bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational Prediction and Experimental Validation of the Lipid‐Binding Regions of Hsp70 Proteins
Authors: McCallister Chelsea , Donnelly Gabrielle , Le Dat , Nikolaidis Nikolas 
Published: June 2021

Hsp70s function in protein folding and refolding, transportation across biological membranes, and are necessary for cellular homeostasis under both physiological and pathological conditions. Apart from their intracellular functions, Hsp70s have also been found in close proximity or bound to biological membranes and in the extracellular milieu. It has been hypothesized that interaction of Hsp70s with specific lipids allows them to translocate and anchor to membranes, and subsequently be secreted. However, these hypotheses have not been directly tested, since the lipid‐binding regions (LBRs) of Hsp70s and the amino acids that mediate these interactions remain uncharacterized. To identify the LBRs of the Hsp70s, we have developed a new algorithm, because the existing protein‐domain‐identification algorithms fail to predict any known lipid‐binding domains in them. Application of our algorithm on HspA1A predicted two regions as putative LBRs. We tested these predictions experimentally and determined that both regions bind to lipids with high affinity. Therefore the experimental results support the predictions of our computational strategy and define two regions that mediate lipid‐binding on the HspA1A. We plan to expand the use of our algorithm to test the evolutionary conservation or divergence of the lipid‐binding function of Hsp70s using Hsp70s from evolutionarily key species.This project was supported by funds from CSUPERB and CSUF to NN
Expression of TLR9 in mouse and human lung and its role in lung inflammation in chicken barn air exposure
Authors: Schneberger David , Aulakh Gurpreet , Channabasappa Shankaramurthy , Caldwell Sarah , Singh Baljit 
Published: June 2021

Workers exposed to intensive animal housing facility air show signs of occupationally‐related lung dysfunction. These respiratory symptoms are associated with endotoxin, but within these environments gram negative bacteria may constitute only a small portion of the microorganisms present. In contrast, unmethylated DNA can be found in all bacteria, some viruses, and mould. Immune responses to this unmethylated DNA are mediated through the TLR9 receptor. Therefore, we sought to test expression of TLR9 in mouse as well as human lungs, to see if mice would be an appropriate model for an exposure study. We hypothesized that the immune response seen in the lungs of mice exposed to barn air would be altered in a TLR9‐deficient animal towards a less inflammatory state.We used immunohistology, immuno‐electron microscopy and in situ hybridization to show expression of TLR9 on bronchial epithelium, alveolar septal cells, and alveolar macrophage of mouse and human lungs. Having established similar receptor expression, a barn exposure study was done using a TLR9‐deficient mouse model. Mice were exposed to chicken barn air for 8 hours/day for 1, 5, or 20 days. Examination of bronchiolar lavage and serum against a panel of cytokines (IL‐1β, IL‐6, IL‐10, IL‐12, TNF‐α, and IFN‐γ) showed no significant differences after one day exposure. TNF‐α (p=0.06) levels in TLR9‐deficient mice were reduced in blood and lavage fluids after 5 days, and somewhat reduced at 20 days of exposure (p=0.14), while IFN‐γ was also reduced at 5 days(p=0.06) and remained reduced after 20 days (p=0.05). A reduction in lung neutrophils at 20 days was also seen. Our data shows similar expression patterns of TLR9 in mouse and human lungs, and that barn dust DNA may contribute to inflammation induced following exposure to chicken barn air.Grant Funding Source: NSERC
Effect of Jobelyn® (Sorghum Bicolor) on nitric oxide and arginase activity in sickle cell anaemic subjects (HbSS)
Authors: ANI ANTHONY AMAECHI , Imaga Ngozi Awa 
Published: June 2021

The objective of this in vivo study was designed to investigate the effect of jobelyn on nitric oxide synthase (NOS) and arginase activity in sickle cell anaemic subjects and to elucidate the biochemical pathways through which jobelyn aids in management of sickle cell anaemia; with arginase (EC 3.5.3.1) and nitric oxide synthase (EC 1.14.13.39) pathways under investigation. Both pathways are implicated in vaso‐occlusive crisis usually presented during sickle cell crisis. Three adult human subjects (n=3; Age: 24±3) that had not taken jobelyn prior to the study were recruited from the sickle cell clinic, lagos university teaching hospital. Blood samples were collected before administration, during administration and withdrawal (Day 0, Day7 & 14, and Day 28 respectively) for haematological, biochemistry, nitric oxide and arginase activity analysis. The mean haemoglobin concentration (Hb) g/L on Day 7 and Day 14 were statistically higher than Day 0(P<0.05), while Day 28 is lower than Day 7 and Day 14 (P<0.05). There was no significant difference in nitric oxide concentration μM and arginase activity U/L in all sampling days (P>0.05). In conclusion, administration of jobelyn increases the Hb concentration in sickle cell anaemic subjects, but does not affect nitric oxide concentration and arginase activity.No support was received.
Targeted disruption of Pde3b, but not Pde3a, protects murine heart from ischemia/reperfusion injury: Proteomic approaches to possible mechanisms
Authors: Chung Youn Wook , Chen Yong , Gucek Marjan , Murphy Elizabeth , Manganiello Vincent 
Published: June 2021

The Pde3 gene family contains two subfamilies, PDE3A and PDE3B, which are generated from distinct, but closely related, genes. Cilostazol, a PDE3 inhibitor, has been reported to protect rabbit and murine heart against ischemia/reperfusion (I/R) injury. Targeted disruption of Pde3b, but not Pde3a, protected the heart from I/R injury, with significantly improved postischemic recovery of left ventricular developed pressure and reduced infarct size.Cardioprotective signals are thought to be transmitted to mitochondria by specialized vesicular structures, signalosomes, which are assembled in caveolae and lipid rafts and contain various signaling molecules. We therefore performed a comprehensive characterization of ischemia‐induced caveolin‐enriched fractions (ICEF) in mitochondria preparations from Langendorff‐perfused hearts from WT and PDE3B KO mice before/after ischemia, using a combination of subcellular fractionation and isobaric tag for relative and absolute quantitation (iTRAQ). More than 500 ICEF proteins were identified; most of them were mitochondrial. Identified proteins were grouped according to their differential expression: i) no changes before/after ischemia and no differences in wild type and KO hearts, ii) changes after ischemia in both wild type and KO hearts, iii) changes after ischemia only in wild type hearts, and iv) changes after ischemia only in KO hearts. Furthermore, fractions containing the signalosomes were enriched in connexin 43‐containing mitochondrial populations, i.e. subsarcolemmal mitochondria (SSM), not interfibrillar mitochondria (IFM).In conclusion, these data suggest that targeted inactivation of Pde3b modifies composition of signalosomes associated with SSM to exert cardioprotective effects during I/R, and that PDE3B‐selective inhibitors might provide useful therapeutics to limit I/R injury.
HIV‐1 Env can pseudotype HTLV‐I and provide envelope‐mediated protection against super‐infection
Authors: Klase Zachary Alan , Jeang Kuan‐Teh 
Published: June 2021

Superinfection exclusion is the phenomenon whereby a virus infected cell becomes resistant to subsequent re‐infection with the same or a related virus. Human Immunodeficiency Virus (HIV) is one of the many viruses for which superinfection exclusion has been demonstrated. Three HIV proteins (Nef, Vpu and Env) have been implicated in mediating the effect; however, the mechanism of resistance has not been well described. Here we demonstrate that the HIV‐1 envelope protein (Env) when over‐expressed is sufficient to mediate superinfection exclusion. The mechanism appears to work at the cell surface CD4 receptor and is independent of CD4 down‐regulation and does not appear to involve either the CCR5 or the CXCR4 co‐receptor. These results challenge the assumption that down regulation of the CD4 receptor during infection is critical in preventing super infection. As an extension to our study, we have demonstrated that the Human T‐Cell Leukemia Virus (HTLV) can be pseudotyped using HIV Env. We have developed a replication competent HTLV‐1 virus that expresses the HIV‐1 (in place of the HTLV‐1) Env protein. With this chimeric virus, we plan to transduce CD4+ human T cells and demonstrate that these cells can be protected from HIV‐1 superinfection.This research was supported by NIAID intramural funds and a GCE phase 1 award from The Bill and Melinda Gates Foundation.
Structure‐activity optimization of 4H‐pyridopyrimidines: a class of selective bacterial protein synthesis inhibitors
Authors: Bullard James M , Guiles Joseph W. , Toro Andras , Ochsner Urs 
Published: June 2021

IntroductionBacterial protein synthesis is the target for numerous natural and synthetic antibacterial agents. Previous screening of a focused chemical compound library using a polyU mRNA‐directed aminoacylation/translation protein synthesis system from Escherichia coli yielded a lead series of compounds that inhibit protein synthesis with IC50's ranging from 3 to14 μM (Ribble, et. al. (2010) AAC, 54, 4648–4657). This series of compounds all contained the same central scaffold composed of tetrahydropyrido[4,3‐d]pyrimidin‐4‐ol (e.g. 4H‐pyridopyrimidine). These compounds inhibited bacterial growth with minimum inhibitory concentrations (MICs) ranging from 0.25 to 32 μg/ml.ResultsOver 100 analogs of the initial compounds were designed and synthesized and assayed. In biochemical protein synthesis reactions nineteen of the compounds exhibited IC50 values less than 2.0 μM and seven less than 1.0 μM. These compounds were active against S. pneumoniae (MIC=2 μg/mL), H. influenzae (MIC=1 μg/mL), and M. catarrhalis (MIC≤0.12 μg/mL) and S. aureus (4= μg/ml). Macromolecular synthesis (MMS) assays in E. coli and S. aureus confirmed that antibacterial activity resulted from specific inhibition of protein synthesis.ConclusionOptimization of 4H‐pyridopyrimidines yields potent inhibitors of protein synthesis with good activity against respiratory pathogens.
The Association Between Food Insecurity And Gait Speed Varied By Smoking Status In Older Adults
Authors: Xu Beibei , Zizza Claire 
Published: June 2021

Very few studies have examined the association between food insecurity and physical performance among older adults. Using data from the 1999–2002 National Health and Nutrition Examination Survey, we examined the association between food security and a performance‐based measure, gait speed, in 3,144 older adults (≥ 50 y). Participants were categorized by the US Food Security Survey Module and gait speed (m/s) was calculated as the walking distance (20 ft = 6.15 m) divided by time (s). Multiple linear regression models controlling for age, gender, race/ethnicity, education and income were used. The association between food insecurity and gait speed varied by smoking status (P = 0.005). For non‐smokers, those who were marginally food secure (β = −0.13, P = 0.016) and food insecure (β = −0.10, P = 0.004) had significantly slower gait speeds than food secure participants. No statistically significant associations were observed among current and former smokers. Finding no association among current and former smokers may be a result of poor physical performance among the referent group, food secure participants who smoke.Grant Funding Source: Alabama Agricultural Experiment Station (ALA013‐020)
Effectiveness of dietitian‐led diabetes management program on glycemic and diet control after a 2 year intervention in primary care in Taiwan
Authors: Sung Yi‐ching , Lin Chia Hui , Pai Hsiu‐hua , Hsu Chih‐Cheng , Shin Shyi Jang , Huang Meng‐Chuan 
Published: June 2021

ObjectiveThe aim of this study was to evaluate effectiveness of dietitian‐led diabetes management program on glycemic and diet control after a 2 year intervention in primary care clinics in Taiwan.MethodsAt baseline, we randomly assigned adult patients with type 2 diabetes to a routine care control (n=75) or a dietitian‐led intervention group (n=79) receiving diabetic self‐management education every 3 months.ResultsAfter 2 year intervention, completion rates were 77% (control: n=43; intervention: n=48). Hemoglobin (HbA1c %) were significantly different between baseline and 2 year only in intervention patients with baseline HbA1c ¡Ù7%, changes of HbA1c also correlated significantly (r=0.365, p=0.016) with carbohydrate intake. However, HbA1c did not improve significantly in control subjects regardless of entry HbA1c levels.ConclusionOn‐site dietitian‐led management of diabetes can improve glycemic control in patients with poorly managed type 2 diabetes in primary care setting in Taiwan.
Case Control Study for the Evaluation of Beneficial Effect(s) of Pistachio Nut Intake on Cardiovascular Risk Factors in Asian Indians with the Metabolic Syndrome
Authors: Gulati Seema , Misra Anoop 
Published: June 2021

BackgroundThe metabolic syndrome is precursor of diabetes and coronary heart disease. Previous studies have suggested that nut consumption leads to improvement in risk factors of the metabolic syndrome. Pistachio nuts are easily available and frequently consumed by general population.ObjectiveTo determine whether substituting 15% and 20% of the daily caloric intake in the form of pistachio nuts improves the risk factors of the metabolic syndrome among Asian Indians.DesignRandomized case control design.SettingOutpatient dietary modification, counseling and blood analysis.PatientsSixty patients with the metabolic syndrome.MethodsThe intervention duration was of 24 weeks preceded by a diet and exercise run‐in period of 30 days. For initial 12 weeks subjects in case group were given basic diet plus pistachio nuts constituting 15% of daily calorie intake. Subsequently, dosage of pistachio was increased to 20% of the total calorie intake for another 12 weeks. Controls were given equi‐calorie, high fiber low fat diet. All the subjects in cases and controls were followed for 6 months. At the end of the study, comparative analysis was done between cases (who consumed pistachio nuts) and controls for anthropometry and measures of obesity, measures of glycemia, anti‐inflammatory markers and markers of oxidative stress.ResultsResults would be presented after analyzing the data.ConclusionsResults are awaited.
Environmental change program associated with relative decrease in frequency of carryout/fast food consumption among African American caregivers
Authors: Cessnun Kathryn , Dennisuk Lauren , Coutinho Anastasia , Sharma Sangita , Shin Ahyoung , Christiansen Karina , Yong Rachel , Lwin Julia , Gittelsohn Joel 
Published: June 2021

Low‐income African American families in Baltimore City live in neighborhoods with limited access to healthy foods. The Baltimore Healthy Eating Zones (BHEZ) study aimed to improve diet quality among adolescents and their caregivers through an environmental intervention that involved peer mentoring, cooking demonstrations, taste tests, point‐of‐sale marketing and promotional giveaways at recreation centers and corner stores over a 9 month intervention period. Caregiver and child dyads (n=242) from 7 control and 7 intervention sites were interviewed before and after the intervention and asked about their monthly food purchases from carry out and fast food restaurants. Changes in the frequency of these food purchases were analyzed using a Wilcoxan Signed Ranks Test. The frequency of food purchases by caregivers from carry out and fast food restaurants significantly increased from 1.50±2.18 to 3.88±4.99 times per month among the control group (p=0.037) but did not significantly change from 8.67±10.06 to 6.12±8.70 times per month in the intervention group (p=0.119). These preliminary findings suggest that an environmental intervention like the BHEZ program may be an effective approach for improving the food purchasing behaviors of adult African American caregivers.Grant Funding Source: The Robert Wood Johnson Foundation
Lifestyle barriers to managing hypertension in people of African descent
Authors: Lancaster Kristie J , Midberry Sara A , Watts Sheldon O , Cole Helen V , Schoenthaler Antoinette M , Ogedegbe Gbenga 
Published: June 2021

PurposeTo determine the lifestyle behaviors that act as barriers to controlling blood pressure among a sample of hypertensive persons of African descent.MethodsA total of 25 people of African descent diagnosed with hypertension (HTN) were recruited at 3 churches, one African American (AA, N=10), one African immigrant (AI, N=7), and one predominantly West Indian (WI, N=8). A Nominal Group Technique (NGT) focus group session was held at each church. Each group generated a list of responses to the question: “What are some things that make it hard for people to follow lifestyle recommendations to take care of their high blood pressure?” Participants then ranked their top responses, and the rankings were summed. The 10 responses with the highest scores were then given a rating of 0 to 10 by participants and the ratings were summed.ResultsThe WI group was older, had less education, and had had HTN for longer. The AI group was the youngest, had the most education, and had HTN for the shortest time. The AA & WI groups rated stress, physical limitations to exercise, and weight maintenance in their top 5 barriers. The AI group rated time for exercise, work, and eating habits in their top 5.ConclusionsThis study suggests groups of African descent may have different lifestyle barriers to managing HTN. Future work should examine the need for tailoring intervention by ethnic group. Funded by NHLBI.
Fish oil increases tumor associated T regulatory cells in experimentally induced colitis
Authors: Gurzell Eric A , Rondini Elizabeth A , Fenton Jenifer I 
Published: June 2021

Our laboratory recently reported the unexpected observation that feeding fish oil enriched with docosahexaenoic acid (DFO) exacerbated colitis and colonic dysplasia in SMAD3−/− mice. These effects were associated with reduced T cell populations in secondary lymphoid tissue. The objective of this study was to determine the effect of DFO on immune cell populations and markers of inflammation at the local site of inflammation/dysplasia by immunohistochemistry. Mice were fed AIN‐93G diets modified to include corn oil (CO), safflower oil (SF), or DFO (0.75–6.00%) as the fatty acid source for 8 wks, gavaged with H. hepaticus to induce colitis, then sacrificed 4 wks post‐infection. We found significant differences between dietary treatments for multiple T cell markers in the proximal colon. Compared to controls, total T lymphocytes as well as FoxP3 positive cells were more prominent in the 3.75 and 6% DFO diets, which corresponded with the highest colitis scores. Staining for iNOS and COX‐2, markers associated with colon carcinogenesis, did not differ across treatments. These data suggest that DFO promotes an immunosuppressive environment at the tumor site with strong direction by T regulatory cells, shifting from a Th1 type to Th2 type immune response. The observed changes in immune cell populations and suppressed cell‐mediated immunity may begin to explain the exacerbated colitis.Grant Funding Source: n/a
Associations of the thymidylate synthase 3¡¦UTR polymorphisms with one carbon status, lymphocytic p53 oxidative lesions and hepatocellular carcinoma progression
Authors: Kuo Chang Sheng , Hwung Chyi‐Yun , Kuo Shine‐Tou , Lin Ching‐Yih , Cheng Chin‐Pao , Chen Chien‐Hung , Yang Feili Lao , Huang Rwei‐Fen Syu 
Published: June 2021

The aims of the study were to investigate relationships between thymidylate synthase (TS) 3'UTR polymorphisms. Genotypes in a 6‐bp deletion/insertion in the 3’‐untranslated region (TS 3'UTR), blood folate and homocysteine (Hcy) levels were determined on 232 HCC patients. The frequencies of TS 3’‐UTR genotype of the study HCC patients were 52% (del6/del6), 43% in del6/ins6, and 5% in ins6/ins6. Increased frequencies of one 6‐bp insertion in the TS genotypes were associated with decreased Hcy levels (r = −0.154, P = 0.04). Compared with the (del6/del6) variant, HCC patients with at least one 6‐bp insertion variants had lower levels of AFP tumour marker (P = 0.05). Among individuals with low serum folate levels (< 14 nM), the TS del6/ins6 and ins6/ins6 variants had significantly lower levels of p53 promoter oxidative damage than the del6/del6 variant. After adjustment for multiple factors including life‐style, clinical factors and serum folate status, the odds ratios for developing large tumour (size > 3 cm) were 0.24 (95% CI: 0.07–0.08) for combined MTHR C677T mutant variants (CT+TT genotypes) and TS 3'UTR mutant variants (del6/ins6 + ins6/ins6) compared with wild type variants. This protective effect against developing large tumour was negated after further adjustment of lymphocytic p53 oxidative lesions. Taken together, our data suggested that HCC patients carrying combined genotypes with at least one mutant allele in MTHFR C677T and TS 3'UTR 6 bp‐insertion variants have reduced risks of developing large tumour, which may be mediated by amelioration of p53 oxidative lesions.Grant Funding Source: Department of Health in Taiwan
GP‐1 induces autophagy of human colorectal cancer cells by inhibiting AKT/mTOR and activating type III PI3K/beclin 1 signaling pathways
Authors: Su Chun‐Li , Yen Cheng‐Hsin , Lin Chun‐Nan , Jiang‐Shieh Ya‐Fen , Won Shen‐Jeu 
Published: June 2021

GP‐1, a pure compound isolated from the pericarp of Garcinia subelliptica, is a traditional remedy which exhibits anti‐oxidative, anti‐inflammatory, and anti‐tumor effects. Our unpublished data indicate that GP‐1 induced apoptosis of human colorectal cancer HT‐29 cells via caspase‐ and mitochondria‐related pathways. Here we report that GP‐1 also induced autophagy of the cells characterized by formation of acidic vesicular organelles using flow cytometry, expression of autophagic marker LC3‐II using immunoblotting and confocal microscopy, and accumulation of autophagic vacuoles using transmission electron microscopy. In the GP‐1‐treated cells, the expression of p‐AKT, p‐mTOR, and p‐p70S6k was decreased but that of type III PI3K, becline 1, and Atg5‐Arg12 was increased. Pre‐treatment of the cells with autophagy inhibitor 3‐methyladenine or general caspase inhibitor Z‐VAD‐FMK respectively reduced GP‐1‐induced apoptosis or autophagy using annexin V‐FITC and propidium iodine double staining or acridine orange staining followed by flow cytometry. These findings describe the molecular actions of GP‐1 in HT‐29 cells and reveal the enhancement of apoptosis by autophagy, and vice versa.(Supported in part by National Science Council, Taipei, Taiwan, No. NSC 95‐2313‐B‐309‐001 and NSC 96‐2313‐B‐309‐001‐MY2).