bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETHINKING ANATOMY IN A COMPRESSED TIME FRAME: CLINICAL SYMPTOMS, NOT CASE STUDIES, AS THE BASIS FOR INTRODUCTORY INSTRUCTION IN GROSS ANATOMY
Authors: Zill Sasha 
Published: April 2020

The goal of this study was to develop effective approaches to train first year medical students in Gross Anatomy/Embryology in a compressed time frame. Pedagogical reorganization was based upon a core of clinical conditions taught in second‐year and Step One board review courses. These conditions were not presented as clinical problems (many students had limited prior training in medical terminology) but lectures and discussions focused upon clinical symptoms, allowing for a direct correlation of structure and function. Instruction in anatomy was extended to prepare for laboratory dissections. Overall methodology was multi‐modal, including 'flipped' and traditional lectures, guided study of prosections/radiographs and small group laboratory review sessions. Some content was reduced: knowledge of muscle actions and innervations was required, not origins and insertions. Performance in anatomy was specifically evaluated by computer‐based written examinations that included a set of questions (36) previously asked over a 7 year period (repetitively or with minor modification) and by regional practical exams. Mean scores in all areas were sustained or numerically improved, despite the compression of instruction duration. There were no significant differences in performance based upon question format (Basic science anatomy, Clinical Vignette) or instructional modality ('flipped' vs traditional lectures). Point biserial data indicated that students needing assistance in learning could still be identified. These results suggest that training in Gross Anatomy can be effectively maintained in a compressed duration by instruction in the context of symptomatology of clinical syndromes and conditions, a format that should also facilitate review for USMLE Step One Board examinations.Support or Funding InformationWVCTSI grant U54GM104942
Designing 3D Synthetic Matrices for Studying Interactions Between Bacterial Peptidoglycan and Macrophages in the Context of Immune Misrecognition Diseases
Authors: Wodzanowski Kimberly A. , Kloxin April M. , Grimes Catherine L. 
Published: April 2020

The immune system is a complex network comprised of various cellular components that work together to protect the body from damage, with a key function of differentiating between pathogenic bacteria and the 39 trillion commensal bacteria that constitute our microbiome. Misrecognition of commensal bacteria has been linked to many inflammatory bowel disorders in humans yet remains not fully understood and difficult to study. Enabled by recent advances in molecular tools, fragments of the bacterial cell wall peptidoglycan have been identified that bind to pattern recognition receptors within macrophages, which activate macrophages to start a signaling cascade that turns on the immune response. Typically, these interactions are studied using two‐dimensional invasion assays on tissue culture plastic plates; however, the dimensionality and ‘stiffness’ of these traditional culture systems may not be representative of the cell‐microenvironment interactions that exist in vivo. In order to better simulate the native cellular environment, three‐dimensional (3D) cell culture systems can be used to control key biochemical and mechanical properties of the cell microenvironment. Here, we established an approach for the encapsulation and culture of human macrophages in 3D within well‐defined, biomimetic hydrogels decorated with integrin binding peptides that mimic the natural in vivo environment and linked with cell‐degradable sites for cell‐driven migration and remodeling to probe macrophage response to bacterial invasion. With this approach, we have shown invasion with bacteria whose glycans are remodeled and their engulfment through immunostaining and assessed activation of macrophages using RT‐qPCR and ELISA. These studies provide new insights into the interactions between bacteria and immune cells and this new method affords unique opportunities for examining how our immune system recognizes and misrecognizes bacteria toward a better understanding of the mechanisms of immune misrecognition diseases.Support or Funding InformationNIH CBI Training Grant‐5T32GM008550NIH U01 Common Fund program‐U01CA221230‐01
Group A Streptococcus Prevents NOX‐2 Complex Formation to Limit Oxidative Burst in Macrophages
Authors: Mackey Kialani , Clark Mary , Lee Ryan C. , Yuen Isabelle , Okumura Cheryl Y.M. 
Published: April 2020

Group A Streptococcus (GAS) is a Gram positive bacterial pathogen responsible for about 500,000 deaths a year, causing diseases ranging from superficial pharyngitis to acute rheumatic fever. Immune cells such as macrophages and neutrophils generate reactive oxygen species (ROS) to aid in bacterial destruction. Unlike other bacterial species, GAS lacks enzymes that can detoxify ROS. We thus sought to determine whether GAS can prevent ROS production altogether. We found that THP‐1 macrophages infected with GAS indeed produce less ROS as measured by DCF‐DA assays. We next sought to determine whether GAS affect the formation of the NOX‐2 enzyme complex that produces ROS. The NOX‐2 complex is made up of cytosolic and membrane bound subunits that come together when activated by the phagocytosis of a pathogen. Analysis of whole cell lysates by Western blot indicate decreased NOX‐2 complex formation in GAS‐infected cells compared with controls. Furthermore, we analyzed recruitment of the cytosolic components to the phagosome membrane by analyzing crude cell fractions. These results confirmed that GAS infection prevents NOX‐2 complex assembly. Interestingly, our data indicates that GAS can not only prevent the formation of the NOX‐2 complex, but can disassemble the complex in stimulated cells. Our findings suggest that one way GAS evades defenses of our immune system is by preventing the formation of toxic ROS. Inducing ROS production in GAS‐infected cells would therefore provide an alternative to antibiotic treatment for GAS infections.Support or Funding InformationAmerican Heart Association (17GRNT3410851), Occidental College Undergraduate Research Center
Hormonal Regulation of Glycine Decarboxylase and its Impact on Cellular Physiology
Authors: Jog Ruta , Chen Guohua , Wang Jian , Leff Todd 
Published: April 2020

The amino acid glycine is involved in generation of multiple critical metabolites including glutathione, heme, and creatinine. Interestingly, in both humans and rodents, circulating glycine levels are significantly reduced in obesity, glucose intolerance, type II diabetes and non‐alcoholic fatty liver disease. The glycine cleavage system (GCS) is the predominant glycine degradation pathway in humans. The rate‐limiting enzyme of GCS is glycine decarboxylase (GLDC), and loss‐of‐function mutations of GLDC cause hyperglycinemia. Here, we show that GLDC gene expression is upregulated in livers of mouse models of diabetes and diet‐induced obesity as well as in the fasted state in normal animals. In exploring the hormonal signals that mediate these regulatory events we found that both glucagon and insulin stimulated GLDC gene expression. In primary rat hepatocytes, GLDC expression was strongly stimulated by glucagon and cAMP, and mildly with insulin while in a rat hepatoma cell line, insulin strongly stimulated GLDC expression as compared to cAMP. We identified the cAMP‐response element binding protein 1 (Creb1) and insulin responsive transcription factor Sterol regulatory element binding protein 1c (Srebp‐1c) as mediators of the glucagon and insulin stimulatory effect, respectively. By knocking down or overexpressing GLDC in cell lines we observed GLDC expression levels are strongly linked to intracellular glutathione and reactive oxygen species (ROS) levels. Our findings suggest that the hormonal regulation of GLDC may contribute to compensatory changes in glutathione production as a defense against metabolic disease‐associated oxidative stress.Support or Funding InformationThis work is supported by NIH R21AG050741, Grants Boost OVPR Wayne State University and the Michigan Diabetes Research and Training Center.
The effects of algae oil on laying performance, egg quality, adiponectin and hepatic lipogenesis in laying hens
Authors: Liao P.X. , Lin Yuan-Yu 
Published: April 2020

The purpose of current study is to explore the effects of algae oil on laying performance, egg quality, fatty liver syndrome and circulatory adiponectin in laying hens. Sixty‐four 26‐week‐old, Hy‐line W36 laying hens were allotted to two groups with 4 replicates, eight hens per replicate. The control group and the treatment group were fed basal diet with 3% soy oil and basal diet with 3% algal oil, respectively, totally for 4 weeks. The egg production rate and total egg weight per replicate were recorded every day. Egg quality, the fatty acids profile in yolk and cholesterol contents were measured every two weeks. Body weight and feed intake were recorded at beginning of experiment and week four. Blood samples were randomly taken from both groups (2 hens per replicate at week zero and four) . The level of macromolecule adiponectin and total adiponectin in plasma were analyzed. At last week of experiment, liver tissues were weighed and got liver biopsy. The results showed that treatment of algae oil did not affect laying performance and egg shell quality, but egg weight was significantly lighter in the treatment group. At week two, the width and height of yolk were significantly lower than the control group. At the result of histological examination, the accumulation of hepatic fat were significantly higher in the treatment group. The treatment of algae oil did not affect the level of macromolecule adiponectin and total adiponectin in plasma. The results showed that replacing soy oil with 3% algal oil in diets could accelerate the processes of fatty liver syndrome in chicken.Support or Funding InformationMinistry of Science and Technology, Taiwan (106‐2313‐B‐029 ‐003 ‐MY2)
The Biased Kappa Opioid Receptor Agonist Nalfurafine Reduces the Reinforcing Properties of Oxycodone and Enhances Oxycodone‐Induced Spinal Anti‐Nociception
Authors: Setola Vincent , White Allison , Wix Kimberley , Siderovski David Peter 
Published: April 2020

We recently described the effect of two G protein‐biased kappa opioid receptor agonists [1 mg ethoxymethyl ether (EOM)‐salvinorin B/kg and 15 μg nalfurafine/kg] on the reinforcing and anti‐nociceptive properties of co‐administered morphine (5 mg/kg) in mice (Kaski et al., JPET, 2019). EOM‐salvinorin B and nalfurafine each reversed the reinforcing properties of co‐administered morphine in the conditioned place preference paradigm, and each potentiated morphine‐induced spinal anti‐nociception in the warm‐water tail withdrawal paradigm. EOM‐salvinorin B had no effect on morphine‐induced supraspinal anti‐nociception in the hot‐plate paradigm; however, nalfurafine potentiated supraspinal anti‐nociception. In the current study, we addressed whether nalfurafine co‐administration (15 μg/kg) had similar beneficial effects on the prescription opioid painkiller oxycodone (2 mg/kg) in mice. Nalfurafine markedly reduced the reinforcing properties of oxycodone in the conditioned place preference paradigm. In addition, nalfurafine potentiated oxycodone‐induced spinal anti‐nociception in the warm‐water tail withdrawal paradigm. Nalfurafine did not affect oxycodone‐induced supraspinal anti‐nociception in the hot‐plate paradigm. Because nalfurafine has a decade‐long record of safety, tolerability, and long‐lasting efficacy (as an anti‐pruritic agent) in Japan, it is an attractive anti‐addictive, dose‐sparing adjuvant to conventional opioid painkillers that have shown tremendous addiction liabilities.Support or Funding InformationANW acknowledges support from the WVU SOM BBS T32 (1 T32 GM132494).
J‐Curve Effects on Basal Autophagy and ER Stress by Sympathetic Activation in the Vascular Endothelium
Authors: Tran Linh , Giles Jennifer , Callaway George , Wauson Eric , Tran Quang-Kim 
Published: April 2020

Activation of the sympathetic nervous system is important in the regulation of cardiovascular functions. Excess sympathetic nervous activity, however, is deleterious and is involved in pathological remodeling of cardiovascular tissues. The vascular endothelium is essential for the control of vascular tone, coagulation and metabolism and functions of other cardiovascular cell types. Basal autophagy is critical in maintaining the homeostasis of the endothelium. We hypothesized that long‐term adrenergic stimulation can impair basal autophagy and induce ER stress in the vascular endothelium. In freshly isolated aortic endothelial cells, norepinephrine (10−5 – 10−4 M for 1, 2, 5, 15, 24, 48 hrs) produced J‐curve effects on the autophagic markers, such that expression levels of LC3‐II and p62 are reduced following short‐term NE treatment, but are increased over time and significantly over control value following 48 hrs of treatment. Immunofluorescence showed increases in the numbers of LC3 and p‐62 puncta in cells treated with NE for 48 hrs. NE treatment also produces a J‐curve effect on the expression of ER stress markers calnexin and Ero‐1. Measurement of lysosomal pH indicates reduction in acidification of this compartment in cells treated with NE. Mechanistically, we hypothesized that NE affects basal autophagy via changes in mTOR activity. Indeed, a J‐curve effect was also seen with pS6, an mTOR activity marker, in endothelial cells treated with NE for 1, 2, 5, 15, 24, and 48 hrs. These data suggest that short‐term adrenergic activation stimulates basal autophagy, while long‐term sympathetic activation inhibits basal autophagy and induces ER stress, potentially via altering mTOR activity.Support or Funding InformationGrant IOER091707 to Quang‐Kim Tran; AHA grant 15SDG25090279 to Eric Wauson
Proenkephalin predicts organ failures, renal replacement therapy, and mortality in sepsis
Authors: Kim Hanah , Hur Mina , Lim Jihyang , Struck Joachim , Bergmann Andreas , Di Somma Salvatore 
Published: April 2020

IntroductionKidney failure frequently occurs in sepsis and is associated with high mortality. Proenkephalin (PENK) is an emerging biomarker for sepsis. We evaluated whether the PENK level could predict severity, organ failure, and 30‐day mortality in septic patients.MethodsThe PENK levels were measured using the sphingotest penKid assay (Sphingotec GmbH, Hennigsdorf, Germany) in a total of 215 septic patients. The PENK levels were analyzed in terms of sepsis severity, vasopressor use, 30‐day mortality, sequential (sepsis‐related) organ failure assessment (SOFA) renal subscore, the Chronic Kidney Disease Epidemiology Collaboration estimated glomerular filtration rate (CKD‐EPI eGFR) categories, and requiring renal replacement therapy (RRT). The number of organ failures, SOFA subscores, requiring RRT, and 30‐day mortality were compared according to the PENK quartiles.ResultsThe PENK levels were significantly higher in patients with septic shock, vasopressor use, and non‐survivors than in patients with solitary sepsis, no vasopressor use, and survivors, respectively (all P < 0.01). The PENK levels were significantly associated with SOFA renal subscore and CKD‐EPI eGFR categories (all P < 0.0001). The PENK quartiles were associated with the number of organ failures as well as SOFA renal, cardiovascular, respiratory, and central nervous system subscores (all P < 0.05). The PENK levels were significantly higher in patients who required RRT than in those who did not require RRT (P < 0.0001). High PENK level was also associated with high 30‐day mortality (P < 0.0001).ConclusionsPENK could be a useful and objective marker to predict severity, organ failure, and 30‐day mortality in septic patients.
INVESTIGATING MOTOR LEARNING IN A LRRK2 MOUSE MODEL OF PARKINSON’S DISEASE
Authors: Eby Allison , Crown Lindsey , Cowen Stephen 
Published: April 2020

While most cases of Parkinson’s disease are idiopathic, meaning of unknown origin, in 10% of cases, a genetic link has been identified. Of these, the most common is the G2019S mutation of the leucine‐rich repeating kinase 2 (LRRK2) gene. Investigation into this mutation could prove useful not only for those with LRRK2 Parkinson’s, but for idiopathic Parkinson’s as well. Genetic mouse models of this mutation are important for translational research, but despite the increasingly large number of studies on these animals, few have identified a reliable phenotype. In this study, we measured the average latency to fall during a rotarod‐based motor‐learning task conducted twice a week for two weeks with transgenic (Tg) and non‐transgenic (NTg) mice 6–8 months old. During the second week, half the animals were given a LRRK2 inhibitor, MLi‐2. Although we detected no effect of the drug, results have been mixed for overall motor performance with a trend towards LRRK2 Tg animals performing worse on the task. In this study, we examine whether LRRK2 Tg mice perform similarly to NTg mice for within‐day learning, between‐day learning, and overall latency to fall measures.Support or Funding InformationFunding from Michael J. Fox Foundation.
Hypoglycemic effect and hepato protective role of Saccharomyces boulardii THT 500101 strain in a murine model of streptozotocin‐induced diabetes
Authors: Cunha Tatiana Sousa , dos Santos Letícia Barssotti , Abreu Isabel Mallosto Emerich , Albuquerque Raquel Cristina Melo Ferreira , Brandão Ana Beatriz Pereira , Ferreira Fabiana Gomes , da Silva Dias Danielle , de Angelis Katia , Salgado Miguel Angel Castillo 
Published: April 2020

The chronic hyperglycemia of diabetes mellitus (DM) is associated with long‐term damage and dysfunction of different organs, including the liver. Hyperglycemia induces hepatic mitochondrial dysfunction causing changes that include decreased oxidative phosphorylation, increased oxidative stress, ultra‐structural abnormalities, which in turn worse metabolic health. The disturbance in metabolic homeostasis also modulates gut microbiota by a variety of mechanisms while the maintenance of intestinal microbiota has a significant influence on metabolic state. The aim of this study was to evaluate the hypothesis that streptozotocin‐diabetic mice treated with Saccharomyces boulardii THT 500101 strain (S. boulardii, THT: Probiotics and Starters Cultures, Belgium) present improvement of blood glucose, reduction of oxidative stress and maintenance of hepatocytes structure, concomitant with a beneficial impact in the gut microbiota profile. C57BL/6 male mice were randomly assigned into four groups: Control (C), Control + Probiotic (CP), Diabetes (D), and Diabetes + Probiotic (DP) (n = 9/group). Diabetic mice treated with S. boulardii presented a reduction of blood glucose (~30%) when compared to D group (DP = 251.9 ± 36.40 mg/dl vs. D = 362.9 ± 21.26 mg/dl, p<0.05). D group presented a higher level of carbonylated proteins compared with C and CP groups (C = 3.26 ± 0.42, CP = 3.00 ± 0.37 vs. D = 3.62 ± 0.33 nmol/mg), and probiotics reduced hepatic protein damage in DP (DP = 3.29 ± 0.58 nmol/mg). Diabetes reduced the activity of antioxidant enzymes superoxide dismutase (SOD) (D = 8.00 ± 0.12 vs. C = 8.49 ± 0.10, CP = 8.44 ± 0.05 USOD/mg, p<0.05) and glutathione peroxidase (GPx) (D = 73.50 ± 9.50 vs. C = 83.00 ± 4.00, CP = 81.00 ± 7.25 nmol/min/mg, p<0.05) and S. boulardii increased the activity of both enzymes in DP group as compared with D (SOD: DP =8.20 ± 0.14 USOD/mg and GPx: DP = 5.08 ± 2.29 nmol/mg, p<0.05). Signs of severe hydropic degeneration were noticed in hepatocytes from D group and to a lesser extent in hepatocytes from DP group. S. boulardii treatment was associated with increased proportion in Bacteroidetes, Firmicutes and Deferribacteres, and a decreased proportion of Proteobacteria and Verrucomicrobia phylum in DP group, as compared with D. Thus, the data presented here show up a novel potential therapeutic role of S. boulardii for glycemic control and attenuation of diabetes‐induced liver injury.Support or Funding InformationFAPESP 2016/24059‐2
Empagliflozin Prevents Renal Dysfunction and Inhibits Proximal Tubule NHE3 Activity in Nondiabetic Heart Failure Rats
Authors: Junior Flavio Araujo Borges , dos Santos Danubia Silva , Crajoinas Renato Oliveira , Wisnivesky Aline Cavalcantti T. , Benetti Acaris , Rios Thiago Matheus Santos , Antonio Ednei Luiz , Tucci Paulo , Girardi Adriana Castello Costa 
Published: April 2020

Sodium‐glucose cotransporter 2 (SGLT2) inhibitors improve glycemic control by suppressing glucose reuptake in the renal proximal tubule (PT). Primarily designed as antidiabetic agents, these drugs also reduce cardiovascular death and hospitalization for heart failure (HF), regardless of the presence or absence of type 2 diabetes. However, the mechanisms underlying the cardioprotective effects of SGLT2 inhibitors remain unknown. Given the importance of the cardiorenal axis in HF care, this study aimed to test the hypothesis that the SGLT2 inhibitor empagliflozin (EMPA) is capable of exerting renoprotective effects in the setting of nondiabetic HF. To this end, male Wistar rats were subjected to ligation of the anterior descending coronary artery or sham operation. Four weeks after surgery, rats were fed normal chow, with or without EMPA, for an additional 4 weeks. Compared with sham‐groups, HF rats treated with EMPA had similar serum BNP levels, whereas cardiac dysfunction deteriorated it further in HF rats (Sham: 0.5 ± 0.1; Sham+EMPA: 0.5 ± 0.1; HF: 2.1 ± 0.3; HF+EMPA: 0.9 ± 0.1 ng/mL). Additionally, HF rats exhibited an increase in lung (Sham: 3.2 ± 1.5; Sham+EMPA: 31.8 ± 1.1; HF: 44.7 ± 3.3; HF+EMPA: 32.7 ± 1.7 mg/mm) and right ventricle (Sham: 6.3 ± 0.2; Sham+EMPA: 5.2 ± 0.2; HF: 8.9 ± 1.0; HF+EMPA: 6.4 ± 0.3 mg/mm) mass. Renal function was impaired in HF rats as evidenced by low glomerular filtration rate (GFR) and high levels of plasma urea and urinary protein excretion. However, EMPA treatment restored these parameters to sham rats levels [(GFR, Sham: 6.5 ± 0.2; Sham+EMPA: 7.7 ± 0.6; HF: 4.5 ± 0.4; HF+EMPA: 7.7 ± 0.4 mL/min/kg) (Plasma urea, Sham: 37 ± 1; Sham+EMPA: 38 ± 2; HF: 48 ± 2; HF+EMPA: 39 ± 1 mg/dL) (Urine protein to creatinine ratio, Sham: 1.2 ± 0.1; Sham+EMPA: 1.0 ± 0.1; HF: 1.8 ± 0.1; HF+EMPA: 1.3 ± 0.1)]. Furthermore, EMPA prevented reduction of hematocrit in HF rats (Sham: 48.7 ± 0.3; Sham+EMPA: 49.5 ± 0.7; HF: 45.8 ± 0.5; HF+EMPA: 49.7 ± 0.4 %). In vivo stationary microperfusion showed that EMPA reduced Na+/H+ exchanger isoform 3 (NHE3) activity in HF rats, similar to sham‐groups (Sham: 2.05 ± 0.04; Sham+EMPA: 1.40 ± 0.05; HF: 4.36 ± 0.08; HF+EMPA: 1.54 ± 0.05 nmol/cm2). Collectively, these findings demonstrate that SGLT2 inhibition ameliorates renal dysfunction and improves the volemic status of nondiabetic HF rats.Support or Funding InformationSupported by FAPESP and CAPES.