bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of alcohol and alcohol‐metabolizing SNPs on serum vitamin D levels in postmenopausal women in a controlled feeding study
Authors: Mahabir Somdat , Baer David , Pfeiffer Ruth , Taylor Philip R. 
Published: June 2021

BackgroundAmong alcoholics vitamin D metabolism is altered and alcoholics have decreased vitamin D levels. However, no published data is available on the role of low to moderate alcohol consumption on vitamin D levels.ObjectiveThe objective of this study was to evaluate the effects of 8 weeks of no alcohol, low (1 drink or 15g/d) and moderate (2 drinks or 30g/d) alcohol consumption on serum 25(OH)D concentrations in postmenopausal women in a controlled feeding study and to assess whether alcohol metabolizing SNPs (ADH1B_02, ADH1B_05, ADH1C_01, ADH1C_02, ALDH2_07, CYP2E1_02, CYPE2_06, CYP2E1_07, CYP2E1_12, CYP2E1_13, CYP2E1_21, CYP2E1_22) modified the levels of 25(OH)D.DesignPostmenopausal women (n = 51) consumed 0, 1 drink, and 2 drinks of alcohol/day for 8 weeks as part of a controlled diet in a randomized crossover design. Fasting blood samples were drawn at baseline, at 4 weeks and at 8 weeks. Serum 25(OH)D concentrations were measured by ELISA. Wilcoxon rank sum and linear mixed models were used to compare differences in serum 25(OH)D concentrations from placebo to 1 and 2 drinks/day in the 8‐week samples.Results1 or 2 drinks/day for 8 weeks had no significant impact on serum 25(OH)D concentrations. We did not find any significant interactions between any of the SNPs and alcohol treatment on serum 25(OH)D concentrations.ConclusionThe data indicate that low to moderate alcohol consumption for 8 weeks had no significant impact on serum 25(OH)D concentrations among postmenopausal women in a tightly controlled feeding study.
Neonatal administration of monosodium glutamate (MSG) to induce Type‐2 diabetes in prepubertal pigs
Authors: Price Kathryn L. , Brown Lindsey A. , Wagner Ashley L. , Utt Matthew D. , Wankhade Umesh D. , Good Deborah J. , Escobar Jeffery 
Published: June 2021

Pigs were given 4 mg/g BW of MSG or saline (SAL) i.p. 0, 2, 4, 6, 8, and 10 d after birth. After overnight fasting, 3‐month‐old pigs consumed 2 g/kg BW of D‐glucose. Blood samples were collected 0, 60, and 120 min for plasma glucose (GLC) and insulin (INS) quantification. GLC (mg/dL) was not different (P=0.78 to 0.96) at 0 (SAL, 89.0±11.3; MSG 79.6±11.2) or 60 min (SAL, 179.4±11.3; MSG 194.6±11.2) between treatments. INS (μIU/mL) was not different (P=0.83 to 0.99) between treatments at 0 (SAL, 2.1±2.4; MSG, 1.4±2.8) or 60 min (SAL, 27.6±2.4; MSG 32.5±2.8). At 120 min, GLC was 44% greater (P=0.03) in MSG (121.8±11.2) compared to SAL (84.3±11.3) pigs. INS was 3.2‐fold greater (P=0.0002, ln transformed data) in MSG (7.3±2.8) compared to SAL (2.3±2.4) pigs. GLC‐to‐INS ratio was not different (P=0.99) at 0 or 60 min but was lower at 120 min (P=0.02) in MSG (26.9±4.6) compared to SAL (47.0±4.0) pigs. Collectively, these results indicate that neonatal administration of MSG leads to impaired oral glucose tolerance in prepubertal pigs, which implicates swine as a suitable animal model to study nutritional interventions in children with Type‐2 diabetes. Funding: Virginia Agricultural Experiment Station.Grant Funding Source: Virginia Agricultural Experiment Station
Nutrient Rich Food Options in Grocery Stores: Buying healthier foods without paying more
Authors: Mammarella Sarah , Colby Sarah E , Gross Kevin , Rivera David , Pawlak Roman 
Published: June 2021

ObjectiveThe objective of this research was to assess the price difference between nutrient rich and less nutrient rich paired food items in grocery stores.MethodsAll grocery stores in Greenville, NC (N=13) were assessed using a modified Nutrition Environment Measures Survey (NEMS).Outcomes MeasuredAll foods (n=126) with a nutrient rich and a less nutrient rich version were assessed for price difference.ResultsOf 63 food item pairs assessed, less nutrient rich food items never cost more than the more nutrient rich counterpart. The majority (52.4%) of the food item pairs were found to have no difference in price.ConclusionsIn grocery stores, many nutrient rich options can be purchased without increasing food expenditures.Grant Funding Source: None
Potential impact of zinc‐biofortified rice on zinc intakes of young Bangladeshi children
Authors: Arsenault Joanne E , Yakes Elizabeth A , Lewis Bess , Islam M Muniril , Hossain Bakhtiar , Ahmed Tahmeed , Hotz Christine , Brown Kenneth H 
Published: June 2021

BackgroundYoung children in Bangladesh are at risk of zinc deficiency due to a rice‐based diet with few animal‐source foods. Breeding rice for higher zinc content would offer a sustainable approach to increase zinc intakes.ObjectivesTo quantify usual rice and zinc intakes in young children and estimate the potential impact of zinc‐biofortified rice on zinc intakes.MethodsWe measured dietary intake in a representative sample of 480 children ages 24–48 mo in rural communities from two districts, Trishal (T) and Pirgaccha (P). Food intakes were estimated by weighed records in homes on 2 non‐consecutive days. Serum zinc concentrations were determined in a sub‐sample of children.ResultsMedian (25th, 75th pct) rice intakes of children were 144 (110, 179) g/d in T and 123 (88, 164) g/d in P; and median zinc intakes were 2.4 (2.0, 2.9) mg/d in T and 2.5 (2.1, 3.0) mg/d in P. 27% and 19% of children had inadequate zinc intakes (<2 mg/d) in T and P, respectively. 36% and 11% of children in T and P, respectively, had low serum zinc concentrations (<65 μg/dL) after adjusting for infection status. Rice was the highest source of zinc intakes, providing 59% and 41% of dietary zinc in T and P, respectively. If the rice zinc content were increased by 50% or 100%, the probability of inadequate zinc intakes would decrease to 8% or 3–4%, respectively.ConclusionsYoung children in rural Bangladesh have inadequate intakes of zinc, and zinc‐biofortification of rice has potential to markedly improve the zinc adequacy of the children's diets.Funding: HarvestPlus, Washington, DC
The Cortisol Response to a Buffet Meal Changes with Energy Restriction in Overweight Women
Authors: Witbracht Megan Gage , Thomas Anthony P. , Souza Elaine , Horn William F. , Adams Sean H. , Laugero Kevin , Van Loan Marta D. , Keim Nancy L. 
Published: June 2021

Research has suggested that stress affects eating behavior. We examined the relationship between cortisol and food choice at a buffet meal before and in response to a 12‐wk intervention (I) with an energy‐restricted diet. Overweight females (ages 20–45; n=49) maintained body weight (BW) during a 3‐wk baseline (B) period and lost weight during energy‐restriction (500 kcal/d deficit). The eating behavior protocol was conducted at B wk 0 and I wk 11 and included the provision of a standardized breakfast & lunch followed by ad lib buffet dinner. Salivary cortisol was measured at 10 specific times on both test days. Percent BW and fat loss averaged 5.9% and 3.0%, respectively. Energy (kcal), carbohydrate (CHO), fat and protein (PRO) intake at the buffet averaged 1345kcal, 134g, 63g, 64g, and ranged from 420 to 2667kcal, 43 to 297g, 11 to 126g, and 21 to 126g, respectively. Energy and grams of CHO, fat or PRO intake did not differ between test days. Analysis of the cortisol data revealed a correlation between kcal and cortisol taken 30 min after the completion of the buffet meal (r= 0.470; p=0.001) but only at wk 11. Similarly, cortisol was correlated with intakes of CHO (r=0.512; p=0.001), fat (r=0.375; p=0.008) and PRO (r=0.325; p=0.023). These data suggest factors related to energy restriction may increase the sensitivity of the hypothalamic‐pituitary‐adrenal axis to food intake.Funding: NDC/ARS Project 5306‐51530‐016‐00D
Maternal Green Tea Extract Supplementation Ameliorates Insulin Resistance in Male Offspring from Dams Fed a High‐Fat Diet
Authors: Li Shiying , Li Edmund Tsze Shing 
Published: June 2021

Green tea (GT) possesses beneficial effects against obesity and insulin resistance (IR). This study aimed to test the hypothesis that maternal green tea supplementation alleviates metabolic derangements in offspring born from obese dams. Female SD rats were fed a low‐fat (LF), high‐fat (HF), 0.75% or 1.0% GT extract added HF diet (HT1, HT2) from 8 wk before mating until end of lactation. GT dams tended to gain less during gestation but birth weight and litter size were not affected. There were 6 dam/pup diet groups: LF/HF, HF/HF, HF/HT1, HF/HT2, HT1/HF and HT2/HF. On d21 postpartum, GT dams had less visceral fat and lower insulin level than HF dams (n=8, p < 0.05). Body weight of pups from GT dams on d21 were lower (p < 0.05), but not on d91 than from HF dams. On d91, HT1/HF and HT2/HF rats had lower IR index than HF/HF and HF/HT1 rats (n=7–9, p < 0.02). Rats from GT dams had higher expression of uncoupling protein 1 in brown adipose tissue; adiponectin in adipocytes and peroxisome proliferator‐activated receptor‐γ coactivator‐1α in gastrocnemius but lower expression of hepatic glucose‐6‐phosphatase than HF/HF rats (p < 0.05). Hence, offspring of GT dams had better glucose handling and insulin sensitivity, and maternal exposure is more effective than postnatal GT supplementation. These results highlight the potential impact of dietary bioactive compounds on fetal development via metabolic programming. (Supported by a HKU grant)Grant Funding Source: The University of Hong Kong
Activated Farnesoid X Receptor inhibits growth of tamoxifen‐resistant breast cancer cells.
Authors: Giordano Cinzia , Vizza Donatella , Panza Salvatore , Barone Ines , Bonofiglio Daniela , Fuqua Suzanne A , Catalano Stefania , Andò Sebastiano 
Published: June 2021

BackgroundFarnesoid X Receptor (FXR) is mainly expressed in enterohepatic district where regulates lipids metabolism and glucose homeostasis. Recently, new functions of FXR were discovered including its capability to induces apoptosis in breast cancer cells, but the role of FXR in modulating growth of these cells are not fully elucidated.ResultsIn this study we evaluated the effects of chenodeoxycholic acid (CDCA), natural ligand of FXR, on growth of breast cancer cell lines sensitive (MCF‐7) and resistant to tamoxifen (MCF‐7TR). Using MTT assay we found that CDCA as well as GW4064, a specific synthetic FXR agonist, reduced cell viability in MCF‐7 and in a higher extent in MCF‐7TR cells. Furthermore, results from anchorage independent growth assay (soft agar) demonstrated that CDCA inhibited tamoxifen‐resistant colonies formation as well as Epidermal Growth Factor (EGF) induced growth in MCF‐7TR cells. Western blot analysis and real‐time RT‐PCR revealed that FXR activation determined a reduction of HER2 expression and consequently an inhibition of EGF‐mediated HER2 and p42/44 MAPK phosphorylation in MCF‐7 TR cells.ConclusionThese data suggest that FXR ligand‐dependent activity, blocking HER2/MAPK signaling, may reverse antiestrogen resistance in human breast cancer cells and could represent a new therapeutic tool to treat breast cancer patients that develop hormonal resistance.
A New Application for the Drug Tranilast: Effects on Breast Cancer Cell Proliferation, Migration, and Invasion
Authors: Jothy Serge , Ace Olga , Subramaniam Venkateswaran , Prud'homme Gerald 
Published: June 2021

BackgroundTranilast (Rizaben®) has been used to treat allergic and auto‐immune diseases for the last 26 years. The objective of this study was to investigate whether tranilast also has an effect on breast cancer cell biological features relevant to cancer progression, based on the its mechanism of action which involves TGFβsignaling.MethodsCultures of the BT‐474 human breast cancer cell line were used. Cell proliferation, clonogenicity, cell migration, endoglin and MMP‐9 expression were assessed by: MTT assay, soft agar colony formation, wound assay and immunocytochemistry respectively.ResultsTranilast was found to inhibit breast cancer cell proliferation by 70%. In addition, the drug decreased by 54% the number and size of cell colonies grown in soft agar, consistent with a decrease in clonogenicity. The closure of wounds made in cancer cell monolayers was slowed (55%) by Tranilast, consistent with an inhibitory effect on tumor cell migration. Endoglin, which plays a role in TGFβ signaling, was downregulated by the drug. MMP‐9, which is a metalloproteinase involved in tumor invasion and metastasis was also decreased by tranilast.ConclusionsThese results indicate that tranilast exerts inhibitory effects on key biological features of human breast cancer cells. The results are consistent with an anti‐tumor effect which can be exploited in preclinical and clinical therapeutic trials.
Extracellular matrix changes in melanoma promote tumor cell migration
Authors: Grahovac Jelena , Wu Qian , Conrads Thomas P , Wells Alan 
Published: June 2021

In melanoma, invasion through the extracellular matrix (ECM) is a harbinger of dissemination and mortality. We find that changes in ECM composition of invasive human melanoma specimens resemble changes found during skin wound healing. Most highly upregulated in invasive melanoma was Tenascin C (TN‐C). Simultaneously, the matrix proteoglycans decorin and lumican were downregulated and the level of collagen I was decreased as the dermal matrix became ‘less mature’. The cellular origin of these matrix changes are not fully settled; still the melanoma cell lines, derived from tumors of different stages, express varied increased levels of TN‐C and fibronectin and decreased levels of collagen I compared to normal human melanocytes. Cells expressing higher amounts of TN‐C migrate faster in wound healing assays; on TN‐C pre‐coated surfaces both melanoma cells and normal melanocytes increase migration. Our group previously showed that the EGF‐like repeats of TN‐C are able to bind the EGFR with μM affinity and preferentially activate the motogenic signaling cascades. This upregulation of EGFR‐activating TN‐C is concomitant with downregulation of decorin and lumican, which have been reported to dampen EGFR signaling. Therefore, we hypothesize that the increased levels of TN‐C in melanomas promote tumor cell migration and invasion heralding dissemination through enhanced EGFR signaling.Funding: Internal (AW).
Removal of Integrin Linked Kinase from Hepatocyte Leads to a Prolonged Proliferative Repose to a Mitogenic Stimuli
Authors: Donthamsetty Shashikiran , Michalopoulos George 
Published: June 2021

We have recently demonstrated that disruption of ECM/Integrin signaling via elimination of Integrin linked kinase (ILK) interferes with signals leading to termination of regeneration. This study investigates the role of ILK in hepatocyte proliferation induced by Phenobarbital (PB). PB was administered in drinking water for 10 days. Steady supply of PB led to a modest nuclear translocation of CAR in WT and ILK−/ − mice. CAR target like CYP2B6 was also increased in both the groups. We then looked at the hyperplastic response of PB in both the groups. 10 days of phenobarbital administration led to a 3 times increased liver to body weight ratio as compared to 0 day in the ILK−/ − mice while the WT mice show only a 2 times increase. ILK−/ − mice also have increased percent of PCNA positive cells and mitotic cells even at day 5 and 10 of phenobarbital administration suggestion a prolonged proliferative response. Signaling pathways altered in ILK−/ − mice included enhanced HGF‐cMet signaling, increased downstream activation of mitogenic molecules like cyclin D1, increased activation of YAP pathways and downregulation mitoinhibitory molecules like TGF‐β1. In summarize, ECM proteins communicate with the signaling machinery of dividing cells via ILK to regulate hepatocyte proliferation and termination of the proliferative response. Lack of ILK in the hepatocytes have prolonged proliferative response to a mitogenic stimuli suggesting defect in termination of proliferative response.The work is supported by a R01 grant (5R01CA035373‐26) titled “HGF in Liver Development, Regeneration and Neoplasia”
Transcription Elongation links to Histone Methylation
Authors: Jones Katherine A , Bres Vanessa , Zhang Lirong 
Published: June 2021

Many steps in gene expression and mRNA biosynthesis are coupled to transcription elongation. The P‐TEF‐b complex (CycT1:CDK9) overcomes a block to transcription elongation established by the negative‐acting elongation factors, DSIF and NELF. In addition, P‐TEFb phosphorylates the RNAPII CTD, which loads complexes involved in cotranscriptional mRNA processing, surveillance, export, and histone H3K36 methylation. We recently showed that P‐TEFb associates with an alternative splicing factor, SKIP/SNW1, which is required for HIV‐1 Tat transactivation, and will discuss how SKIP stimulates transcription elongation and histone H3K4 methylation at the viral promoter. Thus communication between transcription and splicing occurs in both directions, as the SKIP splicing protein plays a direct role in transcription elongation and H3K4 methylation.We recently reported that Spt6, a transcription elongation factor and histone H3 chaperone, binds directly to the P‐TEFb‐phosphorylated RNAPII CTD to recruit factors to the elongation complex. This megacomplex includes the Hypb/Setd2 histone methyltransferase, which is a CTD‐interacting enzyme that directs H3K36me3 to the coding region of active genes. The assembly of this complex depends upon P‐TEFb activity and is strongly up‐regulated in activated T cells.
Signaling Pathways that Regulate Skeletal Muscle Atrophy and Hypertrophy
Authors: Glass David J. 
Published: June 2021

Skeletal muscle atrophy is a significant co‐morbidity seen in a variety of diseases, including Congestive Heart Failure, renal failure, cancer, and AIDS. Even during simple muscle inactivity, such as when a cast is put on a limb, the affected muscle can decrease by as much as 50% in mass, with a coincident decrease in strength. Two E3 ubiquitin ligases – MuRF1 (Muscle RING Finger 1) and MAFbx (Muscle Atrophy Fbox protein, which is also known as Atrogin), are transcriptionally upregulated in all physiological settings of muscle atrophy that have been analyzed. The pathways which regulate these ligases will be discussed. Also, more recently, potential substrates of MuRF1‐ which comprise part of the skeletal muscle contractile apparatus ‐ have been elucidated. These substrates, including components of the sarcomeric thick filament, will be discussed, as well as conditions that can modulate MuRF1's activity.An additional important modulator of muscle mass is myostatin, a TGF‐beta family member. We have recently conducted studies demonstrating the ways that myostatin perturbs muscle mass and function, which both confirms other studies showing an inhibitory effect on muscle differentiation, but which also shows several important points of cross‐talk between myostatin signaling and Akt/TORC1 signaling.
IQGAP1 is a Novel HER2 Binding Partner and Regulates HER2‐Mediated Cell Proliferation
Authors: White Colin David , Li Zhigang , Niepel Mario , Sacks David Barry 
Published: June 2021

The receptor tyrosine kinase HER2 is overexpressed in 25–30% of breast carcinomas. These tumors often have an increased rate of proliferation and give rise to more frequent metastases than HER2(−) neoplasms. HER2(+) breast cancer is treated with Trastuzumab, but ~60% of patients do not respond. Of those who do, ~15% subsequently develop metastatic disease. An understanding of the molecular mechanisms of HER2 signaling is necessary to develop novel therapeutics. IQGAP1 is a ubiquitously expressed 190 kDa scaffold protein. Through interaction with multiple binding partners, IQGAP1 regulates processes such as cell proliferation and migration, cell‐cell adhesion and cytoskeletal remodeling. IQGAP1 plays defined roles in several human malignancies, including those of the breast. Here, we investigate the interaction between IQGAP1 and HER2. In vitro assays using purified IQGAP1 and the GST‐tagged intracellular domain of HER2 (GST‐HER2) revealed that IQGAP1 binds HER2. GST‐HER2 binds IQGAP1 in Sk‐BR‐3 cells, and endogenous HER2 co‐immunoprecipitates with endogenous IQGAP1 from cell lysates. Analogous to other IQGAP1 binding partners, calmodulin abrogates the association of IQGAP1 with HER2. Overexpression of IQGAP1 significantly increases Sk‐BR‐3 cell proliferation, while siRNA‐mediated knockdown of IQGAP1 significantly reduces proliferation. These data suggest that IQGAP1 may be a potential target for HER2(+) breast cancer therapy.Work in the authors' laboratory is funded by the NIH (to D.B.S.) and the DoD BCRP (to C.D.W).
Optional splicing of T‐Cell Intercellular antigen‐1 (TIA‐1), a RNA‐binding Protein Regulates VEGF Expression in Colorectal Cancer
Authors: Hamdollah‐Zadeh Maryam , Hoareau‐Aveilla Coralie , Varey Alexander H , Amin Ellianna Mohamed , Ladomery Michael R , Harper Steve J , Bates Dave O 
Published: June 2021

To determine the role of post‐transcriptional regulation of Vascular Endothelial Growth Factor (VEGF) in colorectal cancer we investigated the relationship between VEGF and the RNA binding protein TIA‐1. An endogenous splice variant of TIA‐1 was expressed in 66% of colon cancer samples and in cancer cells with high angiogenic VEGFxxx expression. This splice variant resulted in a truncated protein termed short TIA‐1 (sTIA‐1). Whereas full length TIA‐1 bound to the VEGFxxx isoform (RNA immunoprecipitation, MS2‐Maltose Binding Protein assay) there was no TIA‐1 binding in cells expressing sTIA‐1. siRNA knockdown of TIA‐1 resulted in higher expression of total VEGF. Using VEGF terminal exon luciferase reporter constructs, TIA‐1 reduced translation of the angiogenic (exon 8a) but not the anti‐angiogenic (exon 8b) isoforms.In summary, we show that over expression of the wild type TIA‐1 in adenocarcinoma cells expressing sTIA‐1 results in restoration of the anti‐angiogenic VEGF isoforms. This suggest that TIA‐1 can act as both a splicing and splice specific translational regulator of VEGF and alternative splicing of TIA‐1 could lead to enhanced angiogenesis in colorectal cancer. Supported by AICR.
An Unusual Branching Pattern of the Axillary Artery
Authors: Singh Keerti , Rao Ramachandra 
Published: June 2021

During routine dissection of a female cadaver, an unusual branching pattern of right axillary artery was observed. It was seen that second part of axillary artery gave only one branch i.e. the thoracoacromial artery. While its third part gave two branches namely, the anterior circumflex humeral and subscapular. The subscapular artery (with its usual branches) also gave origin to the lateral thoracic and the posterior circumflex humeral branch. It furthur continued as brachial artery from which arose anterior and posterior descending (radial collateral) arteries (branches of profunda), which coursed through the lower triangular space along with the radial nerve.Grant Funding Source: University