bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tapping the Power of Plasma Lipidome to Improve Hypertriglyceridemic Waist as a Predictor of Future Type 2 Diabetes
Authors: Mamtani Manju , Meikle Peter , Kulkarni Hemant , Wong Gerard , Weir Jacquelyn , Barlow Christopher , Dyer Thomas , Almasy Laura , Mahaney Michael , Comuzzie Anthony , Duggirala Ravindranath , Blangero John , Curran Joanne 
Published: June 2021

Hypertriglyceridemic waist is considered a specific predictor of T2D because it combines the predictive value of waist circumference (WC) and serum triglycerides (TG). Our objective was to investigate if the addition of specific triacylglycerol (TAG) lipid species to WC performs better than the combination of WC and TG to predict future T2D in initially diabetes‐free individuals (n=771, 9197 person‐years follow‐up). The participants were from the San Antonio Family Heart Study and the plasma lipidome was quantified using high‐performance liquid chromatography and mass spectrometry. A forward addition approach to optimize the integrated discrimination index (IDI) identified five independent and significant TAG species out of 43 species investigated.

Selection of TAG species using stepwise forward added IDI
Association of TAG species with T2D

Step
TAG Retained
IDI
p
Scale
Coefficient
p

1
TAG 16:0/16:0/18:2
0.0278
0.0031
10‐4
0.6915
0.0004

2
TAG 14:1/18:1/18:1
0.0264
8.9x10‐5
10‐3
‐0.4125
0.0003

3
TAG 18:0/18:2/18:2
0.0025
0.0391
10‐3
‐0.2426
0.0278

4
TAG 16:0/18:1/18:1
0.0075
0.0224
10‐5
1.1917
0.0105

5
TAG 14:0/18:2/18:2
0.0070
0.0209
10‐3
0.5095
0.0308

A summary TAG score was constructed from these five TAG species based on logistic regression model as shown in Table 1. Comparison of the predictive performance of the TAG score with that of TG concentration demonstrated the additive value of the TAG score but not of TG to basic clinical predictors of T2D including prediabetes.

Statistic
Base Model Estimate (p)
Base Model + Prediabetes Estimate (p)

ΔAROC TAG Score
0.0374 (0.0063)
0.0274 (0.0014)

IDI TAG Score
0.0726 (5.3x10‐7)
0.0585 (9.9x10‐6)

NRI TAG Score
0.6008 (5.7x10‐10)
0.5937 (8.9x10‐10)

ΔAROC TG
0.0035 (0.4472)
0.0014 (0.6156)

IDI TG
0.0059 (0.0407)
0.0011 (0.2827)

NRI TG
0.3500 (0.0002)
0.1553 (0.0578)

Our results provide two interesting implications: first, not all TAG species are similar (either in strength or direction of association) with regards their predictive value for future T2D; and second, few TAG species from the plasma lipidome can be combined with WC to significantly improve the prediction of future T2D.This work was supported in part by NIH grants, AT&T Foundation anad facilities supported by NIH grants.
Inositol Depletion Perturbs the Vacuolar‐ATPase: A Novel Mechanism of Action of Valproate
Authors: Deranieh Rania , Shi Yihui , Tarsio Mauraeen , Kane Patricia , Greenberg Miriam 
Published: June 2021

Depletion of inositol has profound effects on cell function and has been implicated in the therapeutic effects of drugs used to treat bipolar disorder. We have previously shown that one such drug, valproate (VPA), depletes inositol by inhibiting myo‐inositol 3‐phosphate synthase, the enzyme that catalyzes the first and rate‐limiting step of inositol biosynthesis. To elucidate the cellular consequences of inositol depletion, we screened the yeast deletion collection for VPA‐sensitive mutants and identified mutants in vacuolar sorting and the V‐ATPase.Inositol depletion caused by VPA or by starvation of ino1Δ cells perturbed the vacuolar structure, decreased V‐ATPase activity and proton pumping in isolated vacuolar vesicles. VPA compromised the levels of PI3,5P2, which is necessary for stabilization of the V‐ATPase complex, and resulted in reduced V‐ATPase activity. Osmotic stress, known to increase PI3,5P2 levels, did not restore the compromised PI3,5P2 levels, nor did it induce vacuolar fragmentation in VPA‐treated cells, suggesting that perturbation of the V‐ATPase is a consequence of altered PI3,5P2 homeostasis under inositol‐limiting conditions. The findings of this study are the first to demonstrate that inositol depletion caused by starvation of an inositol synthesis mutant or by the inositol‐depleting drug VPA leads to perturbation of the V‐ATPase.
RNA‐Seq Reveals Differential hnRNP‐RNA Interactions During VSV Infection
Authors: Davidson Adam , Lyles Douglas , Alexander Rebecca 
Published: June 2021

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a class of RNA‐binding proteins that carry out numerous cellular functions. hnRNPs serve as RNA shuttling proteins in healthy cells, transporting nascent RNA from the nucleus to the cytoplasm. Recent work by others has shown that hnRNP A1, hnRNP K and hnRNP C1/C2, among others, are relocalized to the cytoplasm during infection by vesicular stomatitis virus (VSV), the purpose of which is not fully understood.Vesicular Stomatitis Virus (VSV) is a non‐segmented negative strand virus of the Rhabdoviridae family. Genomic VSV is transcribed by virally encoded RNA‐dependent RNA polymerase to generate the mRNA responsible for protein synthesis in the host cell. As a weak human pathogen, it is a model organism for the more infectious viral agents influenza and rabies. VSV is an emerging player in oncolytic viriotherapy, as it is capable of tumor suppression through a variety of mechanisms including cellular hypoxia, inflammatory cytokine release and direct cell lysis.In the context of innate immunity, the interaction between hnRNPs and both viral and cellular mRNA is explored through RNA‐Seq, a deep‐sequencing approach. Each hnRNP displays a differential affinity for cellular and viral transcripts between mock‐infected and VSV‐infected states, indicating the occurrence of RNA exchange and a directed purpose for this host‐pathogen interaction.
Altering Caspase Specificity Using an Intracellular Directed Evolution Approach
Authors: MacPherson Derek , Hill Maureen , Wu Peng , Hardy Jeanne 
Published: June 2021

Caspases are among the most specific of proteases, making them ideal targets for engineering new specificity and developing new protease‐based biotherapeutics. However, conventional high‐throughput methods for protein evolution are not amenable to caspases as they are multi‐chain, and intracellular. Increasing the complexity, active sites of caspases are highly flexible to allow for accommodation of various substrates, making a rational design approach difficult To overcome these challenges, we developed a method for evolving function in cytosolic proteases, based on our novel genetically‐encoded caspase activatable‐GFP reporter (CA‐GFP), which is activated from a dark to a fluorescent state by proteolysis.Our first application of this technology, we engineered caspase‐7, which cleaves the amino acid sequence DEVD to recognize and cleave the new sequence VEID, recognized by caspase‐6. Saturation mutagenesis at key residues within the active site of the enzyme allowed us to sort for variants with altered specificity by flow cytometry. Variants able to cleave the target sequence were purified, then characterized using traditional Michaelis‐Menten kinetics, protein substrate assays and x‐ray crystallography. We identified several variants that displayed kinetic activity and cleavage patterns similar to the wild type caspase‐6. X‐ray crystal structures of the evolved variants bound to the casp‐6 and ‐7 cognate substrates VEID, and DEVD reveal how the mutations affect the activity of the enzyme, which could not be rationally predicted, emphasizing the strength of this approach. Utilizing this method we are able to reengineer cytosolic proteases to cleave novel targets and pave the way for biotherapeutic applications.This work is supported in part by NIH GM080532.
Pharmacological Properties of Anthocleista vogelii against CCl4 Induced Toxicity
Authors: IROANYA ONYEKACHI , ODUOLA TAIWO , AKAGHA MILDRED , OLADUNJOYE ENITAN 
Published: June 2021

The Hematopoietic, Hepatoprotective Lipid Peroxidative, Enzymic & Non Enzymic properties of 70% aqueous EtOH extract of Anthocleista vogelii leaves (AEEAV) was ascertained using Wistar albino rats.The animals (30) were divided into 6 groups. Groups 1 & 2 received distilled water (10 ml/kg p.o.) for 7 days & served as normal & toxin controls respectively. Groups 3, 4 & 5 were treated with 200, 400 & 800 mg/kg of AEEAV (p.o.) respectively while Group 6 received Silymarin (300 mg/kg p.o.) for 7 days. On the 7th day, group 1 recieved 1 ml/kg of liquid paraffin (i.p.) while Groups 2, 3, 4, 5 & 6 received 1 ml/kg of 50 % (v/v) CCl4 in liquid paraffin (i.p.) 6 hrs after the last dose. After 24 hrs the animals were sacrificed.In serum liver and kidney, AEEAV dose dependently showed significant (p<0.05) increase in Catalase Glutathione Peroxidase Superoxide Dismutase Reduced Glutathione & Glutathione S Transferase levels with decrease in the level of MDA compared to the normal & toxin control groups. On administration of 800 mg/kg of AEEAV, ALP, AST and ALT levels were significantly low (p<0.05) compared to 200 & 400 mg/kg but almost the same as silymarin. AEEAV showed significant (p<0.05) increase in Albumin and Total Protein levels but decreased the concentrations of Triglyceride Cholesterol Urea Bilirubin &Creatinine compared to toxin control group. There was significant (p<0.05) increase in PCV, Hb, platelet & MCH levels compared to the toxin control group.The toxic effect of CCl4 was significantly attenuated (p<0.05) on treatment with AEEAV by restoring the liver function to near normal indicating the protection of hepatic cells, increasing the rate of erythropoiesis and antioxidant activity.
Inhibition of Neisseria meningitidis Group X N‐Acetylglucosamine‐1‐Phosphotransferase by Donor Substrate Analogues
Authors: Cottman‐Thomas Ebony , Ming Shonoi , Tedaldi Lauren , Wagner Gerd , Chen Yi , Chen Xi , Cai Cao , Linhardt Robert , Vann Willie 
Published: June 2021

Neisseria meningitidis is a major cause of bacterial meningitis in the meningitis belt of Sub‐Saharan Africa. N. meningitidis serogroup X is increasing prevalence in the meningitis belt. The capsular polysaccharide is a homopolymer of (α1‐4)‐linked N‐acetyl‐D‐glucosamine (GlcNAc)‐1‐phosphate. We have shown that the enzyme responsible for formation of this polymer is a GlcNAc‐1‐phosphotransferase that catalyzes the transfer of a GlcNAc‐1‐phosphate from UDP‐GlcNAc to the 4‐hydroxyl of a terminal GlcNAc‐1‐phosphate on the growing polysaccharide chain.In this investigation we explore its interaction with substrates analogs of the sugar nucleotide donor, UDP‐GlcNAc. Recently a sugar nucleotide inhibitor was described for glycosyltransferases based on a proposed conformation change induced by donor binding. We demonstrated that several of these novel analogs of UDP‐GlcNAc are indeed inhibitors. The best inhibitors contained a bulky thien‐2‐yl group at the 5‐positon of uracil.UDP‐GalNAc, which differs from the UDP‐GlcNAc only by the orientation of the sugar 4‐hydroxyl group, and UDP‐Glc, which differs by the absence of an acetamido group were neither substrates nor inhibitors suggesting that the 4‐hydroxyl and the 2‐acetamido may be important for interaction of the sugar moiety. Both UDP‐trifluoroacetylglucosamine and UDP‐azidoacetylglucosamine were good inhibitors of GlcNAc‐1‐phosphoryltransferase, confirming the importance of the acetamido group.
The Effect of a Sulforaphane and Maitake Mushroom Extract Combination on the Expression of NAD(P)H:Quinone Oxidoreductase 1 (NQO1) and Glutathione S‐Transferase theta‐1 (GSTT1)
Authors: Erwin Sharis , Ownby Stacy , Slider Laxmi , Cornblatt Grace 
Published: June 2021

Humans are exposed to numerous environmental threats on a daily basis. Our bodies are able to naturally eliminate these toxins in a series of reactions catalyzed by Phase 1 and Phase 2 enzymes, which occur primarily in the liver. Phase 1 enzymes convert toxins into reactive intermediates which can diffuse through cell membranes and negatively interact with DNA, proteins, or lipids. These reactive intermediates are further modified by Phase 2 enzymes which solubilize the reactive intermediates allowing for excretion from the body. Here we examine a novel blend of sulforaphane and maitake mushroom extract and their effect on the detoxifying enzymes. Previously, our laboratory has shown that the combination of sulforaphane and maitake mushroom extract can induce such detoxifying enzymes as UDP glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1). In this study, we focus on the effect of the combination of sulforaphane and maitake mushroom extract on Phase 2 enzymes in cultured liver cells over a series of time points using qRT‐PCR, Western blot analysis, and immunofluorescence. Elevated levels of NQO1 and GSTT1 were observed over a course of 72 hours. This demonstrates that the combination of sulforaphane and maitake mushroom extract can induce the production of the phase 2 enzymes needed to promote clearance of potentially reactive intermediates.Funding: Nutramax Laboratories, Consumer Care, Inc.
Phosphonylated Acetylcholinesterase: Probing the Mechanism of a Small Molecule Reactivator
Authors: Cadieux C Linn , Wang Haoyu , Zhang Yuchen , Koenig Jeffrey , Shih Tsung‐Ming , McDonough John , Koh John , Cerasoli Douglas 
Published: June 2021

Currently fielded treatments for nerve agent intoxication include atropine, an acetylcholine receptor antagonist, and pralidoxime (2PAM), a small molecule reactivator of acetylcholinesterase (AChE). 2PAM reactivates nerve agent‐inhibited (NA‐)AChE via direct nucleophilic attack by the oxime moiety on the phosphorus center of the bound nerve agent. Due to a permanently charged pyridinium motif, 2PAM is not thought to cross the blood brain barrier and therefore cannot act directly in the neuronal junctions of the brain. In this study, a non‐permanently charged, non‐oxime molecule initially identified using pesticide‐inhibited AChE was tested for reactivation potential against NA‐AChE. The inhibitory and reactivation potentials of the molecule were determined with native AChE and AChE inhibited with tabun, sarin, soman, cyclosarin, VX, or VR and then compared to those of 2PAM. Then, several structural analogues of the candidate were used to probe the reactivation mechanism of the molecule. Additionally, the experimental condition under which reactivation was performed was altered in an attempt to determine the active form of the molecule. Finally, guinea pigs were used to examine the protective efficacy of the compound after exposure to sarin. Together, the results of both in vitro and in vivo testing will inform the design of future NA‐AChE small molecule reactivators. This research was supported by the Defense Threat Reduction Agency ‐Joint Science Technology Office, Medical S&T Division.
Unsaturated Fatty Acids Stimulate Tumor Growth through Stabilization of β‐Catenin
Authors: Kim Hyeonwoo , Rodriguez‐Navas Carlos , Kollipara Rahul , Kapur Payal , McDonald Jeff , Brugarolas James , Kittler Ralf , Ye Jin 
Published: June 2021

Cancer cells alter their metabolism to adapt for their uncontrolled proliferation. One of such alterations leads to accumulation of free fatty acids (FAs), which facilitate proliferation of some cancer cells through a mechanism yet to be identified. Here we report that excess unsaturated FAs block degradation of β‐catenin, the aberrant accumulation of which triggers development of various cancers. Interestingly, unsaturated FAs stabilize β‐catenin through a mechanism independent from that mediated by Wnt, a protein known to block degradation of β‐catenin. Unlike Wnt, unsaturated FAs do not affect ubiquitination of β‐catenin. Instead, the lipids block degradation of ubiquitinated β‐catenin through Fas‐associated factor 1 (FAF1), a protein known to facilitate degradation of β‐catenin through its interaction with the protein. We now show that FAF1 directly binds to unsaturated FAs. This interaction triggers polymerization of FAF1, causing dissociation of the protein from β‐catenin and consequently stabilization of β‐catenin. This finding is clinically relevant, as excess unsaturated FAs accumulated in clear cell renal cell carcinoma promote growth of the tumor through stabilization of β‐catenin. Our study indicates that overaccumulation of unsaturated FAs is a novel mechanism for cancer cells to acquire excess β‐catenin.This study is supported by grants from NIH (HL‐20948), Welch foundation (I‐1832), and Clayton Foundation for Research.
Burn‐injury Alters Brain Catecholamine Levels and β‐AR Signaling
Authors: El Ayadi Amina , Wang Ye , Guillory Ashley , Herndon David , Finnerty Celeste 
Published: June 2021

The prefrontal cortex is the most evolved brain region sensitive to the detrimental effects of stress exposure. Burn injury causes a dramatic increase in systemic catecholamines (CAs) levels accompanied by a post‐burn hypermetabolic response and chronic activation of beta adrenergic (β‐AR)‐mediated signaling. While many have addressed the systemic effects of burn‐ induced CAs, to our knowledge, no one has looked at the central effects of burn‐induced stress. In this study we are analyzing the effect of burn injury on CAs levels and β‐AR signaling in the prefrontal cortex.To this end, we used our rat burn scald model with a 60% total body surface area scald burn. Rats were burned according to established published procedures. The animals were sacrificed at 2,6, 24 hours and 1 week post‐burn. The brain immediately removed, dissected and stored at ‐80.We used 3‐CAT ELISA kit to determine CAs levels, catch point assay to determine cAMP levels, and PKA activity was measured using a kit. Western blot analysis was used to analyze the β‐AR expression and downstream signaling targets.We found that burn injury increases adrenaline levels at 2 and 6 hrs post‐burn while significantly decreasing noradrenaline levels at the same time points. PKA levels were significantly increased 7 days post‐burn. Levels of cAMP were not significant different. We analyzed the role of the β‐AR signaling following burn injury and found that β2‐AR levels were significantly increased 7 days. PKA levels were increased at 6hrs (P<0.001). The Gs levels were decreased at 6 hrs while the levels of Gi protein were initially decreased before increasing at 1 week post‐burn.These data show that burn injury alters brain CAs and subsequent β‐AR signaling activation possibly via both the canonical and the non‐canonical pathways.
Calpain‐1 Knockout in Mice Causes Degeneration of Cerebellar Granule Cells and Ataxia
Authors: Lopez Dulce , Pinto Vanessa , Wang Yubin , Liu Yan , Seinfeld Jeffrey , Bi Xiaoning , Baudry Michel 
Published: June 2021

Abnormal apoptosis is one of the hallmarks of human neurodegenerative disorders, such as spinocerebellar ataxia (SCA), an inherited disease with progressive deterioration of gait and balance, associated with neuronal loss in cerebellum. A recent study reported that SCA in the Parson Russell Terrier dog breed was associated with a calpain‐1 null mutation. Contrary to the established view that overactivation of calpains, a family of calcium‐dependent proteases, leads to neurodegeneration, recent results have shown that synaptic N‐methyl‐D‐aspartate receptor (NMDAR)‐mediated calpain‐1 activation produces neuroprotection via degradation of PH domain and Leucine rich repeat protein phosphatase 1 (PHLPP1), and stimulation of the pro‐survival Protein Kinase B (Akt). Here, we report that the number of apoptotic neurons in various brain structures, including cerebellum, is higher in calpain‐1 knock out (CAPN1 KO) mice, as compared to wild‐type (wt) mice during the postnatal period (P7‐P10). Adult CAPN1 KO mice exhibited reduced granule cell density and impaired motor function. PHLPP1 was increased and p‐Akt decreased in cerebellum of CAPN1 KO mice, as compared to wt mice during postnatal development. Systemic injection (P1‐P7) of Bisperoxo Oxovanadate Dipotassium (BPV), an indirect activator of Akt, as well as crossing CAPN1 KO mice with PHLPP1 KO mice, rescued Akt activation, reduced apoptosis in the developing cerebellum, resulting in increased granule cell survival and improvement of motor function in adult mice. These findings further support the notion that CAPN1 is neuroprotective and suggests that it is a new candidate gene for ataxia.Funded by NINDS grant P0INS045260‐01.
Organic and Conventional Strawberry: Nutritional, Physical‐chemical, Antioxidant, and Pesticide Residues Composition.
Authors: Costa Neuza , Kobi Helia , Silva Pollyanna , Souza Jacimar 
Published: June 2021

Conventional agriculture, based on the use of chemical, mechanical and biological inputs, can affect the environment and human health and, in view of this, sustainable models of organic production have been proposed. The objective of this study was to compare the nutritional, physical‐chemical and antioxidant properties and pesticide residues of strawberries grown under organic or conventional systems. Strawberries (Fragaria x ananassa Duchesne) cultivar Camarosa were produced in conventional or organic systems, under controlled agricultural conditions. Their compositions were analyzed regarding moisture, protein, carbohydrate, lipids, ash, pH, soluble solids, total solids, total titratable acidity, vitamin C, anthocyanin, total phenolic compounds, antioxidant capacity and pesticide residues (azoxystrobin, lambda‐cyhalothrin and thiamethoxam).The organic strawberries showed higher moisture (91.48 vs 91.03 mg/100g) and ash (0.43 vs 0.35 mg/100g) contents, while conventional strawberries had higher total solids (8.98 vs 8.53%), soluble solids (8.50 vs 8.13 °Brix), Protein (0.93 vs 0.75 mg/100g) and carbohydrate (6.80 vs 6.44 mg/100g). The pesticide residues in organic strawberry were below the limit of detection (<LOD) and the values in the conventional strawberries were below the limit of quantification (<LOQ). Under controlled crop production, the cultivation system did not affect substantially the nutritional, physical‐chemical and antioxidant properties and pesticide residues of strawberry.Acknowledgement: FAPES for financial support.
Short Pictorial Vegetable Behavioral Scale Demonstrates Convergent Validity with MyPlate Cup Equivalents of Vegetables
Authors: Townsend Marilyn , Shilts Mical , Styne Dennis , Drake Christiana , Aden Christopher , Ontai Lenna 
Published: June 2021

Valid evaluation tools are needed, particularly for low‐literate participants of federal food assistance and education programs. Our objective is to provide evidence of convergent validity for a 9‐item pictorial vegetable behavioral assessment for use by these federal programs. Parents (n=144) from Head Start and Supplemental Food for Women, Infants and Children [WIC] provided parent self‐administered Healthy Kids (HK) and three child 24‐hour diet recalls. The 9‐scale [recoded to the healthy direction] produced an alpha of .83. This scale was positively related to a sum of the volume of vegetables in cup equivalents for dinner from the food logs. Linear regression identified the strongest predictor items using cup equivalents as the outcome [r=.54, p<.00001]. Spearman correlations produced significant unweighted results [r=.40, p<.0001]. The scale was significantly related to hypothesized nutrients: folate, Vitamin C, soluble fiber, beta‐carotene. The resulting short pictorial assessment with low‐respondent burden may be useful in evaluating vegetable behaviors among low‐literate program participants.Supported by National Research Initiative (NRI) #2009‐55215‐05019 & Agriculture and food Research Initiative (AFRI) #2010‐85215‐20658 from the USDA National Institute of Food and Agriculture (NIFA), Human Nutrition and Obesity 93330.