bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of immunodeficiency on motoneuron survival and peripheral nerve regeneration following facial nerve axotomy
Authors: Beahrs Taylor R , Sanders Virginia M , Jones Kathryn J 
Published: June 2021

Facial nerve axotomy is a well‐described injury model for peripheral nerve regeneration and facial motoneuron (FMN) survival. After facial nerve transection, FMN survival levels in Rag2 KO mice (lacking functional T and B cells) are ~60% compared to ~86% in wild‐type (WT) mice at 4 week postoperative (wpo). This decrease in Rag2 KO FMN survival can be rescued to WT levels by reconstitution with CD4+T, but not CD8+ or B cells, prior to nerve transection. However, the ability of CD4+T cells to support FMN survival appears to be transient because WT FMN survival levels begin to decrease by 10 wpo, approaching Rag2 KO levels. The first goal of this study is to examine WT FMN survival at extended time points (18 and 26 wpo) to determine whether a functional immune system provides transient neuroprotection, or long‐term support for FMN survival. In addition, we will utilize a crush axotomy to evaluate functional recovery in WT, STAT6 KO (impaired Th2 response), T‐Bet KO (impaired Th1 response), and Rag2 KO mice. Based on the immune‐mediated neuroprotection observed following transection, we speculate that some or all of these immunodeficient mouse models will have impaired functional recovery and/or decreased FMN survival after crush. The specific transgenic models used in this study may also confirm the role of CD4+T cell subsets in immune‐mediated neuroprotection.Supported by NIH grant NS40433 (KJJ & VMS).Grant Funding SourceNIH grant NS40433
The Role of Bicaudal‐C in Kidney Development
Authors: Wessely Oliver , Agrawal Raman , Tran Uyen 
Published: June 2021

The RNA‐binding molecule Bicaudal‐C (BicC1) has been shown to regulate embryonic development in Drosophila and Xenopus. Interestingly, mouse mutants of Bicaudal‐C do not show early developmental defects, but develop polycystic kidney disease (PKD) instead. PKD is among the most common single gene diseases in humans and is the leading cause of end‐stage renal failure. It is characterized by the formation of fluid‐filled cysts in the kidney. Importantly, these cysts are thought to be caused by a defect in cell asymmetry causing kidney epithelial cells to misalign within the tubule leading to an increase of the tubule diameter.Here we provide data that BicC1 functions by regulating the expression of Polycystin‐2 (PC2), a member of the transient receptor potential super family. Knockout of BicC1 in mice results in the formation of early onset PKD characterized by cysts along the entire length of the nephron and reduced expression of PC2 in the kidney. Molecular analyses in Xenopus showed that BicC1 and PC2 cooperate and PC2 is required for the activity of BicC1. Moreover, at the subcellular level BicC1 protein was detected in cytoplasmic foci that were positive for P‐body markers such as GW182. Based on these data we propose that the PKD phenotype caused by loss‐of‐BicC1 in mice is caused by misregulation of of PC2 at the post‐transcriptional level.
Simvastatin Increases Endothelial Nitric Oxide Synthase Expression in Cultured Endothelial Cells Preconditioned with Steady Laminar Flow
Authors: Rossi Joanna , Rouleau Léonie , Tardif Jean‐Claude , Leask Richard L 
Published: June 2021

IntroductionStatins (HMG‐CoA reductase inhibitors) are known to have benefits in vascular biology beyond lipid reduction. It has been reported that statins can elevate the expression of endothelial nitric oxide synthase (eNOS) in cultured endothelial cells; however, it is not known whether this increase is conserved under hemodynamic stimulation. Methods andResultsHuman abdominal aortic endothelial cells were pre‐conditioned with fluid shear stress (1, 10 or 20 dynes/cm2) for 6 h. Without stopping the perfusion, control vehicle, simvastatin or simvastatin with mevalonate were added to the perfusion media and the flow experiment was continued for 24 h. As expected, eNOS mRNA and protein increased with increasing levels of fluid shear stress. Treatment with 1 or 10 µM of simvastatin further elevated eNOS mRNA and protein. Co‐incubation with mevalonate, a precursor to cholesterol synthesis, eliminated the effect of the statin, but had no effect on shear induction of eNOS. This suggests that the effect of statins on eNOS expression is conserved under flow and that the mechanism in which simvastatin induces eNOS is through inhibition of HMG‐CoA reductase.ConclusionsSimvastatin enhances eNOS expression in cultured endothelial cells pre‐conditioned with steady laminar flow through inhibition of HMG‐CoA reductase. These results may explain the benefits of statins in the clinic beyond lipid reduction.
Reduction of the glycemic index by a Novel Viscous Polysaccharide when added or incorporated into commonly consumed foods.
Authors: Jenkins Alexandra , Kacinik Veronica , Lyon Michael , Wolever Thomas , Vuksan Vladimir 
Published: June 2021

Background/ObjectivesReductions of postprandial glucose levels have been demonstrated previously with the addition of a novel viscous polysaccharide (NVP) to a glucose drink and standard white bread. This study explores whether these reductions are sustained when NVP is added to a range of commonly consumed foods.Subjects/MethodsTen healthy subjects (4M, 6F; age 37.3 ± 3.6 y; BMI 23.8 ± 1.3 kg/m²), participated in an acute randomized controlled study. The glycemic response to cornflakes+milk (Cornfl), rice (Rice), yogurt (Yog), a frozen turkey dinner (Turk) with and without 5g of NVP sprinkled on the test meal was determined. In addition, 3 granolas with different levels of NVP , three control white breads, and one white bread and milk were also consumed. Capillary blood samples were taken fasting and at 15, 30, 45, 60, 90 and 120 min after the start of the meal. To quantify the reduction in glycemia the glycemic index (GI) was calculated.ResultsAddition of NVP reduced blood glucose response irrespective of food (p<0.01). The GI of Cornfl, Cornfl+NVP, Rice, Rice+NVP, Yog, Yog+NVP, Turk, Turk+NVP was 83, 58, 82, 45, 55 ,41, 44, and 38 respectively. The GI of the control granola, and granola with 2.5 and 5g of NVP were 64, 33, and 22 respectively.ConclusionSprinkling or incorporation of NVP into a variety of different foods is highly effective in lowering the GI of a food.
Anti‐myeloperoxidase antibodies rapidly induce α4 integrin‐dependent glomerular neutrophil adhesion
Authors: Hickey Michael , Kuligowski Michael , Bourges Dorothee , Lo Cecilia , Kitching A. Richard 
Published: June 2021

Despite the fact that anti‐myeloperoxidase antibodies (anti‐MPO) have been shown to promote leukocyte adhesion in flow‐based assays in vitro and in postcapillary venules in vivo, their role in promoting adhesion in the glomerular vasculature is less clear. We used renal intravital microscopy to examine glomerular leukocyte adhesion induced by anti‐MPO. In mice pretreated with LPS, 50 μg of anti‐MPO induced LFA‐1‐dependent adhesion in glomeruli. In concert with this finding, in mice pretreated with LPS, ~75% of circulating neutrophils bound anti‐MPO within 5 min of intravenous administration. However, even in the absence of LPS pretreatment, ~50% of circulating neutrophils bound anti‐MPO, a response not seen in MPO−/− mice. In addition, a higher dose of anti‐MPO (200 μg) induced robust glomerular leukocyte adhesion in the absence of LPS pretreatment. The latter response was β2‐integrin‐independent, instead requiring the α4‐integrin, which was upregulated on neutrophils in response to anti‐MPO. These data indicate that anti‐MPO antibodies are capable of inducing glomerular leukocyte adhesion via multiple pathways, with lower doses only inducing adhesion in mice receiving an infection‐related stimulus, and higher doses being capable of inducing responses in the absence of an additional inflammatory stimulus, via alternative adhesion mechanisms.Supported by the NHMRC (Australia) & Genzyme
HIV assembly ‐‐ The macrophage scenario
Authors: Marsh Mark , Pelchen‐Matthews Annegret , Theusner Kristina 
Published: June 2021

The assembly of enveloped viruses in eukaryotic cells requires interaction with cellular membrane trafficking and protein sorting machineries. Structural proteins of the virus, and key cellular components, must be brought together in a spatially and temporally controlled manner to allow the formation of infectious virus particles. The human immunodeficiency virus (HIV‐1) is a particularly useful model for analysing these activities. The small genome, and the fact that only three virally encoded proteins are required for infectious particle formation, makes this virus an attractive model for cellular and biochemical analysis.We have studied the formation of HIV in human macrophages and find that particles assemble on the limiting membrane, and bud into the lumen, of an intracellularly sequestered plasma membrane domain. Viruses appear to be stored within this assembly compartment prior to release. This release may be induced when T cells interact with infected macrophages leading to the formation of so‐called (virological synapses) through which viruses are efficiently transferred to T cells. Characterisation of the assembly compartment will likely shed new light on the molecular basis of HIV assembly and provide insights to the ways in which these viruses exploit the properties of monocyte‐derived cells for efficient cell‐to cell transmission.
γ‐GLUTAMYLTRANSFERASE OF CANCER CELLS AT THE CROSSROADS AMONG TUMOR PROGRESSION, DRUG RESISTANCE AND DRUG TARGETING.
Authors: Pompella Alfonso , Corti Alessandro , Zunino Franco , Paolicchi Aldo 
Published: June 2021

γ‐Glutamyltransferase (GGT) is increased human malignancies, with roles in cell redox regulation and tumor progression (Paolicchi et al., Bioch. Pharm. 2002; Pompella et al., Curr. Op. Pharm. 2007). We have observed increased levels of DNA damage in GGT‐overexpressing cells, suppressed by specific GGT inhibitors, iron chelator DFO and lipid antioxidants. GGT is also implicated in drug resistance, as it favours the reconstitution of cellular glutathione. But the enzyme can actually play as a factor in drug sensitivity as well:i) protection offered by GGT against cisplatin depend on extra‐cellular reactions of cisplatin with GGT‐derived thiol metabolites (Franzini et al., EJC 2006, 42: 2623);ii) with 4‐[N‐(S‐glutathionyl‐acetyl)amino] phenylarsinous acid (GSAO) ‐ a promising anti‐angiogenic drug ‐ GGT activity acts as a sensitizing factor: GSAO is cleaved by GGT expressing cells, thus producing the active metabolite GCAO (Dilda et al., JBC 2008);iii) NO‐donor agents (e.g. S‐nitroso‐glutathione, GSNO) have been highlighted as "chemosensitizing agents". GGT selectively metabolizes GSNO (Angeli et al., ABB 2008), thus releasing its NO load: its expression may thus be exploited to target NO to GGT‐expressing tumor cells.Supported by Istituto Toscano Tumori (ITT, Firenze) and Fondazione Fibrosi Cistica (FFC, Verona) ‐ Italy.
Students and teachers reaching for the STARS: a cadaveric exploration of anatomy
Authors: Bruzzini Kristen Blake 
Published: June 2021

Area high school students and teachers had the opportunity to learn and teach human gross anatomy during an intensive workshop entitled Students and Teachers Anatomical Research Series (STARS) at Maryville University. Science teachers attended week one, which consisted of focused lectures on the anatomy of the thorax, abdomen, back, and upper and lower extremities, "hands‐on" cadaveric dissection, and development of lesson plans for use at home institutions. Week two involved putting into practice their new knowledge and teaching techniques. High school students spent this week performing traditional cadaveric dissection, as well as participating in either instructor assisted or self‐directed small group workstations using handouts, models and computer programs. Real world applicability of human anatomy was also incorporated. Daily assessment forms, end of course evaluations, and content testing of fourteen area high school students and two participating teachers demonstrated enthusiasm for the topics covered, an increased appreciation and understanding of the human body, and retention of the material covered at the end of the course. All teachers indicated that they learned information they would apply in their own courses and strongly felt that the workshop was an excellent opportunity for the university to generate an appreciation of anatomy and an excitement for learning at the high school level.Grant Funding SourceAmerican Association of Anatomists
An anatomy course based on clinical reasoning
Authors: Elizondo Omaña Rodrigo Enrique , Guzmán López Santos 
Published: June 2021

To describe a general view of how anatomy can contribute in an important way in the development of clinical reasoning.Learning based on clinical reasoning focuses in reaching an anatomical diagnosis out of any anomaly or normality. The basic intellectual abilities consist in the identification, description, comparison, definition and classification. The superior intellectual abilities are the analysis, synthesis and evaluation. Its systematic use allows the student to construct a mental structure for problem solving.An anatomical course based on clinical reasoning has two main objectives: favour anatomical knowledge acquisition and to make the student aware of the clinical reasoning process.
Neuroscience Teacher Training Workshops for Elementary School Teachers
Authors: Puder Barb 
Published: June 2021

A teacher training workshop was designed to instruct elementary school teachers regarding basic neuroscience content and provide guidelines for planning anatomical life science units for the classroom. This introduction of neuroanatomical sciences allows teachers to receive appropriate training in neuroanatomy, comply with the National Science Education standards, and create classroom activities that will encourage children to investigate topics regarding neuroscience.Two half day weekend workshops were implemented which included a neuroscience lecture. Following the lecture, teachers participated in a hands‐on laboratory session filled with activities and experiments that can be replicated in the elementary school classroom.To measure the impact and effectiveness of the workshop, participants were administered a pre and post test regarding key ideas presented in the workshop. Participants also filled out a survey rating the workshop's overall effectiveness, and course content. There was a statistically significant improvement from pretest to posttest (p< 0.0001).These workshops provided necessary teacher instruction in the anatomical sciences which promotes student interest in neuroscience.Supported by AAA Education Outreach Grant
Eukaryotic elongation factor 2 kinase (eEF2K) downregulation correlated with de novo DNA methylation and decreased DNA accessibility in neonatal IUGR rat liver
Authors: Fu Qi , McKnight Robert A , Yu Xing , Callaway Christopher W , Lane Robert H 
Published: June 2021

Uteroplacental insufficiency (UPI) alters protein synthesis in intrauterine growth restriction (IUGR). A key regulator of protein synthesis is eEF2K, which regulates protein synthesis by phosphorylating and inactivating eEF2. eEF2K is a classic CpG island gene. We hypothesized that UPI would affect hepatic eEF2K expression by altering eEF2K DNA methylation and possibly DNA accessibility in neonatal IUGR rats.MethodsIUGR rats were generated by bilateral uterine artery ligation. Nucleosome position and DNA accessibility was established by M.SssI methyltransferase (MMT) footprinting. EEF2K CpG methylation, mRNA and protein levels were determined.ResultsIUGR animals had decreased hepatic eEF2K mRNA and protein levels. 45 CpG sites around the transcription start site (TSS) from ‐282 through +217 on the eEF2K gene were analyzed. Increased CpG methylation between ‐206 and ‐282 occurred in IUGR relative to control. The position of 2.5 nucleosomes around the TSS was mapped by MMT footprinting. The ‐1 nucleosome was highly accessible in both groups, while ‐2 and +1 nucleosomes had significantly decreased accessibility in IUGR relative to control.ConclusionsUPI downregulates hepatic eEF2K expression in neonatal IUGR rats. This downregulation is correlated with de novo DNA methylation and reduced DNA accessibility. These results demonstrate IUGR induced alterations to nucleosome positioning.
Identification of Potential Enhancers in the RUNX1 Gene
Authors: Gutierrez Soraya Elisa , Rebolledo Boris , Stuardo Marcela , Martinez Milka , Lian Jane , Javed Amjad , Stein Gary , Stein Janet 
Published: June 2021

Human RUNX1 gene is the most frequent target for chromosomal translocations associated with acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL). The highest prevalence in acute myeloid leukemia (12‐15% of all cases) is noted with (8;21) translocation. Interestingly, all the breakpoints mapped to date in t(8;21) are clustered in intron 5 of the RUNX1 gene and intron 1 of the partner ETO gene. Even though, no homologous sequences have been found at the t(8:21) recombination regions; DNaseI hypersensitive sites (DHS) and topoisomerase II cleavage sites have been mapped to these areas of the genes. Presence of DHS sites is commonly associated with regulatory elements such as promoters, enhancers and silencers. In this study we used a combination of comparative genomics and chromatin analysis to identify transcriptionally active regions within intron 5 of the RUNX1 gene. Our genomic analysis identified nine potential enhancer regions that are evolutionarily conserved. Analysis of histone acetylation status of these regions in myeloid cells demonstrate a high association of 9,14 diacetylated histone H3; a hallmark of enhancer modules . Our results suggest that some of the identified conserved non coding sequences in the RUNX1 gene locus may act as regulatory sequences in hematopoietic cells.Grants: ACT 44; NIH R03 TW007170
Enhanced Detection of Low Abundant Molecules using Polymerized HRP Conjugates
Authors: Ganapathy Ramesh , Wolf Brian , Nlend Marie , Stanaitis Mike , Schofield Mark , Kilmer Greg , Desai Surbhi 
Published: June 2021

Enzyme conjugated secondary detection reagents are routinely used for amplified detection of specific antigens in immunoassays. Horseradish peroxidase (HRP) is the most widely used enzyme in ELISA, Western blotting, immunohistochemistry, Northern and Southern blotting applications and hybridization assays, because it is economical, robust and compatible with both insoluble and soluble substrates.We have developed a series of Streptavidin, Goat anti‐mouse (GAM) and Goat anti‐rabbit (GAR) Poly HRP for the detection of low‐abundant molecules. The new polymerized HRP conjugates are purified to remove unconjugated HRP, secondary detection reagents and monomer HRP conjugates.We have demonstrated increased sensitivity and signal intensity with the Thermo Scientific Pierce Poly HRP conjugates in ELISA, Western blotting and immunohistochemistry (IHC) applications. Human IFNγ and Bovine IL4 ELISAs using the Pierce Poly HRP conjugates displayed significant signal amplification over non‐polymerized and polymerized HRP conjugates. Western blotting and IHC detection of low abundant proteins displayed similar signal enhancement with Thermo Scientific Pierce Poly HRP conjugates.
Snack selection influences nutrient intake, metabolism and bowel habits in adult women
Authors: Howarth Leslie S. , Petrisko Yumi , Furchner‐Evanson Allison , Nemoseck Tricia , Kern Mark 
Published: June 2021

Since appropriate snacking may promote a healthy body weight and serve as an important contributor to a healthful diet for women, identification of suitable foods for inclusion between meals is essential. We investigated the influence of the incorporation of 100 kcal servings of snacks of dried plums versus commercial low‐fat cookies twice daily for two weeks with a two‐week washout period between trials on total energy and nutrient intake, biochemical parameters, and bowel habits. Twenty‐nine women aged 25‐54 years with a BMI between 24‐35 kg/m2 participated in a randomized, cross‐over fashion. Incorporation of dried plums or cookies into the diet did not alter energy intake or body weight; however, dried plums promoted greater (p=0.05) intake of fiber, potassium, riboflavin, niacin, and calcium compared to cookies. Total fat intake tended (p=0.094) to drop with dried plum consumption as did cholesterol intake (p=0.098). Plasma TG concentration increased (p=0.05) after consumption of cookies and was lower (p=0.05) for dried plums versus cookies. Dried plums promoted a softer (p=0.05) stool consistency compared to baseline and cookies. Subjects reported more complete evacuation of bowels (p=0.05) with dried plums versus cookies. These results suggest that dried plums improve blood lipids and diet quality and soften stools in comparison to a commercially processed snack.Supported by the CA Dried Plum Board.
China's Hypertension Increase Linked Significantly to Its Rapid Rise in Overweight: A 16‐year Longitudinal Analysis: China Health and Nutrition Survey, 1991‐2006
Authors: Du Shufa , Wang Huijun , Popkin Barry M 
Published: June 2021

While the rapid increases in stroke in China and hypertension across the developing world are understood, the underlying nutrition causes of this increase in hypertension are unexplored. Using longitudinal data on 8806 subjects aged 18 and older followed over six waves of the China Health and Nutrition Survey, we studied the effect of changes in weight on blood pressure and hypertension. Trained nutritionists obtained weighed dietary data over 3 days combined with individual 24‐h recalls. Trained physicians collected 3 measures of blood pressure over an hour, weight and height data with standardized methods. Multivariate longitudinal logistic regression models were used to estimate the relative risk, controlled for age, gender, education, and urban residence. Prevalence of overweight increased rapidly from 12.8% in 1991 to 27.2% in 2006 (faster among the poorest income tertile: 8% to 23.3%); prevalence of hypertension increased at the same pace from 15% to 27.8% (again fastest among the poorest tertile: 11.3% to 28.1%). Each additional kg of body weight was associated with a 9% increase in risk of being hypertension (RR=1.09, p<0.001). Sodium intake did not modify this relationship. Increased weight accounted for 3.7 per 100 individuals or 11% of the close to 13 percentage point increase in the prevalence of hypertension in China over this period.This research was supported by NIH R01‐HD30880.