bluuebunny/crossref_metadata_2025_split huggingface dataset:
Qatari and Indian Asians Type 2 Diabetes in the State of Qatar; IntraCellular Cations and Ultra Structural Study of Platelets
Authors: Afifi Nahla Maher , Ewis Soliman M. , Benslimane Fatiha M. , Bejaoui Yosra Ridha 
Published: June 2021

Diabetes mellitus is one of the main causes of cardiovascular diseases in Qatar and platelets play a key role in these events.The aims of this project is to study ultrastructural changes in diabetic platelets, intraplatelets concentration of Ca and Mg and their relation to insulin, and to investigate if there are any racial differences associated with platelets abnormalities. Diabetic groups included 34 Qatari (Q) and 32 Asian Indian (AI). Control groups included 21 (Q) and 13 (AI). The results indicated that intraplatelet Ca was significantly higher in both diabetic (Q & AI) groups compared to corresponding controls (Q; 0.134 ± 0.0728 vs. 0.097 ± 0.034, p< 0.05) and (AI; 0.179 ± 0.0738 vs. 0.117 ± 0.0854, p< 0.01). Comparing to control; a significant decrease in Mg level for the Qatari diabetics (7.4 ± 4.4 vs. 14.4 ± 6.1, p< 0.05) associated with a significant decrease in the insulin level for the same group (26.1 ± 18.2 vs. 21.8 ± 19.6, p< 0.05). The MPV showed significant increase in diabetic groups compared to the controls with (Q; 8.4 ± 1.1 vs. 7.8 ± 0.6, p< 0.05) and (AI; 8.8 ± 0.6 vs. 7.7 ± 0.3, p< 0.05), and a significant increase in (AI) diabetics compared to (Q) diabetics p< 0.05. Abnormal structural characteristics were seen under TEM in both diabetic groups Q & AI with clear evidence of microthrombus in the AI group. This may explain the higher incidence of CV events among the Asian Indians diabetics compared to the other ethnic groups.This project was funded by QU&UREP.
Electron microscopy reveals that archaeal box C/D sRNPs are di‐sRNPs
Authors: Bleichert Franziska , Gagnon Keith T , Brown Bernard A , Maxwell Stuart , Unger Vinzenz M , Baserga Susan J 
Published: June 2021

Methylation of ribosomal RNA (rRNA) is required for optimal protein synthesis. Multiple 2′‐O‐ribose methylations are carried out by small (nucleolar) box C/D guide ribonucleoproteins (s(no)RNPs), which are ubiquitous in nature from archaea to eukaryotes. Each site of methylation is dictated by base pairing between the specific guide s(no)RNA component of the s(no)RNP and the target rRNA. We have determined the first structure of a reconstituted and catalytically active box C/D sRNP by electron microscopy and single particle analysis. Our results reveal that archaeal box C/D sRNPs form an unexpected di‐sRNP structure which is required for efficient methylation activity, challenging the conventional paradigm of box C/D s(no)RNP architecture.This work was supported by the NIH and the Boehringer Ingelheim Fonds.
Alternative polyadenylation of poly(A) binding protein nuclear 1 (PABPN1) mRNA
Authors: Hague‐Canto Lisa K. , Tian Bin , Lutz Carol S. 
Published: June 2021

Polyadenylation is a 3' end RNA processing event that contributes to the regulation of gene expression by affecting turnover, stability, export, and translation of mRNA. Approximately 53 % of all human genes have multiple polyadenylation sites (PAS). Regulation at the level of alternative polyadenylation has begun to be investigated, but still requires much more elucidation.Bioinformatics has identified unique alternative polyadenylation of a polyadenylation factor mRNA, poly (A) binding protein nuclear 1 (PABPN1). The mRNAs of this polyadenylation factor contains multiple polyadenylation sites.Two polyadenylation signals were found for the PABPN1 mRNA. The proximal PAS is predicted from bioinformatics to be the strong polyadenylation site. The distal PAS was suggested to be a weaker site. However, we found the distal PAS contains putative novel auxiliary upstream polyadenylation elements. There are two G‐rich elements found in the upstream region of PABPN1 mRNA that are very highly conserved, suggestive of important function. Mutations of these two G‐rich elements seem to exhibit opposing effects on polyadenylation.Previous studies from other labs have shown that G‐rich elements located downstream of polyadenylation sites enhance cleavage, and affect polyadenylation signal usage, but remains unexplored when upstream. Research supported by NIH and the Foundation of UMDNJ grants.
Purification and Characterization of the Cytosolic TRiC Complex from HeLa Cells
Authors: Knee Kelly Marie , Goulet Daniel Robert , Jameel Shea , King Jonathan A 
Published: June 2021

The group II chaperonin TRiC is required for actin and tubulin folding and is thus essential for the reproduction of all eukaryotic cells. We have purified Human TRiC from cervical adenocarcinoma (HeLa) cells. To assess the substrate‐binding properties of Human TriC, we are characterizing its interactions with human γCrystallins. The γCrystallins are a family of β‐sheet eye lens proteins, whose partially folded intermediates have been well‐characterized. The Archaeal group II chaperonin Mm‐Cpn, from M. marapaludis, is a homolog of human TriC, and it has been shown that the complex suppresses aggregation of partially folded Human γCrystallins, and refolds the Crystallins to a native‐like conformation. We are investigating the potential of Human TRiC to suppress aggregation and restore unfolded γCrystallin to a native fold in a similar manner to Mm‐Cpn, using UV/Vis spectroscopy, and size exclusion chromatography. In collaboration with Wah Chiu (Baylor College of Medicine) and Judith Frydman (Stanford University) of the Center for Protein Folding Machinery, we are attempting to visualize the crystallin substrate in the chaperonin/substrate complex by Cryo‐EM.Supported by an NIH Roadmap Award.
Secondary purification and oligomeric structure of three class II small heat shock proteins from Zea maize
Authors: Nau Christopher T. , Tims Hannah S. , Bouchard Robert A. , Meulia Tea , Pett Virginia B. 
Published: June 2021

Small heat shock proteins (sHsps) are chaperones that bind to a substrate in order to reduce undesirable aggregation, holding substrate in a folding intermediate prior to the restoration of the substrate's native conformation by other ATP‐activated chaperones. To this end, sHsps are often expressed in vivo in response to increased temperature or other stress. The goal of the research was to identify a successful secondary purification protocol for three class II small heat shock proteins from Zea maize: 17.0, 17.6, 17.8 (designated according to their size in kilodaltons) and to analyze the oligomeric structure through a combination of native PAGE, glutaraldehyde cross‐linking, transmission electron microscopy (TEM), and fluorescence resonance energy transfer. Anion exchange chromatography under denaturing conditions was found to be effective in purifying the sHsps. TEM revealed two oligomeric sizes of ~12 and ~25 nm, larger than what has been found for other class II sHsps, while chemical cross‐linking suggests that the oligomeric structure of the sHsp is a dodecamer.This work was supported in part by a grant to The College of Wooster from the Howard Hughes Medical Institute through the Undergraduate Science Education Program.
Characterization and C‐terminally truncational analysis of a 70‐kD molecular chaperone, DnaK, from the industrial bacterium Bacillus licheniformis
Authors: Chi Meng‐Chun , Liang Wan‐Chi , Lin Long‐Liu , Huang Hsien‐Bin 
Published: June 2021

AimsThe aim of this study was to characterize the recombinant Bacillus licheniformis DnaK (BlDnaK) and to enhance the understandings of allosteric regulation in this protein by deletion mutations.Methods and ResultsThe heat shock protein 70, heat shock protein 40 (DnaJ), and nucleotide exchange factor (GrpE) genes of B. licheniformis were overexpressed in Escherichia coli. The purified BlDnaK had a Vmax of 32.5 nmol Pi/min and a KM of 439 μM. In vivo, the dnaK gene allowed an E. coli dnaK756‐ts mutant to grow at 44oC. Simultaneous addition of DnaJ and GrpE synergistically stimulates the ATPase activity of BlDnaK by 11.7‐fold. A T76W mutant and three C‐terminally truncated BlDnaKs were also constructed to evaluate the role of up to C‐terminal 255 amino acids in allosteric regulation. The specific ATPase activity for BlDnaK, T76W, T76W/δC120, T76W/δC249, and T76W/δC255 was 1.45, 1.06, 2.32, 6.43, and 1.81 nmol/Pi/min/mg, respectively. Measurement of intrinsic tryptophan fluorescence revealed the significant alterations of the microenvironment of aromatic amino acids in the C‐terminally truncated BlDnaKs. The temperature‐dependent signal in the far‐UV region for T76W was consistent with that of BlDnaK, but the C‐terminally truncated mutants showed a higher sensitivity towards temperature‐induced denaturation.ConclusionsThis study provides evidence that BlDnaK has biochemical and molecular chaperone properties of the Hsp70/DnaK family. Our preliminary results also showed that the ATPase activity of the variants was stimulated differently from wild‐type BlDnaK in presence of BlGrpE.
Ca2+ regulation of the Na+/Ca2+ exchanger
Authors: chaptal vincent , mercado‐besserer Gabriel , ottolia michela , nicoll deborah , philipson kenneth , abramson jeff 
Published: June 2021

Ca2+ is an essential ion involved in a multitude of processes essential for life. In the heart, Ca2+ influx into the cytosol leads to muscle contraction. In order for the heart to function properly, the same amount of Ca2+ entering the cytosol must be removed, to allow the heart to relax and refill with blood. Defects in Ca2+ cycling result in smaller and slower calcium transients that are characteristic of heart failure. The Na+/Ca2+ exchanger (NCX1.1) serves as the major mechanism for Ca2+ extrusion from the myocyte, utilizing the Na+ electrochemical gradient to counter‐transport three Na+ into the cell while extruding one Ca2+. In addition, NCX1.1 is also regulated by these two ions, although these mechanisms remain incompletely understood.Structurally, NCX1.1 has nine predicted trans membrane helices and a large cytoplasmic loop of approximately 500 residues. This loop contains two Ca2+ Binding Domains (CBD1 & CBD2) that regulate NCX1.1 activity. We solved the structures of CBD1 and CBD2 using X‐ray crystallography and performed a comprehensive mutational and electrophysiological analysis that shed new light on their crucial role in the regulation of NCX1.1 activity.To learn how regulation occurs, we will explore the interactions of these regulatory Ca2+ binding domains with each other, as well as with other parts of NCX1.1.This work has been funded by AHA and HFSP.
HDAC inhibitor, TSA, downregulates Myc transcription in human cervical cancer cell lines
Authors: Li Hui , Li Xiaoling , Liu Xuefeng , Wu Xinxing 
Published: June 2021

Histone deacetylase (HDAC) inhibitors have shown promise in clinical cancer therapy and to induce p21 expression in a p53‐independent manner via increased acetylation of the chromatin at the Sp1 sites in the p21 promoter region. Our previous study has shown that Trichostatin A (TSA), a HDAC inhibitor, induces p21 through downregulation of Myc expression and release of Myc bound from the p21 promoter in HeLa cells. However, the mechanism of how TSA downregulates Myc remains unclear. In this study, we treated two human cervical cancer cell lines, HeLa and SiHa, with TSA, confirming that TSA decreased Myc protein with Western blot. The decreased level of Myc might be due to a decreased stability of Myc protein or downregulated transcription of Myc in TSA treated cells. Our results from both regular RT‐PCR and real time RT‐PCR demonstrated a significant decrease of Myc mRNA in TSA treated cells compared to that in untreated cells. Thus, TSA treatment downregulates Myc expression at the transcriptional level in human cervical cancer cell lines. The results provide the possibility that TSA may alter chromatins at the Myc promoter via direct or indirect modifications. Chromatin changes at the Myc promoter in TSA treated cells are being investigated.This work was supported by grant from the National Natural Science Foundation of China (No. 30500465, No. 30810103052) .
Regulator of G protein Signaling 6 (RGS6) is Upregulated in Cancer cells by Doxorubicin and Modulates Doxorubicin‐induced DNA damage signaling
Authors: Huang Jie , Chatterjee Tapan K , Mayuzumi Daisuke , Fisher Rory A 
Published: June 2021

RGS proteins were discovered as negative regulators of heterotrimeric G protein signaling. The precise biological role of all but a few RGS proteins is unknown, as is the need for such a large structurally diverse protein family if RGS proteins function only as G protein GAPs. Here, we provide new evidence suggesting a role of RGS6 in regulating DNA damage responses in cancer cells. Doxorubicin (Dox) treatment of cancer cell lines led to dramatic increases in RGS6 protein levels, which were undetectable in unstimulated cells. Dox induction of RGS6 protein was accompanied by significant increase in RGS6 gene transcription as assessed using an RGS6 gene promoter reporter. Further, expression of RGS6 in MCF7 cells promoted phosphorylation of p53 in response to a low dose of Dox, which alone had no effects. This activity of RGS6 requires its DEP domain but is independent of its interaction with G proteins. RGS6 expression in several cancer cell lines promoted cell cycle arrest and growth suppression. ATM, an upstream activator of p53, may be involved in RGS6‐induced p53 phosphorylation, as expression of RGS6 promotes ATM activation in response to a submaximal dose of Dox. Our data identify RGS6 as a target of Dox and suggest that RGS6 may play a novel role as a modulator of chemosensitivity in cancer cells. Importantly, these actions of RGS6 are independent of its interaction with G proteins.NIH (GM075033) and AHA (0750057Z).
ANTIBACTERIAL PROPERTIES OF SOME NEW PYRIDO – 1,2,4 – TRIAZOLE‐ 3 – THIONES
Authors: Govori Sevdije R , Rifati Arleta , Leci Osman , Haziri Arben 
Published: June 2021

Abstract8‐amino‐[1,2,4] triazolo [4,3‐a] pyridine‐ 3(2H) ‐ thione (7), 6‐amino‐[1,2,4] triazolo [4,3‐a] pyridine ‐ 3(2H) ‐ thione (8) and 5‐amino‐1,2‐dihydro‐3H‐pyrazolo [4,3‐b] pyridine ‐ 3 ‐ thione (9) ,are synthesized through corresponding hydrazine derivatives (4 ‐6) with CS2 in very good yields.The identity and structure of these compounds was proven on the basis of spectral data and elemental microanalysis.The new compounds (7‐9) showed strong activity in reducing the microbial growth. The inhibitory effects of compounds were affected by their structure. All compounds showed the most effective antibacterial activity against Escherichia coli , Staphylococcus aureus , and Klebsiella pneumonie .
Flavonoids can be cytotoxic to breast tumor cells despite inhibiting caspase‐3
Authors: Beckford Jeremy , Yadegarynia Sina , White J Brandon , d'Alarcao Marc 
Published: June 2021

Flavonoids are polyphenolic plant natural products found extensively in the human diet. This class of compounds has been of considerable medicinal interest because of numerous reports of anti‐inflammatory and anti‐cancer activities. However, a detailed understanding of the biochemical mechanism of these activities is lacking because the compounds have been reported to be antioxidants and also affect multiple cell signaling pathways, including those mediated by protein kinase C, phosphoinositide 3‐kinase, Akt/protein kinase B, tyrosine kinases, and mitogen activated protein kinase.We have undertaken a study to determine which of the various cellular activities are necessary and sufficient to induce cell death in a variety of breast cancer cell lines. As part of this study, we have evaluated the ability of various flavonoids to induce apoptosis by evaluating their effect on various markers, including caspase 3/7 activation, and cytochrome C release from the mitochondria. We have found that several flavonoids, in addition to inducing cell death are inhibitors of caspase 3. This poster will report the details of our studies on the inhibition of caspases by flavonoids.Support of research was through the National Institutes of Health RISE Program at San Jose State University to JB.
Luteolin attenuated pro‐inflammatory conditions induced by activated microglia and protected against neuronal cell death
Authors: Jang Saebyeol , Johnson Rodney W 
Published: June 2021

Excessive production of proinflammatory mediators by activated brain microglia plays an important role in sickness behavior and neurodegenerative disorders. Luteolin, a flavonoid found in high concentrations in celery, green pepper, and perilla leaf and seeds, has been shown to reduce proinflammatory molecules produced by lipopolysaccharide (LPS)‐stimulated macrophages and microglia. In the present study, the anti‐inflammatory and subsequent neuroprotective effects of luteolin were investigated. Pretreatment of primary microglia and BV2 murine microglial cells with luteolin inhibited LPS‐stimulated production of proinflammatory cytokines such as TNF‐α and IL‐1β at both the gene and protein levels. Luteolin also suppressed LPS‐induced nitric oxide release in BV2 cells by regulating the expression of inducible nitric oxide synthase. In addition, the release of prostaglandin E2 and cyclooxygenase‐2 mRNA expression were inhibited by luteolin. In addition, treating Neuro‐2a cells with conditioned media from LPS‐stimulated microglia resulted in neuronal cell death. However, treating microglia with luteolin prior to LPS reduced neuronal cell death in a dose‐dependent manner. These results suggest that luteolin may be a useful agent counteracting neurotoxicity associated with activated microglia. This work was supported by NIH grants AG16710 and MH069148.Grant Funding SourceNIH
Role of grape powder extract (GPE), quercetin (QUE), and resveratrol (RSV) in attenuating markers of inflammation in primary cultures of human (pre)adipocytes
Authors: Chuang Chia‐Chi , Bumrungpert A. , Kennedy A. , Martinez K. , Walker‐West T. , McIntosh M. 
Published: June 2021

Obesity‐associated inflammation in white adipose tissue (WAT) is strongly implicated in the development of insulin resistance. GPE is rich in phenolic phytochemicals like QUE and RSV that possess anti‐inflammatory properties. Thus, we examined the ability of GPE, QUE, and RSV to attenuate tumor necrosis factor (TNF)‐α ‐mediated activation of mitogen‐activated protein kinases (MAPK), nuclear factor kappa B (NFκB) and activator protein (AP)‐1 and induction of inflammatory genes in primary cultures of human (pre)adipocytes. We found that GPE, QUE, and RSV attenuated TNF‐α ‐induced expression of inflammatory adipocytokines [i.e., interleukin (IL)‐6, IL‐1β, IL‐8], markers of macrophage recruitment into WAT [i.e., monocyte chemoattractant protein (MCP)‐1], and negative regulators of insulin sensitivity [i.e., protein tyrosine phosphatase (PTP)‐1B]. Furthermore, we found that GPE and QUE attenuated TNF‐α ‐activated MAPK (i.e., ERK1/2, JNK1/2), NFκB, and AP‐1 (i.e., c‐Jun). RSV, however, only modestly attenuated TNFα‐activation of NFκB and c‐Jun, and had no effect on TNF‐α ‐activation of ERK1/2 and JNK1/2. Taken together, these data suggest that GPE, QUE, and RSV attenuate TNF‐α ‐mediated inflammation in primary cultures of human (pre)adipocytes by different upstream mechanisms. (Funded by the WB Kellogg Institute for Food and Nutrition Research; Grape Powder supplied by the CA Table Grape Com.)Grant Funding SourceWB Kellogg Institute for Food and Nutrition Research
Improved weight and body composition following a structured diet plan incorporating healthy convenient prepared meals
Authors: Summers Amber , Nguyen Von , Brosnahan Jen , Zukley Linda , Lowndes Joshua , Pohl Rob , Reimers Kristin , Angelopoulos Theodore J , Rippe James M 
Published: June 2021

Excess body fat is a risk factor for the development of many chronic diseases. Lifestyle measures such as decreased caloric intake and increased physical activity constitute first line treatments to reduce excess body fat.We examined the effects of a DASH‐Style (DS; n=70) diet and exercise or exercise only (EO, n=58) program on cardiovascular risk factors in 128 participants (BMI 22‐40) for 24 weeks. Both groups received an exercise prescription recommending a minimum of 15 minutes of moderate physical activity, 3 days per week and progressing to 45 minutes, 4 days per week by week 12. They also met with an exercise physiologist once weekly for 12 weeks and biweekly thereafter. The DS group followed a reduced calorie eating pattern and incorporated one commercially prepared healthy frozen meal and one other selected grocery item each day for 24 weeks and received dietary counseling from a dietician once weekly for 12 weeks and biweekly thereafter. .After 24 weeks, the DS group reduced body weight (‐18.12 ± 10.66 vs ‐6.33 ± 8.24 lbs, p<0.001), BMI (‐2.90 ± 1.64 vs ‐1.00 ± 1.30 kg/m2, p<0.001), waist circumference (‐7.03 ± 4.53 vs ‐3.08 ± 3.79 cm, p<0.001), body fat percentage (‐5.93 ± 3.93 vs ‐1.64 ± 2.88%, p<0.001) and fat mass (‐18.59 ± 11.31 vs ‐6.01 ± 9.01 lbs, p<0.001) to a greater extent than the EO group.These data suggest that a structured diet plan that combines healthy prepared meals with regular walking exercise can successfully reduce weight and improve measures of adiposity. The convenience of ready to eat meals may improve compliance to a structured program of risk factor reduction
Dietary Fat Intake, Liver Function and Disease Progression in HIV+ Adults in Botswana, Africa
Authors: Baum Marianna K , Le Katherine , Moyo Sikhulile , Makhema Joe , Burns Patricia J , Sales Sabrina , Tsalaile Lesedi , Bussmann Hermann , Li Yinghui , Campa Adriana , Marlink Richard 
Published: June 2021

ObjectiveAlthough increased energy intake is associated with benefits in HIV+ patients, the effect of fat intake on HIV progression and liver function needs to be established.MethodsAfter consenting 714 HIV+ asymptomatic adults, blood was drawn for chemistries, CD4 cell count and viral load. 24‐Hour Recalls were collected and analyzed by Nutribase 7.0.ResultsMedium CD4 cell count was 424 cells/µL, mean age was 33±8.1 (78.8% < 40 years), and 72.5% were female. Mean dietary fat intake was 38.25±31.2 g; 36% of participants had BMI>25 kg/m2. Total fat intake was positively associated with alkaline phosphatase (β=0.002, p=0.0025) and gamma‐glutamyl transferase levels (β=0.111, p=0.005). Total fat intake (%) was significantly associated with total cholesterol (β=0.007, p=0.027) and LDL levels (β=0.006, p=0.04). Those in the first CD4 quartile (≤399 cells/µL) had higher mean LDL (2.5±0.8 vs. 2.3±0.8 mmol/L, p=0.0273) than the rest. Compared to those in the CD4 third quartile (≥550 cells/µL), those in the first and second quartile had higher alkaline phosphatase (76.44±21.3 vs. 68.2±20.9 U/liter, p=0.015). These relationships remained significant after adjusting for BMI.ConclusionThese findings support a significant association between increased dietary fat intake, adverse lipid profile, increased liver enzymes and HIV progression that is not affected by body composition.Funded by NIDA