bluuebunny/crossref_metadata_2025_split huggingface dataset:
Subregions of the inferior parietal lobule are associated with progression to Alzheimer's disease in participants of the Alzheimer's Disease Neuroimaging Initiative
Authors: Greene Sarah Judith , Killiany Ronald 
Published: June 2021

Several regions within the brain have been associated with progression from normal to Alzheimer's disease (AD) based on magnetic resonance imaging (MRI) studies, including the hippocampus, entorhinal cortex, and more recently, the inferior parietal lobule (IPL). In this study, the IPL was divided into three regions: the gyrus (G‐IPL), the banks of the sulcus (B‐IPL), and the fundus (F‐IPL) to determine if these regions were associated with the progression from normal to AD. Participants of the ADNI (n=12, 50% male, average age 78) underwent a structural MRI scan and neuropsychological exam (NP), and were categorized as normal controls, mild cognitively impaired (MCI), or AD. FreeSurfer was used to measure these regions. Once scans were processed, each IPL region was manually traced based on automated curvature intensities and corrected for head size. Multivariate analysis of variance determined that the B‐IPL was different among groups (p<0.05) in the right (RH) and left (LH) hemisphere, and G‐IPL was different in the LH. Correlations between these regions and NP scores were as follows (p<0.05): LH B‐IPL with Auditory Verbal Learning immediate and delayed, and both LH and RH G‐IPL with the categories test. These findings suggest that the banks and gyral portions of the IPL are impacted by AD pathology before the fundus of the IPL in individuals with MCI and AD.Grant Funding SourceNone
Regulation of DNA damage responses by the polymerase manager proteins UmuD and UmuD′
Authors: Beuning Penny J , Sefcikova Jana , Fang Jing Susan , Engen John R 
Published: June 2021

Organisms experience DNA damage from numerous sources. When bacterial cells experience DNA damage and other stresses, the SOS response is induced, leading to upregulation of at least 50 genes in E. coli. Among the upregulated genes are specialized Y family DNA polymerases, which replicate damaged DNA and play a role in tolerance to DNA damage. The activity of these potentially mutagenic proteins is tightly regulated. The manager proteins UmuD2 and the cleaved form UmuD'2 provide one regulatory mechanism. The umuD gene products interact with both Y family polymerases, the replicative DNA polymerase, and the beta processivity clamp. The goal of this study is to determine how the conformation and dynamics of the umuD gene products regulate the cellular response to DNA damage. We are characterizing the effects of UmuD and UmuD' on DNA polymerase III activity and probing their conformations using fluorescence resonance energy transfer (FRET) and hydrogen‐deuterium exchange mass spectrometry (HXMS). In HXMS experiments, backbone amide hydrogens that are solvent‐accessible exchange with deuterium over time, whereas inaccessible hydrogens do not exchange. Our HXMS results reveal that the N‐terminal arm of UmuD, which is not present in the cleaved form UmuD′, exhibits local partial unfolding. Additionally, there are substantial regions of stable conformation in both proteins.This work is funded by a Dreyfus Foundation New Faculty Award.
Association of Sets of Alleles of Gene Encoding Lipoprotein Lipase Enzyme With Type 2 DM and Its Macrovascular Complications
Authors: Hemimi Neveen Salah El Din , Abd El Salam Mona Mohamed , Abd Elwahab Mahmoud A 
Published: June 2021

BackgroundLipoprotein Lipase (LPL) increases the uptake and catabolism of triglycerides rich lipoproteins (TRLs) by hydrolyzing triglycerides in chylomicrons and VLDLs and also by serving as a bridge mediating the binding of TRLs to cell surface via heparan sulphate proteoglycans leading to their uptake by a variety of receptors.AimTo detertmine whether two LPL polymorphism (LPL Hind III and LPL S447X) can be considered as predictors for DM and its macrovascular complication.Methods176 normal individual, 42 non‐complicated type 2 diabetic patients and 78 macrovascular complicated type 2 diabetic patients were enrolled in the study. The LPL Hind III and LPL S447X genotypes were identified by RFLP‐PCR of peripheral blood DNA samples. Analysis of data was done by using SPSS program.ResultsAllele frequencies for H+ and S were 80.8% and 93.3% respectively in the diabetic group compared to 64.2% and 90.9% in the control group. The carriers of either (H+/H+) or (SS) variant of LPL were at high risk of developing type 2 DM (OR= 2.6; 95% CI= 1.6‐4.3 and OR= 1.4; 95% CI= 0.7‐2.7) respectively. Furthermore they were at much higher risk of developing macrovascular complications (OR= 3.7; 95% CI= 1.6‐8.2 and OR= 3.3; 95% CI =1.1‐10.0) for carrier of (H+/H+) and (SS) genotype respectively.Conclusion(H+/H+) and /or (SS) genotype were associated with Type 2 DM and its macrovasular complications.Source of research supportDubai Medical College for Girls
Genetic Polymorphism of Ectoenzyme Nucleotide Pyrophosphate Phosphodiesterase (ENPP1) and Susceptibility to Type 2 DM and Its Complications
Authors: Hemimi Neveen Salah El Din , Abd El Salam Mona Mahmoud , Abd Elwahab Mahmoud A 
Published: June 2021

BackgroundA functional missense DNA polymorphism in exon 4 of ENPP1 gene causes amino acid change from lysine to glutamine at codon 121 (K121Q). The Q variant of PC1 is associated with reduction of insulin receptor autophosphorylation and therefore a stronger inhibitor of insulin signaling.AimTo test the hypothesis that ENPP1 K121Q polymorphism is associated with type 2 DM and its complication.Methods167 normal individual, 30 non‐complicated type 2 diabetic patients and 76 complicated type 2 diabetic patients were enrolled in the study. The ENPP1 K121Q genotypes were identified by RFLP‐PCR of peripheral blood DNA samples. Analysis of data was done by using SPSS program.ResultsAllele frequency for Q was 36.8% in the diabetic group compared to 26% in the control group. The carriers of XQ genotype (KQ and QQ) were at high risk of developing type 2 DM (OR= 1.8; 95% CI = 1.1‐2.9) when compared with the carrier of KK genotype. Furthermore they were at much higher risk of developing its complications (OR= 2.1; 95% CI=0.9‐4.9).ConclusionQ 121 allele is a genetic determinant of type 2 DM and related atherogenic phenotypes.Source of research supportDubai Medical College for Girls
IDENTIFICATION OF PROTEINS OF VIGNA SUBTERRANEA L.VERDC (FABACEA)
Authors: Okpuzor Joy , Ogbunugafor Henrietta A. , Okafor Uzoma , Sofidiya Magarette O. 
Published: June 2021

This study attempts to highlight the importance of Bambara groundnut, a legume as a booster of the dietary protein stock available to the lower strata of the population in most developing countries especcially in African as well as suspected health benefits of some of the proteins in the management of cardiovascular diseases, diabetes, digestive tract disorders and weight control.The indentification of the proteins of Vigna subterrenea L. Verdc. was carried out using MudPit and LC‐MALDI TOF‐TOF mass spectrometry. Some of the proteins we isolated include Seed storage protein B, Mung bean seed albumin Chain A, Crystal Structure Of Adzuki Bean 7s Globulin‐3, Dehydrin and 8S globulin alpha subunit. We also observed the sequence homology of most of the proteins with those of some other Vigna species, especially Vigna radiata, Vigna angularis and Vigna unguiculata. Our overall goal is to direct attention to Bambara groundnut and cause it to be removed from the list of under‐utilized and neglected crops and initiate a shift in governmental policies towards this direction.
A 31P‐NMR Study to Determine the Percent Composition of Aqueous Dispersion of Soy Lecithin
Authors: Liotta Marcus Toland , Amburgey‐Peters Judith C. , Peters Scott 
Published: June 2021

Phospholipids are organic compounds that are comprised of a glycerol backbone, two fatty acid acyl‐chains, and a phosphate head group with various substituents. In an aqueous environment, the hydrophobic acyl‐chains minimize their contact with water by aligning to form a bi‐layered system. As the bi‐layer converges upon itself, stable bi‐layered spheres, liposomes, form. Liposomes have been used for years as a delivery agent for medical and commercial applications. In the commercial field, soy lecithin is typically used as the mixed phospholipid source to prepare liposomes. However, the concentrations of the different phospholipids can vary between providers and batches.31P NMR is to be sensitive enough to differentiate each of the specific phospholipids found in the soy lecithin mixture. Deuterated Chloroform (CDCl3) and Methanol (CH3OH) were used as the solvent system, with a mixture of Cesuim‐Ethylenediaminetetraacetic acid (Cs‐EDTA) added to further separate the signals. An internal standard of Triethyl phosphate (TEP) was used to quantify the individual concentrations of phospholipids. Utilizing 31P‐NMR, it is possible to analyze the phospholipid content of liposomes and follow the degradation of the phospholipids over time and under various conditions. This research was made possible by funding from Ingredient Innovations International and the Chemistry Department of Chemistry at The College of Wooster.
Role of N‐glycans of the β2 subunit in assembly and trafficking of the α1β2 Na,K‐ATPase
Authors: Vagin Olga , Tokhtaeva Elmira , Sachs George 
Published: June 2021

The non‐glycosylated αsubunit of the Na,K‐ATPase is unable to exit the ER unless it is co‐expressed with the N‐glycosylated ? subunit. We tested whether N‐glycans of the ?2 subunit are required for proper folding, assembly and quality control of the Na,K‐ATPase in the ER. The over‐expressed ?2 subunit was co‐localized with the endogenous α1 and ?1 subunits in the plasma membrane of MDCK cells and co‐immunoprecipitated with the α1 subunit from cell lysates. A minor fraction of the ?2 subunit was detected in the ER without the α1 subunit. The ?2 subunit, but not the α1 subunit, was co‐immunoprecipitated with the ER chaperone, calnexin. Mutation of more than three of the eight N‐glycosylation sites of the ?2 subunit prevented α1 ?2 assembly, augmented association of the ?2 subunit with calnexin, and resulted in complete retention of the ?2 subunit in the ER. In contrast, the endogenous α1 subunit was neither associated with calnexin nor retained in the ER. Thus, particular N‐glycans are required for calnexin‐mediated folding and quality control of the unassembled ?2 subunit, but not of the α1 ?2 complex. The proper folding of the ?2 subunit is a prerequisite for the α1 ?2 assembly, which, in turn, is necessary for the export of the ?2 subunit from the ER to the Golgi. Therefore, neither the α1 nor the β2 subunits are able to exit the ER unless they are assembled in the full enzyme.Supported by NIH, DK077149 and DK58333.
Membrane bound prenylated C17orf37 is a critical regulator of cancer cell migration and invasion
Authors: Dasgupta Subhamoy , Gryczynski Zygmunt , Vishwanatha Jamboor K 
Published: June 2021

C17orf37 is located in the hot spot locus of human chromosomal region 17q12‐21 next to ErbB2. Previously we have shown that C17orf37 expression is significantly higher in prostate cancer cells and tissue specimens compared to normal prostate cells. By gene knock down studies, we demonstrated that C17orf37 regulates prostate cancer cell migration and invasion by modulating key proteins involved in these processes, such as MMP‐9, uPA and VEGF. The migration‐defect phenotype in C17orf37 depleted prostate cancer cells were restored on C17orf37 overexpression, with concomitant increased expression of MMP‐9, uPA and VEGF proteins. Knockdown of C17orf37 abolished p‐Akt and reduced DNA binding activity of NF‐κB. Cellular localization studies using confocal and TIRF microscopy demonstrated predominant expression of C17orf37 protein in the membrane. C17orf37 protein has a C‐terminal prenylation motif 'CVIL' and using inhibitors of prenyl transferase enzymes we demonstrate that C17orf37 is preferentially geranylgeranylated by GGTase‐1 enzyme and this inhibition results in reduced membrane bound C17orf37. We identified annexin A2 as a novel interactor of C17orf37 and by FLIM based FRET assay we found that these two molecules physically interact at the membrane region. Our studies show C17orf37‐annexin A2 interaction is critical for tumor cell migration and invasion, by regulating downstream signaling molecules.(Supported grants from the National Institutes of Health CA109593 and MD 001633)
Discovery of novel peptide hormones using prohormone convertase screening
Authors: Ozawa Akihiko , Lee Ernestine , Hoshino Akina , Halenbeck Robert , Kothakota Srinivas , Lindberg Iris 
Published: June 2021

Bioactive peptides play critical roles in diverse biological phenomena; the discovery of novel peptides thus has the potential to open entirely new fields of research. The successful sequencing of entire genomes of various organisms has yielded numerous novel candidate precursor genes; however, the identification of novel bioactive peptides from such genomic information has been hampered by their small size. In this study, we attempt to identify novel peptides using a combinatorial screening approach: a predictive algorithm followed by "restriction protease" screening.The algorithm was trained using various properties associated with known peptide precursors. Approximately 150 genes were identified as coding for candidate peptide precursors.In a preliminary screening, 21 genes were chosen from this list and expressed in tagged form in HEK293 cells. Proteolysis using prohormone convertases 1 and 2 and furin was performed in order to confirm cleavage of expressed proteins. Sixteen of 21 precursors were cleaved by one or more convertases; 5 proteins were not cleaved and may represent false bioinformatics hits. In situ hybridization of mouse brain with antisense cDNA from a cleaved precursor indicated limited expression within the mediobasal hypothalamus. These results demonstrate that our bioinformatics/convertase screening approach is a promising method for peptide hormone discovery. (DA05984)
Calcium restriction inhibits cancer cell proliferation in vitro
Authors: Sridhar Rajagopalan , Cousins Valerie Marie , Zhang Renshu , Zhou Yanfei , Haddad Georges , Ashayeri Ebrahim 
Published: June 2021

Prostate and breast cancer cells metastasize to the bone. Strontium‐89 (Sr‐89) is a radioisotope that is used for treating bone metastases. The effect of strontium on calcium uptake was studied in human fetal osteoblast (hFOB) as well as androgen independent PC‐3 human prostate and MDA‐MB231 human breast cancer cells using digitized fluorescence microscopy in cells preloaded with Fura‐2AM. The effect of calcium deprivation on cell growth was studied using the MTT assay. When compared to cultures grown in complete medium, calcium and serum deprivation for 24 hours decreased cell growth by 80, 58 and 52 percent in hFOB, MDA‐MB231 and PC‐3 cells respectively. Addition of strontium chloride (up to 2 mM) did not cause further growth inhibition in calcium and serum starved medium. Calcium deprivation caused a G1 block and decreased the proportion of cells in the S phase. PC‐3 cells cultured for 24 hours in complete calcium containing medium supplemented with fetal bovine serum had a cell cycle distribution of 56% G1, 18.4% G2 and 25.6% S phase cells. These parameters shifted to 74.5% G1, 12.8% G2 and 12.6 % S phase cells in calcium and serum starved medium. Although strontium did not affect cell growth, it inhibited uptake of calcium by PC‐3 and MDA‐MB231 cells. Uptake of calcium from the medium by cells was inhibited by the anti diarrhea drug loperamide, which is a calcium channel blocker. Interestingly, loperamide inhibited hFOB and MDA‐MB231 cell growth even in complete medium. Preferential inhibition of calcium uptake by cancer cells may be an option in cancer therapy.(Supported in part by USMRMC grants DAMD17‐03‐1‐0759, DAMD17‐03‐1‐0123, 2 G12 RR003048 from RCMI, NCRR, NIH and R 25HL003679 from HLBI, NIH)
Alpha ‐ linolenic acid (ALA)‐ rich flaxseed oil (FO) enhances the effectiveness of trastuzumab (TRAS) in reducing the growth of HER2 overexpressing human breast cancer tumors (BT‐474)
Authors: Mason Julie Kathleen , Truan Jennifer S , Thompson Lilian U , Chen Jianmin 
Published: June 2021

TRAS is the primary drug for breast tumors that overexpress epidermal growth factor receptor 2 (HER2) but tumors develop resistance within 1 year of treatment. Our objective is to determine whether combining dietary ALA‐rich FO with TRAS treatment will enhance TRAS effectiveness. HER2 overexpressing breast tumor cells (BT‐474) were tested for proliferation and HER2 level in vitro after treatment with ALA (50µM), TRAS (10µg/ml) or their combination. Compared with untreated control, ALA, TRAS and combination caused a 35%, 54% and 61% reduction in proliferation and a 23% increase and 19% and 88% reduction in HER 2 expression (p<0.05), respectively. Ovariectomized mice with BT‐474 tumors were fed the basal diet (BD) (control) or treated with TRAS (2.5 or 5mg/kg) and fed either the BD or BD supplemented with 8% FO for 4 weeks. Compared to control, both TRAS and FO+TRAS treatments caused significant reductions in tumor growth over time (P<0.05). Control tumors increased in size by 63% while tumor size with FO+TRAS2.5 was reduced by 85% which is greater than that with TRAS2.5 (16%) (p<0.05) and not significantly different from that with TRAS5, alone or with FO. FO+TRAS2.5 caused greater reduction ( 85%) in cell proliferation (Ki67 labeling index) than with TRAS2.5 alone (59%; p<0.05). In conclusion, ALA and ALA‐rich FO enhanced TRAS effects and combined FO and low dose TRAS was just as effective as high dose TRAS.Grant Funding SourceNSERC
Efficacy of curcumin in lung cancer hamster model
Authors: Geamanu Andreea , Goja Arvind , Zaheeruddin Shaistha , Gupta Smiti 
Published: June 2021

Curcumin, the polyphenolic pigment from the rhizome Curcuma longa, is known for its antioxidant, anti‐inflammatory, antibacterial, and recently, anticarcinogenic properties. The aim of this study was to investigate efficacy of curcumin in lung cancer induced hamster model. 32 male Golden Syrian hamsters were divided into test (TO, T2 n= 10 each) and control (CO, C2 n=6 each) groups. Test groups received BOP (N‐nitrosobis (2‐oxopropyl) amine; 10mg/kg), a carcinogen, for 12 weeks, while the control animals received saline injections. Effect of curcumin was examined by providing 0 (C0, T0) or 2% (C2, T2) dietary curcumin. After 24 weeks tissues were harvested and lungs fixed for H&E and AE1/AE3 immunohistochemistry staining. COX‐2 and COMET assays were performed to determine the degree of inflammation and DNA damage in the tissues respectively. Histology showed significant differences in cancer development between the treatment groups with (T2) and without (T0) curcumin intervention. Cancer incidence (11.1% (T2) vs 45.5 %(T0)) and survival rate (72% (T2) vs. 33% (T0)) were significantly different. Loss in body weight, increase in Cox‐2 levels and DNA damage reinforced the beneficial role of curcumin in decreasing lung cancer in the hamster model. Overall, the study shows the chemopreventive effect of curcumin. Further investigations are needed to test curcumin as a therapeutic agent in the human population.Grant Funding SourceWayne State University
A fish oil/pectin diet suppresses radiation‐enhanced colon carcinogenesis via down‐regulation of the β‐catenin signaling pathway
Authors: Kim Hyemee , Turner Nancy D. , Taddeo Stella S. , Davidson Laurie A. , Wang Naisyin , Vannucci Marina , Chapkin Robert S. , Carroll Raymond J. , Lupton Joanne R. 
Published: June 2021

In our previous study, a fish oil/pectin (FP) diet protected against radiation‐enhanced colon carcinogenesis by maintaining an elevated level of apoptosis relative to a corn oil/cellulose (CC) diet. The goal of this study was to determine the differences between the protective and promotive diets in the patterns of gene expression measured in exfoliated colonocytes from rats exposed to radiation (+/‐ 1 Gy, 1 GeV/nucleon Fe ions) and a chemical carcinogen (AOM, 2x, 15 mg/kg BW). Microarray data were analyzed using a mixed model ANOVA procedure, and genes exhibiting differential expression underwent Gene Ontology (GO) enrichment analyses. Radiation treatment affected expression of genes within the Wnt/β‐catenin pathways, which are involved in cell proliferation and apoptosis. FP feeding reduced expression of tyrosine kinase related genes, which are regulators of the Ras‐PI3K/Akt signaling pathway. Therefore, a FP containing diet may suppress β‐catenin signaling induced by the radiation treatment, thereby contributing to the maintenance of apoptosis.Grant Funding SourceSupported by NSBRI (NASA NCC 9‐58) and NIH (CA57030 and CA59034).
Nutritional status and intake post nutritional supplementation in prostate cancer patients undergoing radiotherapy
Authors: Bartalone Rachel Leigh , Tyrpak Donna , Browne Richard W. , Wilding Gregory E. , Horvath Peter J. , Brown Jean K. 
Published: June 2021

Patients undergoing radiation therapy show decreased appetite, declining nutritional intake and status. The use of dietary supplementation during therapy has been questioned. To examine this effect, 53 prostate cancer patients were assigned to 3 groups (Placebo, DRI ‐ Dietary Reference Intake levels of vitamins/minerals, or OM ‐ Orthomolecular levels of antioxidants were added to DRI ‐Vitamin C, E, Se, and Carotenoids). Blood, body measures, and 3 day diet/activity records were collected at baseline and 3 times during supplementation ‐ before, during, post therapy. Energy imbalance increased with Placebo due to increasing energy expenditure and decreasing energy intake (from a decrease in carbohydrate and sugar intake), but not with DRI and OM. Before supplementation, micronutrient intake was generally below DRI levels and stayed low with Placebo. After DRI and OM, 95% of subjects reached DRI intakes, except Vitamin D and A (50 and 75%, respectively). Only plasma vitamin C increased with DRI. After OM; plasma vitamin C, alpha‐tocopherol, beta‐carotene and lycopene increased (80, 110, 160, and 40%, respectively), while lutein did not increase significantly. Energy balance was more negative over therapy without supplementation, due to increased activity and a decreased carbohydrate intake. The negative energy balance increase may be due to lack of micronutrient intake combined with radiation therapy.Grant Funding SourceNCI/NIH 5R21CA102391‐2
Differences in body composition and metabolism in stunted compared to normal height children in Jamaica.
Authors: Pilewski Kathryn , Soares‐Wynter Suzanne , Walker Susan , Hoffman Daniel 
Published: June 2021

While the prevalence of undernutrition is decreasing worldwide, there is still a large number of undernourished children in many developing countries. Previous research has shown that stunted children are more likely to have impaired fat oxidation and greater fat mass following recovery and later in life. However, it is not clear what metabolic differences exist prior to recovery from undernutrition. Thus, we measured body composition (using anthropometry) and energy metabolism (using indirect calorimetry) in 102 stunted and normal height children living in Jamaica.The children were split into stunted (< ‐2 HAZ) or control ( HAZ > ‐1 groups), both of whom had similar WHZ (‐0.68 ± 0.82 v ‐0.37 ± 0.76 kg). Differences between the groups were analyzed using Student's t‐Test and ANOVA. The stunted group had significantly lower fat mass (3.56 ± 0.89 v 4.58 ± 1.33 kg) and were older (7.86 ± 0.36 yrs v 6.83 ± 1.13 yrs) compared to the control group. REE was significantly lower in the stunted group compared to the control group (1118 ± 134 v 1323 ± 165 kcal/day), even when adjusted for lean body mass and sex (1168 ± 24 v 1298 ± 16 kcal/day). There were no significant differences in the respiratory quotient between the groups (0.83 ± 0.05 v 0.85 ± 0.05).Based on the data presented, we conclude that stunted children have lower metabolic rates, independent of lean body mass, compared to normal height children of similar weight for height.