bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of leucine aminopeptidase affects myocyte proliferation and differentiation
Authors: Osana Shion , Murayama Kazutaka , Suzuki Naoki , Takada Hiroaki , Kubota Takahiro , Nagatomi Ryoichi 
Published: April 2020

BackgroundLoss of skeletal muscle mass in the elderly, namely sarcopenia, is a rapidly growing global health problem. Understanding the mechanism of muscle mass regulation is essential to confront this problem. The balance of muscle protein synthesis and degradation is thought to be one of the key issues. Previous reports showed that muscle‐specific deletion of a crucial proteasomal gene, Rpt3 (also known as Psmc4), resulted in severe skeletal muscle atrophy (Kitajima Y et al., 2014). Although proteasomal proteolysis plays an essential role in the maintenance of muscle mass, the underlying mechanism remains unknown. Proteasome generates oligopeptides in the cytoplasm, which are further degraded quickly to amino acids depending on several aminopeptidases (Hershko A et al., 1992, Saric T et al., 2004). Although aminopeptidases may have a significant role in the maintenance of muscle mass, not much is known. Microarray analysis of transcripts in Rpt3 knockdown myocytes revealed an upregulated leucine aminopeptidase related genes. In this study, therefore, we examined the contribution of leucine aminopeptidase in the proliferation and differentiation of cultured myocytes.MethodsWe examined the consequence of leucine aminopeptidase inhibition on C2C12 myocytes under different culture conditions. Leucine aminopeptidase was inhibited by bestatin methyl ester (Bes‐ME; 100 μM), an aminopeptidase inhibitor. Proliferation was evaluated by counting the number of Ki67 (proliferation marker) positive cells. Differentiation was evaluated by myosin heavy chain (MyHC) staining and fusion index. Fusion index was calculated as the ratio of the nuclei number in myocytes with two or more nuclei versus the total number of nuclei. Additionally, phosphorylation of mammalian (or mechanistic) target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E‐binding protein (4EBP1), were evaluated by Western Blotting because they are key factors for muscle protein synthesis.ResultsLeucine aminopeptidase inhibition by Bes‐ME significantly suppressed the activity of leucine aminopeptidase. The proliferation of C2C12 myoblasts was significantly reduced and the differentiation of C2C12 myoblasts was also markedly restricted after Bes‐ME administration. The protein expression levels of MyHC, Myogenin, and MyoD responsible for myodifferentiation were also significantly reduced. Furthermore, we also discovered that the phosphorylation of mTOR was significantly suppressed after leucine aminopeptidase inhibition.ConclusionsLeucine aminopeptidase is essential for myoblast proliferation and differentiation; however, further studies are required to clarify the role of aminopeptidase in skeletal muscle growth.Support or Funding InformationAcknowledgementsThis work was supported by JSPS KAKENHI Grant Number 18H04080.
Siglec‐E Retards Atherosclerosis by Inhibiting CD36‐Mediated Foam Cell Formation
Authors: CHAU Lee-Young , Hsu Yaw-Wen , Chiang Ming-Tsai , Hsu Fu-Fei , Angata Takashi , Crocker Paul R. 
Published: April 2020

The accumulation of lipid‐laden macrophages, foam cells, within sub‐endothelial intima is a key feature of early atherosclerosis. Siglec‐E is a member of sialic acid binding lectin predominantly expressed on myeloid cells to transduce inhibitory signal upon interacting with its ligands. Whether Siglec‐E expression on macrophages impacts foam cell formation and atherosclerosis remains to be established. To this end, both apoE‐deficient and apoE/Siglec‐E‐double deficient mice were placed on high fat diet for 3 months and their lipid profiles and severities of atherosclerosis were then assessed. The results showed that Siglec‐E deficiency accelerated atherosclerosis without affecting lipid profile in apoE deficient mice. In vitro experiments demonstrated that Siglec‐E deletion facilitated the uptake of acetylated or oxidized low density lipoprotein (LDL) and augmented foam cell formation in macrophages. By performing proximity labeling and proteomic analysis, we identified CD36 as a cell surface protein interacting with Siglec‐E. Notably, the interaction between Siglec‐E and CD36 was not affected by the sialylation status of CD36. Further experiments demonstrated that oxidized LDL induced transient Siglec‐E phosphorylation and recruitment of SHP‐1 in macrophages. VAV, a downstream effector implicated in CD36‐mediated oxidized LDL uptake, was shown to interact with SHP‐1 following oxidized LDL treatment. Moreover, Siglec‐E deficiency enhanced VAV phosphorylation induced by oxidized LDL. Collectively, these data demonstrate that Siglec‐E attenuates atherosclerosis in apoE‐deficient mice through suppressing CD36‐mediated signaling responsible for modified LDL uptake and foam cell formation in macrophages.Support or Funding InformationThis work was supported by a grant from Ministry of Science and Technology of Taiwan (MOST‐106‐2320‐B‐001‐020‐MY3).
Biochemical Composition and Antimicrobial Activities of Seed Extracts of Avocado (Persea americana)
Authors: Akalazu Jacinta Ngozi , Uchegbu Rosemary Izunwanne 
Published: April 2020

Evaluation of the bioactive compounds present in plant extracts play an important role in developing effective antimicrobial agents that can combat resistant plant and animal fungal pathogens. The objectives of the study were to evaluate the biochemical composition and antifungal activities of Avocado (Persea americana) seed extracts. The fungal pathogens for the study were isolated from yam tuber. They were Botryodiploidia theobromae, Rhizopus stolonifer, Aspergillus flavus, Fusarium oxysporium and Geothricum candidum. Pathogencity tests showed that all the fungal isolates were pathogenic on the yam tuber. The results of the antifungal activity of Avacado pear seed using paper disc diffusion technique against the pathogenic fungi showed that it had varied degree of inhibitions on all the fungal pathogens, Botryodiploidia theobromae (13.20), Rhizopus stolonifera (14.02) A. flavus (12.10), F. oxysporium (9.30), G. candidum (7.00).Identification of antifungal compounds using GCMS revealed the presence of 119 compounds. The compounds with highest in abundance are 2‐n‐Octylfuran,this was followed by 13‐tetradecenal and 9,12‐Octadecadienoic acid and finally 2,15‐Octadecedien‐1‐ol acetate. It is suggested that Avacado pear seed be used on the treatment of plant and animal fungal diseases.Support or Funding InformationSelf
Similarities Between Stem Cell Niches in Glioblastoma and Bone Marrow: Rays of Hope for Novel Treatment Strategies
Authors: Hira Vashendriya , Breznik Barbara , de Jong Annique Loncq , Khurshed Mohammed , Molenaar Remco , Lah Tamara , van Noorden Cornelis 
Published: April 2020

Glioblastomais the most aggressive primary brain tumor. Slowly dividing and therapy‐resistant glioblastoma stem cells (GSCs) reside in protective peri‐arteriolar niches and are held responsible for GSC maintenance and glioblastoma recurrence. Recently, we showed similarities between GSC niches and hematopoietic stem cell (HSC) niches in bone marrow. Acute myeloid leukemia(AML) cells hijack HSC niches and are transformed into slowly‐dividing and therapy‐resistant leukemic stem cells (LSCs). Current clinical trials are focussed on removal of LSCs out of HSC niches to differentiate and to become sensitized to chemotherapy. In the present study, we elaborated further on these similarities by immunohistochemical analyses and fluorescence microscopy of17 biomarkers in paraffin sections of human glioblastoma and human healthy bone marrow. We found all 17 biomarkers to be expressed both in hypoxic peri‐arteriolar HSC niches in bone marrow and hypoxic peri‐arteriolar GSC niches in glioblastoma. Our findings implicate that GSC niches are being formed in glioblastoma as a copy of HSC niches in bone marrow. These similarities between HSC niches and GSC niches provide a theoretic basis for the development of novel strategies to force GSCs out of their niches, in a similar manner as in AML, to induce GSC differentiation and proliferation to render them more sensitive to anti‐glioblastoma therapies.Support or Funding InformationThis study was financially supported by the Dutch Cancer Society (KWF; UVA 2014‐6839 and UVA 2016.1‐10460), the European Program of Cross‐Border Cooperation for Slovenia‐Italy Interreg TRANS‐GLIOMA (Program 2017), the IVY Interreg Fellowship, the Slovenian Research Agency (Program P10245) and by the Fondation pour la Recherche Nuovo‐Soldati 2019.
Effective Antihypertensive Treatment with Epoxyeicosatrienoic Acid Analog (EET‐A) and 20‐HETE Antagonist (AAA) of Spontaneously Hypertensive Rats (SHR)
Authors: Gawrys Olga , Walkowska Agnieszka , Kompanowska-Jezierska Elzbieta , Husková Zuzana , Honetschlägerová Zuzana , Falck John , Imig John , Červenka Luděk 
Published: April 2020

IntroductionDespite decades of research the death toll of hypertension and associated disorders increases significantly each year. This impose the need to further determine the mechanisms underlying the development of hypertension and to implement more efficient therapeutic strategies. Growing number of research suggest the important role of cytochrome P‐450 dependent metabolites of arachidonic acid (AA) in blood pressure regulation. The epoxyeicosatrienoic acids (EETs) exhibit vasodilatory activity, they decrease sodium reabsorption and possess renoprotective and anti‐inflammatory properties. Considering the beneficial effects of EETs, we decided to test the efficiency of stable analog of 14,15‐EET [disodium (S)‐2‐(13‐(3‐entyl)ureido)‐tridec‐8(Z)‐enamido) succinate] called EET‐A, together with AAA [N‐disodium succinate‐20‐hydroxyeicosa‐6(Z),15(Z)‐diencarboxamide], a novel receptor antagonist of 20‐HETE which is another potent AA metabolite with both pro‐ and antihypertensive activity. To test the antihypertensive potential of both substances we employed spontaneously hypertensive rats (SHR), which are currently considered the best model to study human essential hypertension.MethodsMale SHR in the established stage of hypertension (16 week old) were treated for four weeks with EET‐A (n=8), AAA (n=6), as well as the combination of EET‐A and AAA (n=7) and compared to age‐matched untreated SHR (n=10) and WKY (n=5). Both tested substances were administered in drinking water in the dose of 10 mg/kg/day each. Systolic blood pressure (SBP) was measured by telemetry. Once a week observations in metabolic cages (food and water intake, feces, diuresis) were performed; urine, blood and tissue samples were collected for further analysis.ResultsEET‐A or AAA given alone had no significant effect on blood pressure of SHR. However, the combined treatment with AAA + EET‐A was significantly antihypertensive (161±5 vs 180±3 mmHg, p<0.05). Additionally, combined AAA and EET‐A attenuated cardiac hypertrophy expressed as left ventricle weight to tibia length (22.95±0.61 vs 24.75±0.35 mg/mm in untreated SHR, p<0.05), decreased kidney ANG II level, increased natriuresis and increased the excretion of nitric oxide metabolites (7.6±1.4 vs 4.8±0.7 μmol/24h in untreated SHR, p<0.05).SummaryTaking into account all the beneficial impact of the combined treatment with EET‐A and AAA on cardiovascular and renal function of adult SHR we suggest that it constitute a very promising novel antihypertensive strategy.Support or Funding InformationSupported by National Science Centre Poland (grant no 2017/26/M/NZ5/00367)and MH CZ ‐ DRO („Institute for Clinical and Experimental Medicine – IKEM, IN 00023001“)
Neuroanatomical Approaches to Improving Student Learning in Science Education
Authors: Azzam Mohammad , Easteal Ronald 
Published: April 2020

Students are usually led to believe that rote memorization is the best technique, and perhaps the only technique, to learn factual information. In disciplines such as Anatomy, and in science education generally, this belief is largely observed because factual information is constantly taught. This review challenges the said notion. First, the different stages of memory and its pathways are explained to provide the basis for the several teaching and learning paradigms which, if employed in the classroom, can improve student learning in science education. Next, the teaching and learning paradigms are described. These paradigms include cognitive load theory, dual encoding theory, the spiral syllabus, bridging and chunking during lectures, sleep consolidation, and retrieval practice. Although such paradigms are especially important in science education, they can be utilized in the teaching and learning of any discipline.Support or Funding InformationN/A
Comparative Effects of Taurine, Vitamin E and Nuclea latifolia (Stem‐Bark) Extract on Object Regonition and Anxiety on Wistar Rats Subjected to Water Immersion Restraint Stress
Authors: Iliya Ezekiel , Eze Ejike Daniel , Jiya Peter Babatsu 
Published: April 2020

Stress is the feeling of emotional or physical tension, that may arise from any event or thought that makes person become frustrated, angry, or nervous. Anxiety and cognitive impairment can be normal during stressful situations. The comparative effect of Taurine, Vitamin E, and Nuclea Latifolia (Stem back) extract object recognition and anxiety in wistar rats subjected to water immersion restraint stress was carried out. Total of twenty four rats weighing between 100g – 120 g were used for this study. The animals were divided into four groups before the commencement of the experiment as follows: Group A: Serves as the control and received 1ml/kg distilled water for three weeks. Group B: Received 0.2 ml/kg vitamin E for three weeks. Group C: Received 200 mg/kg taurine (TAU) for three weeks and Group D: Received 200 mg/kg of Nauclea latifolia (NL) (stem bark) extract for three weeks. At the end of the three weeks, animals were starved for 24 hours before the commencement of the stress procedure. They were anesthetized using chloroform vapour after which they were restraint on a wooden plank (25 by 19 cm) with the four arms anchored horizontally and were immersed into water up to the xiphoid level for two hours. After the stress procedure, object recognition task and anxiety behaviours were assessed. The result of the training phase on object recognition showed that, TAU group explored the novel object more (64.92 %) followed by Vit. E group (63.90 %). The NL group has the least percentage (52.75 %) in exploring the novel object that was presented to the animals. During the test phase, it was noticed that, the TAU together with Vit. E groups showed similar behaviour with that of the training phase as they explored the Novel object presented to them more (71.52 %) and (70.05 %) respectively. On the anxiety model, while the Vit. E group shows significant increase in the number of entries into the open arm, the Tau group revealed significant decrease in the number of entries into the closed arm. Vit. E, Tau and NL groups showed significant increase in time spent by the animals in the open arm. The researched therefore, showed that Taurine and Vitamin E improved object recognition in the rats and also inhibited anxiety‐like behavior in Wistar rats that were subjected to water immersion restraint stress.Support or Funding InformationPersonal Funding
Analysis of the Sural Nerve Complex in North American Adult Cadavers: Distribution, Population Specific Morphology, and Anatomic Variants.
Authors: Steele Robert , Coker Charles , Freed Blair , Brauer Phillip 
Published: April 2020

BACKGROUNDThe Sural nerve complex (SNC) consists of four components: the medial sural cutaneous nerve, lateral sural cutaneous nerve, sural communicating branch, and sural nerve proper. The sural nerve is a cutaneous nerve that innervates the distal posterolateral leg and dorsolateral foot. The SNC is highly variable and has six defined morphological types each representing different patterns in which the SNC can form the sural nerve proper. Because of variability amongst different populations the SNC may frequently become a site of iatrogenic injury.PURPOSEThe purpose of this study was to determine if the morphological type and spatial characteristics of the SNC we found in North Americans aligned with that described in the current literature.METHODSSix defined morphologic types of SNC have been described, each representing different patterns in which the SNC forms the sural nerve proper (Pirarvin, KR, Annals of Anatomy, 202, 36–44, 2015). Cadaveric data was obtained bilaterally in from 49 formalin‐ and three Thiel‐embalmed body donors (n=104 limbs) from KCUMB via superficial dissection methods revealing the SNC in the posterior leg. Measurements were obtained using forensic rules and calipers and documented using a digital camera. This study first approved by the KCUMB Institutional Biosafety Committee.RESULTSOur results showed a predominance of two major types of SNCs. In the first type (53%), the SNC originated from the lateral sural cutaneous nerve or common fibular cutaneous nerve. In the second type (34%), the SNC originated from the medial sural cutaneous nerve independent of the sural communicating branch, with or without the presence of lateral sural cutaneous nerve contribution. We also found a prevalence of bilateral asymmetry (67%) in the formation of the SNC. Lastly, were found higher frequencies of previously described SNC variants including connections of the SNC with the posterior femoral cutaneous nerve (30%) and terminal branches of the medial sural cutaneous nerve connecting with other cutaneous nerves adjacent the lateral malleolus (22%).CONCLUSIONOur data showed there are two prevalent forms of SNCs within the North American population and that bilateral asymmetry is more common than previously reported. A more complete understanding of the variation in the SNC is important for clinical electrophysiology evaluations, neurological disease testing, lower extremity tissue repair, and sural nerve use in autogenous nerve grafts.
ROLE OF TYROSYLPROTEIN SULFOTRANSFERASE 2 (TPST2) IN PANCREATIC CANCER
Authors: Cai Xinran , Xie Wen 
Published: April 2020

Pancreatic cancer is an aggressive disease which has become the third leading cause for cancer deaths in the United States. Tyrosylprotein sulfotransferase 2 (TPST2) is a post‐translational modification enzyme which locates in the trans‐Golgi apparatus and catalyzes the sulfation of proteins’ tyrosine residues. Moreover, tyrosine sulfation has been shown to play a critical role in protein‐protein interaction. By analyzing TCGA data, we found that the expression of several known substrates of TPST2 were affected in pancreatic cancer. However, whether TPST2 affects cancer cell behavior is unclear. To determine the role of TPST2 in pancreatic cancer, MTT cell growth assay and soft agar colony formation assay were performed to assess cancer cell proliferation in MiaPACA2 and PANC‐1 human pancreatic cancer cell lines. Migration and invasion of cancer cells in vitro were evaluated by transwell assay. CRISPR‐Cas9 was utilized to establish TPST2 KO stable cell lines. Total RNA‐seq analysis was performed to analyze the transcriptome in the TPST2 KO and control cells. We showed that knockdown of TPST2 inhibited the proliferation of pancreatic cancer cells both in vitro and in vivo. Knockdown of TPST2 also decreased migration and invasion of pancreatic cancer cells in vitro. RNA‐seq analysis revealed that the extracellular matrix (ECM) receptor interaction pathway was significantly downregulated in TPST2 KO cells. We further demonstrated that expression of intergrin beta 4 (ITGB4), a protein involved in ECM receptor interaction pathway, was decreased when TPST2 was knocked‐down or inhibited. Our studies have uncovered the role of protein sulfation in pancreatic cancer and may establish TPST2 as a therapeutic target for pancreatic cancer.Support or Funding InformationThis work was supported in part by National Institutes of Health grants DK083952, ES023438 to Wen Xie.
Effects of Fat Tissue on Chronic Muscle Injuries
Authors: Quigley Mikayla , Kopinke Daniel 
Published: April 2020

During aging and certain muscle diseases such as Duchenne Muscular Dystrophy (DMD), muscle mass declines and is being replaced with fat tissue in a process called fatty degeneration. However, it is unclear if intramuscular fat plays an important role in the initiation and/or progression of fatty degeneration. Recent data suggests that when the fat fraction is greater than 0.5, over half of DMD patients are no longer able to walk. Based on these observations we, therefore, hypothesize that an increase in fat could impair muscle regeneration and function in chronic injuries. In young and healthy muscles, satellite stem cells are required for regeneration. Fibro/adipogenic progenitors (FAPs), which can differentiate into fat tissue and produce fibrotic scar tissue during chronic injuries and aging, aid in the healing process of muscle injuries. While beneficial, the exact relationship between FAPs and satellite stem cells during muscle regeneration is unclear. The purpose of this project was to establish a novel mouse model enabling us to conditionally prevent the differentiation of FAPs into adipocytes to determine the functional role of fat. To prevent FAPs from turning into fat, we conditionally deleted Pparγ, the master regulator of adipogenesis, using the Cre‐LoxP system in the mouse (Pparγ cKO). To induce fat formation, I injected 50% Glycerol into the tibialis anterior muscle, which causes muscle fiber loss and replacement with adipocytes. I stained adipocytes with PERILIPIN via immunofluorescence and quantified the amount of fat that was present in Pparγ cKO and control mice to determine if fat formation was indeed repressed after loss of Pparγ. I found a strong reduction in the amount of adipocytes, which have formed 21 days after a Glycerol induced injury in Pparγ cKO compared to control mice, arguing for efficient repression of adipogenesis. I also looked at fibrosis through Sirius Red staining to determine if the decrease in fat cells resulted in an increase of FAPs developing into fibrotic scar tissue. However, I saw no significant difference in fibrotic tissue between control and Pparγ cKO mice, suggesting that the prevention of fat formation does not cause an increase in the presence of fibrotic tissue.Thus, our new mouse model successfully blocks fat formation without increasing fibrotic scar tissue. In the future, this new mouse model will allow us to determine if the prevention of fat in a chronic muscle disease model, such as the mouse model for Duchenne Muscular Dystrophy, will have a positive effect on muscle repair and function.Support or Funding InformationStart‐up grant given to Daniel Kopinke; ASPET SURF Program at the University of Florida funding to Mikayla Quigley