bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uniquely human changes in expression and binding specificity of Siglec‐11: implications for human brain evolution (787.2)
Authors: Schwarz Flavio , Deng Lingquan , Landig Corinna , Varki Nissi , Varki Ajit 
Published: June 2021

We are exploring the role of Siglec‐11, a member of the sialic acid‐recognizing immunoglobulin‐like lectin family, in the modulation of microglial functions in the human brain. Human SIGLEC11 underwent two tandem and likely simultaneous gene conversions by the adjacent pseudogene SIGLEC16P (Wang et al., Mol. Biol. Evol., 29:2073‐2086, 2012). These genes conversions preserved an intact open reading frame, but changed 5' untranslated sequences, likely altering transcription of SIGLEC11. Using specific antibodies, we confirmed the resulting uniquely human expression of Siglec‐11 in brain microglia, and next wished to define its ligands. Surprisingly, we did not observe robust binding of human Siglec‐11 to any sialic acid‐containing glycan in multiple assay platforms. In contrast chimpanzee Siglec‐11 strongly recognized several glycans terminating with sialic acid, with a preference for the non‐human sialic acid N‐glycolylneuraminic acid (Neu5Gc). Accordingly, chimp Siglec‐11 bound to cells proportionally to their Neu5Gc content, but human Siglec‐11 exhibited minimal binding to the same cells. We also found that human Siglec‐11 binds to a microglial cell line independently of sialic acid, and are characterizing the nature of this ligand. Alterations in the expression pattern and ligand‐binding specificity of human Siglec‐11 may have evolved to generate novel, human‐specific functions in the brain.Grant Funding Source: Supported by P01 HL057345
Hyperglycemia affects the glycophenotype and the growth of colon carcinoma cells in vivo (789.2)
Authors: Vasconcelos‐dos‐Santos Andreia , Mantuano Natalia , Loponte Hector , Oliveira Isadora , Moll Fernanda , Dias Wagner , Todeschini Adriane 
Published: June 2021

Cancer cells depend on altered metabolism and nutrient uptake to generate and keep the malignant phenotype. Recent work suggests that the metabolite availability to the hexosamine and Golgi O‐glycosylation pathways exerts control over cell signaling, gene expression and cell migration (Alisson‐Silva etal., Plos One, 8: e60471, 2013). Indeed, high glucose concentration increases O‐glycosylation of FN (onFN), which generates the onfFN, and modulates tumorogenesis. Herein we implicate hiperglycemia in facilitating cancer progression and increasing onFN expression in vivo. Cells from colon carcinoma of C57BL/6 mice (MC‐38 cell line) were subcutaneously inoculated in streptozotocin (STZ)‐treated or untreated C57BL/6 mice. Subcutaneous tumors from STZ‐treated group were higher and more vascularized when compared with vehicle group. Tumors from STZ‐treated mice presented high expression of alpha2‐6‐Neu5Ac and alpha1‐3‐/ alpha1‐6‐Fucose (Fuc) containing glycoconjugates as well as increased expression of onFN. These data suggest that metabolite availability modulates cell surface glycosylation contributing to tumor formation and progression.Grant Funding Source: Supported by CNPq, FAPERJ and CAPES
Nonencapsulated group A Streptococcus associated with human invasive disease (790.1)
Authors: Henningham Anna , Yamaguchi Masaya , Aziz Ramy , Kuipers Kirsten , Dahesh Samira , Yamaguchi Yuka , Seymour Lisa , Ben Zakour Nouri , He Lingjun , Smith Helen , Grimwood Keith , Beatson Scott , Walker Mark , Nizet Victor , Cole Jason 
Published: June 2021

Group A Streptococcus (GAS) is a leading human pathogen, causing 650,000 severe invasive diseases annually with 25% mortality. M1 GAS is the most frequently isolated serotype from invasive disease worldwide; however, a recent occurrence of invasive infections in Australia was attributed to M4 GAS. Here, we use a combined molecular genetics and bioinformatics approach to characterize 17 clinical M4 isolates associated with this invasive disease episode. The M4 isolates were classified into 3 pulsed‐field gel electrophoresis groups, and 2 multilocus sequence types. All isolates lacked hyaluronic acid (HA) capsule, a major antiphagocytic virulence factor, and whole genome sequence analysis of 2 isolates revealed the complete absence of the hasABC capsule biosynthesis operon. Most isolates contained mutations within the covRS two‐component regulator, a hallmark of hyperinvasive GAS. Transformation of a plasmid expressing hasABC into M4 GAS restored capsule production. However, encapsulation neither promoted survival in whole human blood, nor enhanced virulence of wild‐type M4 GAS in a mouse model of systemic infection. Bioinformatic analysis found no hasABC homologs in closely related species, suggesting that this operon was a recent acquisition by ancestral GAS. Together, these data demonstrate that nonencapsulated GAS is capable of causing life‐threatening invasive human infections.Grant Funding Source: National Health and Medical Research Council of Australia; National Institutes of Health
Novel EGFR inhibitors attenuate Ang II‐induced cardiac hypertrophy (794.3)
Authors: Peng Kesong , Pan Yong , Liang Guang 
Published: June 2021

Background: Cardiac hypertrophy is a multiple response to physiological and pathological stimuli and an important risk factor for heart failure. The aim of this current study was to examine the effect of EGFR inhibitors on Ang II‐induced cardiac hypertrophy and further identify the underlying cellular/molecular mechanisms in Ang II/EGFR‐involved cardiac hypertrophy pathway. Methods: In vitro cultured rat H9C2 cells were induced hypertrophy by AngII. C57BL/6 mice were given a subcutaneous injection of AngII for two weeks and simultaneously were treated with EGFR inhibitors by daily gavage. Result: Stimulation of either Ang II or EGF significantly activated EGFR pathway and increased EGFR, AKT and ERK phosphorylation, while these increases were dose‐dependently inhibited by EGFR inhibitors. In the meantime, EGFR inhibitors attenuated Ang II‐mediated cardiac hypertrophy. Oral administration with small molecule EGFR inhibitors also decreased the cardiac hypertrophy and dysfuncti on in Ang II‐treated mice. Finally, the results showed that Ang II‐induced EGFR activation was mediated by Src phosphorylation. Conclusion: EGFR plays an important role in Ang II‐induced cardiac hypertrophy in vitro and in vivo, and inhibition of EGFR by specific molecules may be an effective strategy for the treatment of Ang II‐associated cardiac diseases.Grant Funding Source: China national science foundation
Estrogen mediated regulation of TGFβ pathway signaling in cardiac hypertrophy (795.4)
Authors: Malone Payton , Burton Tyler 
Published: June 2021

It is well documented that pre‐menopausal women are protected from heart disease, in part through the effects of estrogen. It has been established that estrogen treatment prevents cardiomyocyte hypertrophy and that estrogen attenuates the prohypertrophy TGFBeta (TGFb) signaling family. However, it has yet to be established whether estrogen is in part mediating its cardioprotective effects via the silencing of TGFb signaling. To address the differential control of the TGFb family member expression in female vs. male mice in the setting of cardiac hypertrophy, we performed transaortic constriction (TAC) to induce hypertrophy. We then analyzed gene and miRNA expression for TGFb family members and potential targeting miRNAs, several of which are known to be induced by estrogen. Next Generation Sequencing was performed to establish miRNA profiles in male and female following the TAC. Differential expression of TGFb targeting miRNAs was confirmed by TaqMan assays. TaqMan also revealed that many of the TGFb family members were preferentially downregulated in female TAC mice as compared to age matched male TAC mice. To define the mechanisms by which estrogen regulates TGFb expression we are performing a series of estrogen receptor activation studies in an in vitro cardiomyocyte hypertrophy model system. Preliminary results show distinct activation of TGFb family members and targeting miRNAs in the traditional nuclear receptors. The direct role for estrogen‐induced miRNAs will be further investigated using antagomirs in vitro. These data taken together will define the underlying estrogen mediated pathways related to TGFb signaling and could lead to new therapeutic targets for heart disease.Grant Funding Source: Supported by an Institutional Development Award (IDeA) under grant number R15HL108192
Combination of ouabain and a specific ROCK inhibitor Y27632 in HeLa cells: implication of therapeutic benefits (797.2)
Authors: Ibisoglu Burcin , Simay Yaprak , Ozdemir Aysun , Ark Mustafa 
Published: June 2021

In our previous work we have observed that while the concentrations of ouabain above 100 nM had cytotoxic effects and 30 nM ouabain induced senescence in HeLa cells, ouabain had no noticeable morphological effects on cells at 10 nM and lower concentrations. Therefore in the current work we evaluated the effect of 10nM ouabain on the migration of HeLa cells and the possible involvement of ROCK in this process. The xCELLigence RTCA DP system with CIM‐plates was performed to detect the effect of drugs on cell migration. HeLa cells were exposed to 10 µM Y27632 for 30 min and 0.5 µg/ml CT04 (Rho A inhibitor) for 2h. After preincubation cells were treated with 10 nM ouabain. Cell index was monitored every 15 min for up to 48 h. Our results showed that while 10 nM ouabain had no inhibitory effect on cell migration, combination of ouabain with Y27632 significantly reduced the migrated cell number of HeLa cells. Also Y27632 incubation by itself inhibited the migration of cells. Moreover similar results obtained from CT04 treatment. In contrast with data reported that ouabain has anti migratory properties at nanomolar concentrations, we demonstrated that low nanomolar concentration of the cardiac glycoside did not inhibit the HeLa cell migration. It has been known that ROCK inhibitors have some anticancer properties. In addition, cardiac glycosides have been developed and tested in clinical trial for the treatment of cancer. Therefore our findings imply that combination therapy of ouabain and Y27632 may be beneficial for cancer patients.Grant Funding Source: This study is supported by TUBITAK in 110S426 project.
Loss of DNA cytosine methylation increases ethidium bromide resistance in Escherichia coli (800.4)
Authors: Mandarano Alexandra , Varechtchouk Olga , Simon Robert , Militello Kevin 
Published: June 2021

Loss of DNA cytosine methylation increases ethidium bromide resistance in Escherichia coli Alexandra H Mandarano, Olga Varechtchouk, Robert D Simon, Kevin T Militello. Biology, State University of New York at Geneseo, Geneseo, NY In E. coli, the second cytosine in the sequence 5’CC(A/T)GG3’ is methylated by the Dcm enzyme. The sugE gene, which codes for a membrane transporter, has one dcm recognition site in its 5’ flanking region, three in the open reading frame and one in the 3’ flanking region. We used qPCR to measure sugE RNA levels in wild‐type and dcm knockout cells. Our data demonstrate that the sugE gene is overexpressed at early stationary phase in dcm knockout cells. Expression of sugE also increased in the presence of the DNA methyltransferase inhibitor 5‐azacytidine. Furthermore, stationary phase sigma factor rpoS knockout cells showed significant decreases in sugE expression, which is consistent with a known inverse relationship between Dcm and RpoS expression. The sugE gene has been shown to confer resistance to quaternary ammonium compounds, and has been linked to ethidium bromide (EtBr) resistance. In order to determine if dcm influences the sensitivity to antibacterial compounds through changes in sugE expression, the sensitivity of wild‐type, dcm knockout, and sugE knockout strains was compared using Kirby‐Bauer disc diffusions assays, MIC assays and growth curve analyses. Our data indicate that sugE knockout cells are hypersensitive to EtBr, whereas dcm knockout cells have increased resistance to EtBr. We are continuing to investigate the effects of other drugs on these E. coli strains and aim to elucidate the mechanism of the effect of Dcm on SugE‐mediated drug resistance.Grant Funding Source: Geneseo Foundation
Disparate regulation of IGF‐1 in primary osteoblasts isolated from MAPK phosphatase‐1 knockout mice involves AKT/ β‐catenin pathway (802.18)
Authors: Datta Nabanita , Datta Tanuka , Mahalingam Chandrika , Chukkapalli Sahiti 
Published: June 2021

The role of MAPKs in osteogenesis and in Parathyroid hormone (PTH) signaling has been shown in vitro and in vivo previously. However, the role of MAPK phosphatase‐1 (MKP‐1) in bone formation remains unclear. We observed age dependent sexual dimorphism in bone phenotype of MKP‐1 knock out (KO) mice showing osteopenia in females and osteopetrosis in males. We investigate the involvement of MKP‐1 on b‐catenin, a key mediator of the canonical Wnt signaling pathway and an important regulator of bone forming cells, the osteoblasts. Signal transduction through b‐catenin requires inhibition of GSK‐3b which is also inhibited via phosphorylation by AKT upon insulin‐like growth factor‐1 (IGF‐1) signaling. Real‐time PCR analysis of primary calvarial osteoblasts revealed significant down‐regulation of IGF‐1 mRNA expression in osteoblasts isolated from MKP‐1 KO female mice in contrast to KO osteoblasts from males. Inhibition of P‐ERK and P‐p38 with pharmacological inhibitors showed disparate regulation of IGF‐1 expression in WT and KO male and female mice, suggesting MKP‐1/MAPK dependent regulation of IGF‐1. Immunobloting showed diminished AKT phosphorylation and b‐catenin expression in KO osteoblasts in the presence or absence of PTH. Taken together, our findings provide new insight into the role of MKP‐1 in IGF‐1/AKT/b‐catenin pathway in osteoblast which may be of potential biological and pathophysiological importance.Grant Funding Source: Supported by NIH DK087848 and WSU OVPR
The protein phosphatase isoforms PP1γ1 and PP1γ2 are non‐equivalent in supporting sperm function and male fertility (802.20)
Authors: Dudiki Tejasvi , Sinha Nilam , Kline Douglas , Vijayaraghavan Srinivasan 
Published: June 2021

Ser/Thr phosphatase type I isoforms PP1γ1 and PP1γ2 are alternately spliced transcripts of one gene, PPP1CC. Amino acid sequences of PP1γ1 and PP1γ2 are identical except at their extreme C‐termini. PP1γ1 is ubiquitous whereas PP1γ2 is abundant in testis. PPP1CC knockout male mice (‐/‐) are sterile due to impaired sperm morphogenesis. Fertility can be restored in PPP1CC (‐/‐) mice by testis specific transgenic expression of PP1γ2. The purpose of this study was to determine if PP1γ1 is equivalent to PP1γ2 in supporting spermatogenesis and male fertility. We generated four different transgenic rescue mice lines with cDNA containing the entire PP1γ1 coding sequence followed by various portions of its 3’UTR. Testis expression of PP1γ1 occurred only when the transgene lacked a 1Kb segment immediately following the stop codon of the PP1γ1 transcript. Levels of the PP1γ1 transgene in this line were comparable to PP1γ2 levels in PPP1CC (+/‐) testis. Spermatogenesis was restored in these PP1γ1 rescue mice, but males were sub‐fertile due to impaired sperm motility. Our studies suggest that PP1γ1 in mammals is excluded in differentiating spermatogenic cells due to alternate splicing and miRNA mediated instability of its transcript. Thus PP1γ2, the PP1 isoform in mammalian sperm, has isoform specific functions in supporting normal sperm motility and male fertility.Grant Funding Source: Supported by R15HD068971 and R15HD061869
Near‐infrared spectroscopy characterizes vitamin deficiencies and infection status during pregnancy (804.1)
Authors: Sanchez‐Galan Javier , Gonzalez‐Fernandez Doris , Murillo Enrique , Scott Marilyn , Burns David , Koski Kristine 
Published: June 2021

Background: Near‐infrared (NIR) spectroscopy can identify spectral changes resulting from viral infections but has not been used to examine vitamin deficiencies or infection status during pregnancy.Objectives: To determine if vitamin status (sufficient/deficient) for A, D, B12, and folate, and presence/absence of respiratory, skin, oral, urogenital infections were reflected in NIR of maternal serum in 2nd (n=90) and 3rd trimester (n=100) in rural Panama.Methods: Eight functional groups (1600‐2400nm) were selected (CH, SH, POH, ROH, amide, amine, lactate and glucose). Values for each functional group and their ratios were compared by trimester between mothers with/without each deficiency, and with/without each infection using Mann‐Whitney U‐test.Results: Serum profiles differed by vitamin status in the 2nd trimester for vitamins A (amide:lactate, amine:lactate, lactate:glucose), B12 (POH:amide, ROH:amide) and folate (CH:ROH, SH:ROH). Differences were also observed for oral (CH:SH) and respiratory (amine:glucose) infections. In the third trimester, differences with vitamin D status involved both glucose and amine whereas folic acid deficiency involved differences only in amine. Only lactate differed between women with and without respiratory infections.Conclusion: NIR spectroscopy identified spectral differences due to nutrient deficiencies and infections.Grant Funding Source: SENACYT, NSERC
Fast and efficient estimation of micronutrient intake in Brazil (804.16)
Authors: Biesalski Hans , Feuerstein Clarissa , Lambert Christine , Finco Fernanda 
Published: June 2021

A fast and efficient detection of micronutrient deficiencies is needed to fight Hidden Hunger, which causes numerous development disorders. In this work we developed a method of detecting micronutrient malnutrition, which is based on intake data of food groups, not on single foods. This facilitates data acquisition for interviewer and respondent as well as time management for data input. The focus is on accurate estimation of intake of the most misrepresented micronutrients in the Brazilian diet (iron, vitamin A, vitamin E, thiamin, calcium, folate).The Food groups were created from 24‐Hour Dietary Recalls on two non‐consecutive days of 34,003 Brazilian inhabitants, retrieved from the National Dietary Survey 2008‐2009. Traditional food groups, like vegetables or fruits, were refined by isolating food types that considerably bias the average nutrient amount of each group. This has been accomplished by considering population’s consumption variance and by using cluster analysis to isolate food types with an extreme deviating nutrient amount.As a result, 20 stable food groups were formed, based on their average food consumption and nutrient composition. The average nutrient amount was calculated for population subgroups defined by the 5 geographic regions of Brazil and four income groups.In conclusion, the program can help to uncover cases of malnutrition and facilitate actively the governmental efforts.
Urinary iodine and goiter in preschool children from the Amhara region, Ethiopia (804.23)
Authors: Gashu Dawd , Bougma Karim , Harding Kimberly , Samuel Aregash , Adish Abdulaziz , Desse Gulelat , Marquis Grace 
Published: June 2021

Iodine deficiency (ID) is highly prevalent in Ethiopia. As part of a salt iodization project, children (n=688) 54‐60 months of age were randomly selected from 26 districts of the Amhara region, Ethiopia. Anthropometry, urinary iodine (UI) and goiter were assessed and the presence of visible goiter in the family was queried between October, 2011‐March, 2012. Children’s nutritional status was categorized using WHO standards. UI was determined using the Sandell‐Kolthoff reaction. Goiter was assessed by palpation following the WHO/UNICEF/ICCIDD guidelines. Stunting (<‐2HAZ) was 43.2% while underweight (<‐2WAZ) was 29.9 %. The median UI was 11.4 µg/L and varied widely by district (0‐286 µg/L). Individual values ranged from 0‐502 µg/L. Overall, 20.9 % of children had visible goiter and 23 % had palpable goiter, with variation by district in total goiter rate from 5‐79%. Goiter prevalence was significantly higher in children with visible goiter in the family than in children from families without visible goiter. Median UI was higher (p=0.001) in children from families without visible goiter than from families with visible goiter (20 vs. 4.1 µg/L), respectively. Our data illustrate the severity of ID in Amhara region and the need for rapid and complete implementation of salt iodization. The wide variation in goiter prevalence and UI among districts emphasizes the importance of both national and local monitoring programsGrant Funding Source: Funded by Micronutrient Initiative and The German Academic Exchange Service
Food iron fortification, high meat intake and HFE gene in a healthy adult male population from Argentina (804.25)
Authors: Airaldi Romina , Castro Marcelo , Sebastiano Vanesa , Donadío Luján , Budetti Cecilia , Rey Jorge , Lardo Marta , Fleischman Silvana , Felipoff Ana , Langini Silvia 
Published: June 2021

Wheat flour fortification with iron (Fe) is mandatory in Argentina since 2002, although feeding habits are characterized by high bovine meat intake‐ (54.1 kg/per capita/y, FAO 2009). To estimate heme and nonheme Fe intake, 87 male blood donors (19‐65 y) attending the Hospital de Clínicas, Universidad de Buenos Aires, Argentina, (2012‐2013) were enrolled in the study. A 135‐item food‐frequency questionnaire including bovine meat, poultry, fish, pork, processed meat, cereal products and bakery products prepared with wheat flour fortified with Fe (30 mg Fe/Kg) was administered. Daily Fe intake was calculated according to ARGENFOODS and USDA National Nutrient Database on Standard Reference. Genotyping for the C282Y, H63D and S65C mutations in the HFE gene was performed (PCR‐RFLP) in samples (n=40) collected with EDTA. Dietary Fe intake (mg/d) was: Mean ± SD (range): Total Fe (T): 24.2±12.5 (8.9‐63); Heme Fe (H): 2.26±1.45 (0.00‐6.84); Nonheme Fe (NonH): 22± 11.8 (7.4 ‐59.8); Fe‐fortified wheat flour (Fe‐WF): 10.5 ±6.9 (2.6‐44). Fe intake was higher (111% ‐ 788%) than RDA (8 mg/d, FNB); Fe‐WF was 47.7% of NonH. Heterozygosity and homozygosity for H63D mutation was 15% and 2.5%, respectively; C282Y nor S65C occurred. These preliminary results alert about potential diet‐related effects of Fe accumulation in a population most probably unaware of any family history of Fe overload.Grant Funding Source: Supported by Universidad de Buenos Aires 20720120200004BA, Argentina
Retinol and tocopherol status in pulmonary tuberculosis patients in the country of Georgia (804.29)
Authors: Jones Jennifer , Frediani Jennifer , Tukvadze Nestan , Kipiani Maia , Sanikidze Eka , Hebbar Gautam , Booth Sarah , Blumberg Henry , Tangpricha Vin , Ziegler Thomas 
Published: June 2021

Objective: Evaluate serial plasma retinol and tocopherol levels in adults with new pulmonary tuberculosis (TB) in Tbilisi, Georgia.Methods: 129 subjects with pulmonary TB disease were enrolled in a randomized, controlled trial of high‐dose vitamin D3 (D3) + anti‐TB drugs. Plasma retinol, α‐tocopherol, and γ‐tocopherol were measured by HPLC (baseline, wks 8 and 16). Household contacts of TB subjects were baseline controls. Descriptive statistics (mean ± SD) and repeated measures ANOVA were used.Results: TB subjects exhibited significantly lower baseline plasma retinol (33.3 ± 11.7 vs. 58.8 ± 17.7 µg/dL; p < 0.001) and γ‐tocopherol (33.6 ± 15.6 vs. 40.8 ± 15.5 µg/dL; p = 0.02) levels vs. controls; α‐tocopherol levels were similar. D3 administration did not affect nutrient levels over time. Pooled data in all TB subjects revealed an increase in retinol levels over time (baseline to wk 16, +22%; p < 0.001). Levels of γ‐tocopherol rose at wk 8 (+11%; p < 0.001) but declined to baseline by wk 16. In contrast, α‐tocopherol fell by 9% at wk 16 vs. baseline (p < 0.01). Subjects with a BMI < 18.5 (n = 19), exhibited lower α‐tocopherol levels at wk 16 vs. baseline and wk 8 values (p = .003).Conclusions: Plasma retinol and tocopherol levels were lower in subjects with TB disease vs. uninfected household contacts. During anti‐TB treatment, plasma retinol increased and α‐tocopherol decreased, particularly in the more malnourished patients.Grant Funding Source: Supported by NIH K24 DK096574 and Emory Global Health Institute