Multiple Sclerosis Society of Canada, Canadian Institutes of Health Research
Comparable Dose‐Response Glucose Lowering Effect with Whole vs finely Ground, Novel Omega‐3 rich Grain Salba (Salvia Hispanica L) Baked into White Bread
Authors: Vuksan Vladimir , Dias Andre , Lee Amy , Jovanovski Elena , Rogovik Alex , Jenkins Alexandra 
Published: June 2021

ObjectiveOily grains such as flax, sesame and poppy are common additions to bakery products. To evaluate the effect of particle size on postprandial glycemia, whole or finely ground omega‐3 rich grain Salba was baked into white bread in a dose response study.MethodsUsing an acute randomized, double‐blind, crossover design, 13 healthy subjects (5M; 8F; BMI 26.3 ± 7.3kg/m2) received, on 8 different occasions, either 7, 15 or 24 g of whole or finely ground Salba baked into white bread cotaining 50g available carbohydrate or bread control given twice. Capillary blood was taken fasting and at 15, 30, 45, 60, 90 and 120 minutes after consumption.ResultsCompared to control, all treatments containing 7,15,or 24g of whole and ground Salba reduced blood glucose iAUC (p=0.03) by 20%, 28% and 35% respectively compared to control (p<0.05), in dose dependent fashion (slope = ‐1.2 ± 0.05). No differences in glucose responses were found between whole vs ground Salba at the same dose levels.ConclusionsAddition of either whole or finely ground Salba to white bread lowers postprandial glycemia equally in a dose‐dependent manner making this novel omega‐3 grain versatile for consumption. Baking whole Salba in bread may also extend shelf life by minimizing fat oxidation.
Alteration of the autophagy‐lysosomal system in models of Parkinson's disease
Authors: Pivtoraiko Violetta Nikolaevna , Schacka John , Roth Kevin 
Published: June 2021

In Parkinson's disease (PD), increasing evidence suggests that neuron death may be related to alterations in the autophagy‐lysosomal pathway (ALP). To further investigate the role of the ALP in neuron death regulation in PD models, differentiated SH‐SY5Y human neuroblastoma cells were treated with either chloroquine (CQ), known to induce autophagic neuronal death, morphologically defined by the aberrant accumulation of autophagic vacuoles (AVs) concomitant with markers of apoptosis and/or necrosis, or rotenone (Rt), a selective inhibitor of complex I of the mitochondrial electron transport chain. CQ induced AV accumulation and inhibited cathepsin D processing (lysosomal aspartic protease), suggesting a CQ‐induced compromise of the ALP. CQ promoted α‐synuclein aggregation, one of the principal hallmarks of PD, emphasizing the potential for altered lysosome function in PD. CQ‐induced an increase in caspase‐3‐like enzymatic activity. Rt‐induced cell death was also accompanied by AV accumulation and increased caspase‐3‐like enzymatic activity. However, pharmacological inhibition of caspase activity did not significantly attenuate CQ or Rt‐induced cell death. These observations suggest that alteration of the ALP may facilitate accumulation of aggregated protein and contribute to the induction of multiple types of neuron cell death in PD.This work was supported by NS57098, NS 47466, and NS35107
Retinoid signaling pathway protein alterations in patients with amyotrophic lateral sclerosis
Authors: Kolarcik Christi , Bowser Robert 
Published: June 2021

The mechanisms underlying the motor neuron (MN) degeneration that occurs with amyotrophic lateral sclerosis (ALS) are poorly understood. Multiple studies have described the differential expression of retinoid signaling components in ALS patients and transgenic animal models. We investigated this pathway in human lumbar spinal cord tissue of patients with sporadic (SALS) and familial (FALS) ALS as well as controls with immunohistochemistry, immunoblotting, co‐immunoprecipitation and DNA‐binding assays. In SALS MNs, cellular retinoic acid binding protein (CRABP)‐II, the protein responsible for facilitating nuclear receptor interactions, was concentrated to the nucleus while FALS and control MNs had a diffuse cytoplasmic pattern. Nuclear retinoic acid receptor (RAR) βexhibited increased immunoreactivity in MN nuclei of individuals with SALS although both controls and individuals with FALS lacked this nuclear immunostaining. For MNs with RARβ nuclear staining, activated caspase‐3 was negative. Our results indicate that retinoid signaling is altered in ALS. Differences with respect to RARβ suggest that retinoid signaling impacts only SALS and that this is a pro‐survival response.Research Support: NIH grant ES013469 (RB); NIH T32 EB001026 (CK); NIH T32 05 TL1 RR024155‐02 (CK)
Effect of soluble JAM‐C on leukocyte transmigration in models of ischemia/reperfusion injury
Authors: Colom Bartomeu , Scheiermann Christoph , Woodfin Abigail , Meda paolo , Patel Nimesh , Marrelli Allessandra , Pitzalis Costantino , Thiemermann Chris , Aurrands‐Lions Michel , Imhof Beat , Nourshargh Sussan 
Published: June 2021

Numerous in vitro studies have implicated the adhesion molecule JAM‐C in leukocyte transendothelial cell migration but the role of JAM‐C in leukocyte migration in vivo requires further investigations. Here we used soluble JAM‐C (sJAM‐C) as a blocker of JAM‐C‐mediated reactions to investigate the role of this molecule in leukocyte transmigration in vivo as induced by ischemia/reperfusion (I/R). The study employed a murine model of kidney I/R injury and investigated I/R‐induced leukocyte migration by intravital microscopy in mouse cremasteric venules. In the kidney model, mice were subjected to an acute bi‐lateral renal ischemia (30 min) followed by a 24hr reperfusion period after which kidneys were removed and PMN infiltration was quantified in tissue sections by immunohistochemistry. Kidneys subjected to I/R injury exhibited a significant PMN infiltration response as compared to sham‐operated kidneys (~22 fold increase) and mice pre‐treated with sJAM‐C (3mg/kg, i.v.) showed a significant reduction in PMN infiltration (49.6% inhibition, p<0.05). In cremasteric venules, sJAM‐C suppressed I/R‐induced (30min ischemia/120 min reperfusion) leukocyte adhesion and transmigration. The results demonstrate a role for JAM‐C in PMN migration as induced by I/R injury.Funded by The Wellcome Trust and The British Heart Foundation.
Atorvastatin Attenuates Lrp5 Mediated Calcification in the Hypercholesterolemic Aortic Valves from ApoE mice
Authors: Kruger Bryan Mathew , Stock Stuart R , Rajamannan Nalini M 
Published: June 2021

BackgroundCalcification in the cardiovascular system is becoming an important prognostic marker for valvular disease. The cellular mechanisms of the calcification process are not well known.MethodsIn this study we tested the effect on lipids with and with atorvastatin in the ApoE mouse model to determine the localization of calcification and the regulation of the Lrp5 receptor in the valves. ApoE‐/‐ mice (n=60). Group I (n=20) normal diet, Group II (n=20) 0.25% chol diet (w/w), and Group III (n=20) 0.25% (w/w) chol diet+atorv for the development of calcification over 24 weeks. The aortic valve (AVA) was examined for calcification, Lrp5 and bone matrix markers. Bone formation was assessed by micro Computed Tomography (microCT), Lrp5, cbfa‐1 and osteopontin expression.ResultsThe cholesterol diet induced complex bone formations in the calcified AV with an increase in osteopontin, cbfa‐1 expression and Lrp5 receptor expression as compared to the Control(>3‐fold(p<05). Atorvastatin attenuated these markers. Echocardiography demonstrated a mild increase in the peak jet velocity across the aortic valve but not statisically significant.ConclusionThese results demonstrate that Lrp5 mediated bone formation in the hypercholesterolemic aortic valves is attenuated with atorvastatin. Providing evidence in that statins play a role in the treatment of this disease.
Interaction between Rgs and the Wnt Signaling Network during Zebrafish Organogenesis
Authors: Freisinger Christina M , Griesbach Hilary L , Lin Shengda , Slusarski Diane C 
Published: June 2021

We have identified calcium release as an output of Wnt signaling network and are investigating the mechanisms and context by which this Wnt signal mediates its biological effect on the developing embryo. We have determined that the early calcium transients are, in part, modulated by Wnt5 and require G‐protein signaling. To identify potential intracellular regulators of calcium release dynamics, we are characterizing members of the Regulators of G‐protein Signaling (RGS) protein family.We performed a comprehensive analysis of the role of RGS proteins utilizing the experimentally amenable zebrafish (Danio rerio). We cloned and characterized the expression pattern of rgs3, 4, and 5 and determined the developmental consequences of loss‐of‐function by gene knockdown studies. Developmental defects were identified by morphology, marker gene expression analyses and alteration to vascular outgrowth in transgenic zebrafish lines.One RGS family member is co‐expressed in similar tissues as Wnt5. Preliminary analyses suggest synergistic interaction. Structural/functional analyses were performed to determine if direct binding to Gα subunits is required for RGS developmental actions. To this end, we evaluated the ability of wild‐type and mutant RGS cDNAs to rescue knockdown phenotypes. We also evaluated the impact of RGS mis‐expression on calcium signaling in the embryo.Grant Funding SourceMarch of Dimes (5‐FY99‐806); NIH (RO3 HD045488‐01), RO1 (GM067881‐01); and American Heart Association Predoctoral Fellowship
Tissue engineering of an artificial nerve for injury repair
Authors: Terenghi Giorgio 
Published: June 2021

Currently peripheral nerve gap injuries are repaired with an autologous nerve graft, which provides regenerating axons with natural guidance channels, Schwann cells and extracellular matrix molecules. Biocompatible nerve conduits are an alternative for nerve reconstruction, as their surface micro‐geometry may be combined with cultured cells, growth factors and extracellular matrix molecules (ECM) to form a tissue engineered artificial nerve.The addition of cultured Schwann cells within the conduit has proved to have a crucial role, and we have been able to demonstrate their active participation in the regenerative process. Further improvements are provided by coating the conduits with ECM, which increase Schwann cells proliferation and axonal regeneration.More recently, we have been able to differentiate adult bone marrow mesenchymal stem cells towards expressing phenotypic and functional characteristics of Schwann cells, and their transplantation in bioengineered nerve conduits has proved beneficial in promoting enhanced nerve regeneration. We have also demonstrated similar differentiation capacity for adipose tissue derived stem cells, which offer a tremendous potential for clinical application due to their easy accessibility. These results indicate that a bioengineering nerve implant is becoming closer to clinical reality.
A Complex Involved in the DNA Damage Response Network of Fanconi Anemia and Breast Cancer
Authors: Yan Zhijiang , Xu Dongyi , Guo Rong , Xue Yutong , Ling Chen , Li Yongjiang , Wang Weidong 
Published: June 2021

Fanconi anemia (FA) has recently become an attractive model to study breast cancer susceptibility (BRCA) genes, as three FA genes, FANCD1, FANCN, and FANCJ, are found to be identical to BRCA genes BRCA2, PALB2, and BRIP1. Thirteen FA proteins have been identified, and they function in a DNA damage response network consisting of ATR, BLM, and BRCA1.Our group has purified the FA core complex, and shown that it contains 8 FA proteins, together with two new FA‐associated polypeptides, FAAP100 and FAAP24. This complex contains FANCL, an ubiquitin ligase essential for monoubiquitination of FANCD2 and FANCI. It also contains FANCM, an enzyme capable of translocating and remodeling branched DNA structures, such as replication forks and recombination intermediates.We have also purified the BLM helicase complex, and found that it contains two novel proteins, named RMI1 and RMI2. The latter two proteins constitute a novel OB‐fold complex which is essential for BLM to suppress sister‐chromatid exchange. Interestingly, the FA core complex and BLM complex constitute a larger multiprotein complex, termed BRAFT (for BLM, RPA, FA, and Topoisomerase IIIƒÑ). The fact that FA and BLM proteins are in the same complex suggests that they work together in a genome maintenance pathway.
Targeted and Pharmacologic Inhibition of DNMT3b Sensitizes Breast Cancer Cells to Chemotherapy
Authors: Sandhu Rupninder , Roll J Devon , Rivenbark Ashley G , Coleman William B 
Published: June 2021

Many basal breast cancers express a hypermethylation defect related to DNMT3b overexpression. This feature may contribute to chemotherapeutic resistance and provides a target for development of new treatment strategies. To determine the influence of DNMT3b status on the sensitivity of hypermethylator breast cancer cells (MDA‐MB‐453) to doxorubicin hydrochloride (DOX), we studied the effects of RNAi‐mediated DNMT3b knockdown (KD) and/or demethylating agent 5‐aza. RNAi‐mediated DNMT3b KD increases the effectiveness of DOX, reducing the IC50 from 0.07 µM to 0.049 µM and increasing cell kill by 16% in response to 0.06 µM DOX. Pretreatment of cells with 250 nM 5‐aza for 3d and 7d or 500 nM 5‐aza for 3d did not increase DOX sensitivity. However, 7d pretreatment with 500 nM 5‐aza sensitized cells by reducing the IC50 to 0.039 µM and increased cell kill by 29% at 0.06 µM DOX. 5‐aza treatment of KD cells reduced IC50 to 0.038 µM and increased cell kill by 27% at 0.06 µM DOX. These results show: (i) RNAi‐mediated DNMT3b KD sensitizes hypermethylator breast cancer cells to DOX, (ii) 5‐aza treatment sensitizes hypermethylator cells to DOX as a function of dose and duration of exposure, and (iii) DNMT3b KD and 5‐aza treatment increase the effectiveness of DOX, individually and in combination. These results strongly suggest that targeting DNMT3b can be exploited to improve the efficacy of breast cancer chemotherapy.Support: NIH CA78343
Surgical anatomy of the male pelvis: a 3D model based on the Visible Human Project®
Authors: Sanchez Jaime E , Krieger Beth R , Marcet Jorge E , Decker Summer J , Ford Jonathan M , Hilbelink Don R 
Published: June 2021

Surgical anatomy of the pelvis remains a complex and often controversial topic. Operating in the pelvis can be difficult due to poor visualization, limited maneuverability, and ill‐defined surgical anatomy. However, proper identification and preservation of pelvic autonomic nerves in surgery is associated with decreased morbidity including reduced urinary and sexual dysfunction.The objective of this study was to construct an accurate 3D computer model of the surgical anatomy of the male pelvis, with particular focus on fascias and the autonomic nervous system.The model was created by meticulous segmentation of the Visible Human Project® male data set and enhanced with findings obtained from cadaveric dissections and pelvic operations. Specific attention was paid to identification of fascial planes and the course of autonomic nerves. The model was rendered in the 3D visualization software packages, Mimics v. 12, OsiriX v. 3, and 3ds Max 9. It was then compared to cadaveric dissections and operative findings for accuracy.We conclude that it is possible to minimize autonomic morbidity in the pelvis by proper identification of fascial planes and have constructed an enhanced 3D model of the male pelvis based on the Visible Human Project®. This model serves to improve anatomic understanding for surgeons and provides the most detailed 3D rendering of an actual human pelvis for further study.Grant Funding SourceNone
Mechanical and chemical activation of muscle satellite cells is perturbed in normal aged mice
Authors: Leiter Jeff , Anderson Judy 
Published: June 2021

Age‐related muscle atrophy and the importance of satellite cells in muscle maintenance, growth and repair led us to examine the effects of mechanical stretch, nitric oxide (NO), and age on satellite cell (SC) activation and gene expression in normal young and old mice. Baseline variables (body mass, muscle mass, fiber cross‐sectional area (CSA), muscle strength, SC population, stretch activation and gene expression) were obtained from normal C57/BL6 mice at 3, 6, 8, 12 and 18 months‐of‐age. Activation was assayed by 3H‐thymidine incorporation into extensor digitorum longus (EDL) muscles isolated for culture with (S) or without stretching (US). In a second experiment, muscle from 8‐ and 18‐month old mice was treated with one or more of: stretch, L‐Arginine (LA); NO‐donors (isosorbide dinitrate (ISDN) and MyoNovin (MN) a new formulation); Nω‐nitro‐L‐Arginine methyl ester (LN). EDL muscles from 6‐month‐old mice required a greater stretch stimulus (20% vs. 10% length increase) than EDL from younger mice to increase SC activation. Stretch did not increase SC activation in mice older than 6 months‐of‐age. NO from either endogenous (LA) or exogenous (ISDN, MN) NO donors increased SC activation by stretch in 8‐ but not 18‐mo‐old EDLs. Perturbed sensitivity to mechanical stimulation and NO in 18‐mo‐old mice may partly explain loss of muscle mass, fiber CSA, relative grip strength and SC pool size with age. Similar to dystrophic muscle, a disrupted dystrophin‐glycoprotein complex and subsequent alteration in NO availability may affect the ability of native satellite cells to maintain or effectively regenerate aged muscle.Grant Funding SourceCanadian Space Agency Life Sciences