bluuebunny/crossref_metadata_2025_split huggingface dataset:
The omega 3‐6 balance in foods predicts 3:6 proportions in tissue HUFA (605.9)
Authors: Lands Bill 
Published: June 2021

Objective: Many chronic health disorders are unintended results of eating foods with imbalanced amounts of n‐3 and n‐6 essential fatty acids (EFA) that accumulate in tissues as highly unsaturated fatty acids (HUFA) and lead to excessive chronic actions by n‐6 eicosanoids. To help people prevent chronic tissue imbalances, we made a simple tool to predict the impact of a food item on tissue HUFA.Methods: An empirical equation successfully predicts the quantitative impact of nutrient EFA on tissue HUFA proportions. Using it with data from the USDA Nutrient Database for eleven n‐3 and n‐6 nutrients in terms of 3‐6 differences led to Omega 3‐6 Balance Scores for over 5,000 foods (Lands B, Lamoreaux E. Nutrition &amp; Metabolism 2012; 9:46‐54). The Score is a single number that gives the likely impact of a food on the proportions of n‐3 or n‐6 acids which will develop in the HUFA of a person’s finger‐tip blood sample.Results: Foods with more positive 3‐6 Balance Scores raise the % omega‐3 in HUFA, whereas those with more negative Scores raise the % omega‐6. Calorie‐weighted average daily Scores for ethnic food styles worldwide range from +3 to ‐7. The 3‐6 Balance Scores at the public website http://www.fastlearner.org/Omega3‐6BalanceApp.htm can be downloaded to mobile devices to help guide personal food choices when shopping, preparing meals or discussing foods with friends. Examples are: broccoli, +3; mackerel, +52; flax oil,+46; potato, 0; rice, 0; salmon, +46; spinach,+5; avocado, ‐10; hummus, ‐ 16; peanut butter, ‐19; potato chips, ‐ 22; tofu, ‐26; vegetable oil (corn, ‐59; soybean, ‐50); walnuts, ‐44.Conclusions: Explicit Scores replace vague, general advice to eat “healthy meals”. To lower the risk for diseases mediated by n‐6 eicosanoids, people can select more positive Scores as they “NIX the 6 and EAT the 3”. Effective health care works better when preventing the cause rather than just treating symptoms created by the cause.
Overcoming blood‐brain barrier by targeted drug delivery to brain tumor vasculature with carbohydrate mimetic peptide in mouse glioma model (607.13)
Authors: Suzuki‐Anekoji Misa , Yeh Jiunn‐Chern , Nonaka Motohiro , Shibata Toshiaki , Nakayama Jun , Akama Tomoya , Sugihara Kazuhiro , Fukuda Minoru , Fukuda Michiko 
Published: June 2021

Although glioma cells cultured in vitro are responsive to several anti‐cancer drugs, it is very difficult to treat glioma in vivo due to blood‐brain barrier (BBB). In the previous study, we identified a carbohydrate mimetic peptide, designated as IF7, that homes tumor vasculature. IF7 binds to annexin A1, which is expressed specifically on the endothelial cell surface of malignant tumors. We showed that IF7 conjugated anti‐cancer drug SN38 (IF7‐SN38) suppressed growth of colon, melanoma, breast, prostate and lung tumor models in the mouse. Since IF7 was thought to be transported across endothelial cells through transcytotic pathway, we hypothesized that IF7 can deliver anti‐cancer drug to brain stroma overcoming BBB.In this study, we produced glioma tumors in mouse brains by intracranial injection of C6 cells. To determine targeting of IF7 peptide, Alexa 488‐tagged IF7 (IF7‐A488) was injected intravenously. IF7‐A488 targeted tumor vasculature within minutes, penetrated through endothelial cell wall and spread to the glioma sphere, while control peptide conjugate did not. We injected luciferase‐expressing C6 (C6‐Luc) cells into mosue brains, and monitored growth of C6‐Luc tumor by Xenogen IVIS imager. Daily intravenous injection of IF7‐SN38 reduced size of C6‐Luc glioma with minimum effective dose at 2.7 µmoles/kg, which is 15 times lower than reported dose of SN38. To compare targeting efficacy of IF7‐SN38 between brain tumor and subcutaneous tumor, two B16‐Luc tumors, one in the brain and another under the skin, were generated in a mouse. Intravenous injection of IF7‐SN38 suppressed growth of these tumors with comparable efficiency regardless of their locations at concentration of 5 µmoles/kg, while unconjugated SN38 suppressed growth of only subcutaneous tumor at 50 µmoles/kg but not the brain tumor, demonstrating the efficacy of IF7‐SN38 in overcoming BBB.These results strongly encourage clinical application of IF7‐SN38 to glioma tumors.Grant Funding Source: Supported by NIH grant CA33859
SLC2A11 (GLUT11) as mannose preferential transporter (607.15)
Authors: Ichikawa Mie , Losfeld Marie‐Estelle , Freeze Hudson 
Published: June 2021

Most studies of hexose transporters (GLUT family) focus on glucose and fructose import for energy generation. Few studies examine their role in delivering sugars for biosynthetic pathways. Exogenous mannose can directly contribute nearly 50% of the mannose found in glycoproteins, even though its extracellular concentration (50 µM) is 100‐fold lower than physiological glucose (5mM). To explain this preference, we hypothesized the existence of a high affinity mannose‐preferential hexose transporter. We identified a patient with damaging mutation in SLC2A11 (Glucose transporter, GLUT11) and applied our new GC‐MS method to determine the contributions of 13C‐glucose and 13C‐mannose to N‐glycans. Patient fibroblasts showed reduced direct contribution of mannose, prompting us to investigate GLUT 11 as potential mannose transporter. RNAi knockdown of GLUT11 confirmed that it directly contributes mannose to N‐glycans , especially at the physiological range (50 µM) suggesting that GLUT11 has low Kuptake for mannose. The reported Km for glucose is 160µM. Preliminary results show that knockdown of GLUT 1 has no effect on mannose flux into N‐glycans. We suggest that GLUT11 is the first mannose‐preferential transporter for N‐glycan synthesis. Other mannose preferential transporters may exist.Grant Funding Source: R01DK55615 and The Rocket Fund
How gene knockouts perturb the N‐glycome of Caenorhabditis elegans (608.3)
Authors: Wilson Iain , Yan Shi , Paschinger Katharina 
Published: June 2021

Although the model nematode Caenorhabditis elegans is considered to be rather simple, its N‐glycome proves to be one of the more complex amongst lower multicellular eukaryotes. Indeed, the number of types and the unusual structure of N‐glycans in this organism seemingly outmatches that of plants or insects. Underlying this is a wealth of glycosyltransferases; as judged by homology, there are well over twenty fucosyltransferases encoded by the worm genome, but the biochemical functionality of only a minority has been assigned. Glycomic analyses would suggest that at least five fucosyltransferases act on N‐glycans of the nematode: beyond the ‘typical’ core α1,3‐ and core α1,6‐fucosyltransferases modifying the distal core N‐acetylglucosamine residue, one fucosyltransferase transfers to the proximal residue of the core, at least one to the periphery of paucimannosidic glycans and at least one to the ‘Galβ1,4Fuc’ epitope. Furthermore, N‐acetylglucosaminyltransferases, processing hexosaminidases and Golgi mannosidase II play an important role in shaping the final N‐glycome. Using a mix of typical assays, glycan microarrays and glycomic analyses of knock‐out strains, we have determined the biochemical function of a number of relevant enzymes. It is also remarkable how novel structures become apparent when analysing the glycomes of ‘multiple‐knock‐out’ strains. Thus, at least under laboratory conditions, a high degree of plasticity of the worm glycome is possible.Grant Funding Source: Austrian Science Fund (FWF) and European Commission (Euroglycanarrays ITN)
IR‐induced phosphorylation of rpS3 and TRAF2 regulates radioresistance in non‐small cell lung cancer cells (609.1)
Authors: Kim EunGi , Kwon TaeWoo , Son Beomseok , Lee Jongbong , Youn BuHyun , Lee Jung Sub 
Published: June 2021

Radioresistance is a main impediment to effective radiotherapy. However, the exact molecular mechanism of radioresistance has not been understood yet. To elucidate the mechanism in lung cancer, we compared radiation responses in two types of non‐small cell lung cancer (NSCLC) cells with different radiosensitivity. In radioresistant NSCLC cells, ionizing radiation (IR) led to CK2α‐ and PKC‐mediated phosphorylation of rpS3 and TRAF2, respectively, which induced dissociation of rpS3‐TRAF2 complex and NF‐кB activation, resulting in up‐regulation of prosurvival genes. Also, dissociated phospho‐rpS3 translocated into nucleus and bound with NF‐кB complex, contributing to p65 DNA binding property and specificity. However, in radiosensitive NSCLC cells, IR‐mediated rpS3 phosphorylation was not detected due to the absence of CK2α overexpression. Taken together, our findings revealed a novel radioresistance mechanism through functional orchestration of rpS3, TRAF2, and NF‐кB in NSCLC cells. Moreover, we provided the first evidence for the function of rpS3 as a new TRAF2‐binding protein and demonstrated that phosphorylation of both rpS3 and TRAF2 is a key control point of radioresistance in NSCLC cells.Grant Funding Source: Supported by the Radiation Technology R&D Program (2013M2A2A7042502)
Regulation of actin dynamics during Legionella pneumophila infection: a novel function of Naip5 (611.2)
Authors: Caution Kyle , Akhter Anwari , Hassan Hoda , Tazi Mia , Voss Oliver , Doseff Andrea , Amer Amal 
Published: June 2021

Clearance of Legionella pneumophila (Legionella), the causative agent of Legionnaire’s disease, a potentially fatal pneumonia, requires efficient phagolysosomal fusion. Regulation of the host actin cytoskeleton is crucial for proper vesicle trafficking, which in turn promotes efficient phagosome‐lysosome fusion and destruction of invading pathogens. Naip5 is an intracellular NOD‐like receptor (NLR) that detects and promotes the degradation of Legionella via its flagellin. The molecular mechanisms of Naip5‐mediated clearance are unknown. It is this study’s objective to decipher the effect of Naip5 on actin dynamics and its upstream regulators to promote phagosome‐lysosome fusion and restriction of the bacterium.During Legionella infection, Naip5‐/‐ bone marrow‐derived macrophages (BMDMs) exhibited less phagosome‐lysosome fusion events, which was due to lack of caspase‐7 activation. The absence of active caspase‐7 in Naip5 cells inhibited the dephosphorylation (activation) of cofilin, blocking formation of new actin filaments. This lack of F‐actin formation hinders efficient phagolysosomal fusion and therefore allows intracellular replication of Legionella.Taken together, these data establish for the first time that Naip5 regulates actin polymerization during infection with Legionella by activating caspase‐7 to modulate the activation of the upstream regulator of actin: cofilin. Understanding the novel molecular mechanisms of Naip5 regulation of the host cytoskeletal network will provide novel targets to develop therapeutic interventions for numerous infectious diseases.Grant Funding Source: Supported by: R01HL094586
A roadmap for GPCR trafficking pathways (613.8)
Authors: Bahouth Suleiman , Nooh Mohammed 
Published: June 2021

The ß1‐adrenergic receptor (ß1‐AR) is a target for treatment of major cardiovascular diseases such as heart failure and hypertension, but the mechanisms of its trafficking are obscure. Recycling of agonist‐internalized ß1‐AR is dependent on two domains the PDZ in the C‐tail and Ser312 in the third intracellular loop. Cross‐talk between a complex composed of SAP97‐AKAP79/PKA that is tethered to the PDZ promoted the phosphorylation Ser312, which served as the recycling signal for this GPCR. Site‐directed mutagenesis of the ß1‐AR PDZ indicated that ß1‐AR recycling was inhibited by mutations in the PDZ that interfered with SAP97 binding and by the inhibition of PKA. The trafficking effects of short sequences differing in their PDZ architecture indicated that PDZs, which bound SAP97, facilitated the recycling of the ß1‐AR in a PKA‐sensitive manner. ß1‐AR chimera containing non‐PDZs derived from recycling other proteins, promoted rapid recycling of chimeric ß1‐AR in SAP97‐ and PKA‐independent manner. These data indicated that a roadmap for the trafficking of this GPCR could be constructed that involves three branches, one for ß1‐AR chimera that recycle in a “sequence‐dependent” manner, another for ß1‐AR chimera that recycle in a “sequence independent” manner and a third for “non‐recycling” ß1‐AR chimera. We will also show that inter conversion between these three trafficking highways is possible by subtle mutations in the ß1‐AR structure or milieu.Supported by NIH, HL‐085848.Grant Funding Source: Supported by NIH, HL‐085848
5‐Fluoro‐2‐[4‐[(2‐phenyl‐1H‐imidazol‐5‐yl)methyl]‐1 piperazinyl]pyrimidine is a mechanism based inactivator of CYP3A4 (615.6)
Authors: Bolles Amanda , Nomeir Amin , Furge Laura 
Published: June 2021

Human cytochrome P450 3A4 (CYP3A4) is responsible for the metabolism of over fifty percent of pharmaceutical drugs on the market today. Inhibition of CYP3A4 can lead to adverse drug‐drug interactions. 5‐Fluoro‐2‐[4‐[(2‐phenyl‐1H‐imidazol‐5‐yl)methyl]‐1‐piperazinyl]pyrimidine (SCH66712) has been previously identified as a mechanism based inactivator (MBI) of CYP2D6 and preliminarily data also suggested it could be an inactivator of CYP3A4 [Palamanda, Casciano, Norton, Clement, Favreau, Lin, Nomeir (2001) Drug Metab Dispos 29, 863‐867]. In the current study SCH66712 was shown to be an MBI of CYP3A4. Inhibition of CYP3A4 by SCH66712 was determined to be concentration‐, time‐ and NADPH‐dependent. In addition, inactivation of CYP3A4 by SCH66712 was shown to be unaffected by the presence of electrophile scavengers. SCH66712 displays type II binding to CYP3A4 with a spectral binding constant (Ks) of 43 ± 2 μM. The partition ratio was determined to be 11, suggesting SCH66712 is a potent MBI of CYP3A4. Analysis of possible mechanism of inactivation are also described.Grant Funding Source: Supported by NIH 1R15‐GM086767‐02
Systematic approach to the assessment of suicidal behavior (618.22)
Authors: Danbayev Serik , Tell Damilya 
Published: June 2021

The research and modern literature data suggest the organizational structure of behavioral suicidal act. The impact of stress factors in the external and internal environment causes a negative psycho‐emotional reaction.The severity of this reaction will depend largely on the state of stress‐limiting systems. In turn, psycho‐emotional response will depend on a number of related factors: genetic, previously carried diseases, disorders, psycho‐social environment; disorders of neuro‐vegetative regulation peculiarities and mental reactions, hormonal status (cortisol, prolactin, thyroid hormones and bioactive connections, etc.), availability of previous alcoholism or drug addiction; metabolic features of the body and brain, in particular, the level of cholesterol in the blood, disorders of the immune system, etc. An important element in the formation of functional and pathological disorders of the central nervous system is a hormonal link. Our data indicate that more than 58% of suicide population (girls) holds inconsistency adaptive and compensatory mechanisms, expressed in varying degrees. Girls with more severe rehabilitation period, but with a stable hyperprolactinemia have significant increase in cortisol levels (2.22 times) is accompanied by a relatively less pronounced increase in prolactin levels (1.8 times), resulting in a low rate of BPD/K. This may indicate that persistent hyperprolactinemia against kortizolemia can be one of the factors that shape disrupting the mechanism of adaptation, in particular the failure of its stress‐limiting link. Conditions of formation of suicidal activity have been originated from these factors. At their worst combination is a qualitatively new emotional state with an orientation to suicide. Study of the functional constituents of the system and the determination of their role in the system will effectively act on these components and prevent suicide attempts.
Brain imaging of nutrition related cognitive development in rural Gambia: studies from birth to 24 months of age (619.1)
Authors: Halliday Drew , Lloyd‐Fox Sarah , Begus Katarina , Maris Helen , Papademetriou Maria , Everdell Nick , Darboe Momodou , Prentice Andrew , Moore Sophie , Elwell Clare 
Published: June 2021

Appropriate nutrition in the first 1000 days of life is essential for optimal brain development and function. Neurobehavioral assessments of cognitive function can only be used to detect effects of nutritional deficiencies once they reach the point of observable behaviour, thus reducing the possibility of targeted early intervention strategies. The aim of this study was to demonstrate the use of optical imaging as an assessment tool for cognitive function in the first two years of life for nutrition based studies in a resource poor setting.Near infrared spectroscopy (NIRS) is an optical imaging technique which measures the haemodynamic response to neuronal activation. A typical system comprises pairs of optical sources and detectors placed over the scalp using a lightweight headband. Each source‐detector pair provides a measure of regional changes in haemodynamics from which an image of localised brain function can be reconstructed. NIRS is completely non invasive, systems are portable, easy to setup and run, protocols are tolerant of participant motion, and non experts can easily be trained to perform the studies. We transported an NIRS system to a field station in rural Gambia to study infants from three age groups (4‐8 month‐olds n = 24; 9‐13 month olds n = 26; 18‐24 month‐olds, n = 20). NIRS was used to measure brain activation to visual and auditory social and non social stimuli. Significant activation was seen during auditory social (e.g., laughter) compared to auditory non social (e.g., toy rattles) conditions ‐ as well as to visual social (human peek‐a‐boo) compared to visual non social (transport images) ‐ in channels localised over the right posterior temporal hemisphere. These results confirm the viability of optical neuroimaging techniques to assess cognitive function in resource poor settings, and suggest that vocal selectivity can be used to differentiate neurodevelopmental trends in visual and auditory processing during the critical first 1000 days of life.Grant Funding Source: Bill and Melinda Gates Foundation
Effects of prenatal micronutrient supplementation on school age child behavior (619.6)
Authors: Bahnfleth Charlotte , Murray‐Kolb Laura , Schaefer Barbara , Cole Pamela , Khatry Subarna , LeClerq Steven , Christian Parul 
Published: June 2021

The long‐term behavioral effects of prenatal micronutrient supplementation have yet to be explored thoroughly. We examined behavior in 7‐9 year old Nepali children (n=676) whose mothers received prenatal micronutrient supplementation as part of a double‐masked RCT. Also, since we previously reported that supplementation with iron‐folic acid (cIFA) during the preschool years resulted in higher demandingness at 7‐9 years, further analyses were conducted to determine if prenatal IFA conferred an added benefit to cIFA (n=334). Mothers were randomized to daily multiple micronutrient (MM); iron‐folic acid (IFA); IFA + zinc (IFAZn); placebo (PL). Child behavior was assessed on six dimensions (positive mood; negative mood; lively/active; sociability; sustained attention; demandingness) during two home observation periods. Differences in behavior ratings were examined relative to the PL for each supplementation group. In both unadjusted and adjusted analyses, children whose mothers had received IFA were more likely to have higher ratings of demandingness (p<0.05 for both) while they were more likely to have lower ratings of lively/activity (p<0.05 for both) compared to the PL group. IFAZn or MM did not have any effect on child behavior. In both unadjusted and adjusted analyses, those who received both prenatal IFA and cIFA were more likely to have higher ratings of sociability (p<0.05 for both) than those who had only received cIFA. Prenatal supplementation with IFA appears to impact child behavior in the long‐term.Grant Funding Source: Supported by NICHD and Gates Foundation
Intrauterine growth influences growth and body composition of Peruvian children (620.3)
Authors: Mispireta Monica , Zavaleta Nelly , Merialdi Mario , DiPietro Janet , Putnick Diane , Bornstein Marc , Caulfield Laura 
Published: June 2021

Our objective was to test whether intrauterine growth in the second half of pregnancy is associated with anthropometric and body composition measures in early childhood. We used data from a prenatal zinc supplementation trial in Peru (n=177) to estimate fetal growth using serial ultrasound measures of head circumference, abdominal circumference, femur diaphysis length, and estimated fetal weight (20‐38 wk gestation), and measures of growth and body composition (weight, height, body mass index (BMI), waist circumference, sum of skinfolds, and fat and muscle areas of extremities) evaluated at a follow‐up visit at 4.5 y. We constructed separate linear regression models for each fetal size measure in mid‐gestation (20‐24 wk), end of pregnancy (36‐38 wk), and the net difference between them and each measure of growth and body composition in childhood. In models adjusted for child and maternal factors, measures of fetal size at end of pregnancy and the difference in fetal size between mid‐gestation and end of pregnancy were positively associated with measures of growth, adiposity, and lean body mass at 4.5y. None of the fetal size measures in mid‐pregnancy were associated with child size or body composition. These results suggest that the fetal growth during the final few weeks of pregnancy influences size and body composition in early childhood.Grant Funding Source: Supported by Nestle Research Foundation; HD042675; NICHD; American Heart Association
Stunting is characterized by chronic inflammation in Zimbabwean infants (620.4)
Authors: Prendergast Andrew , Rukobo Sandro , Chasekwa Bernard , Mutasa Kuda , Ntozini Robert , Mbuya Mduduzi , Jones Andrew , Moulton Lawrence , Stoltzfus Rebecca , Humphrey Jean 
Published: June 2021

Background Stunting affects one‐third of children in developing countries, but the causes remain unclear. The objective of this study was to investigate whether low‐grade inflammation suppresses the growth hormone‐IGF axis and mediates stunting.Methods We conducted a case‐control study of 202 HIV‐unexposed Zimbabwean infants who were stunted (height‐for‐age Z‐score (HAZ)<‐2; cases) or non‐stunted (HAZ>‐0.5; controls) at 18mo. We measured biomarkers of intestinal damage (I‐FABP), inflammation (CRP, AGP, IL‐6) and growth hormone‐IGF axis (IGF‐1, IGFBP3) in infant plasma at 6w and 3, 6, 12 and 18mo, and in paired maternal‐infant plasma at birth. Adjusted mean differences between biomarkers were estimated using regression models. Multivariate odds ratios of stunting were estimated by logistic regression.Results At birth, cases were shorter than controls and their mothers had lower levels of IGF‐1 (adjusted mean difference(95%CI) ‐21.4(‐39.8, ‐3.1) ng/mL). From 6w‐12mo of age, levels of CRP and AGP were consistently higher and IGF‐1 and IGFBP3 lower in cases versus controls; IGF‐1 correlated inversely with inflammatory markers at all time‐points. I‐FABP increased between 3‐12mo, indicating extensive intestinal damage, which was similar in cases and controls. In multivariate analysis, higher levels of CRP (aOR 3.06 (95%CI 1.34, 6.99); P=0.008) and AGP (aOR 7.87 (95%CI 0.74, 83.74); P=0.087) during infancy were associated with stunting.Conclusions Stunting began in utero and was associated with low maternal IGF‐1 at birth. Inflammatory markers were higher in cases than controls from 6w of age and were associated with lower levels of IGF‐1 throughout infancy. Higher levels of CRP and AGP during infancy were associated with stunting. These findings suggest that an extensive enteropathy occurs during infancy and that low‐grade chronic inflammation may impair infant growth.Grant Funding Source: Supported by Wellcome Trust (UK)