bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anatomical Variation of Tendinous Interconnection between Flexor Hallucis Longus and Flexor Digitorum Longus Tendon and Its Location regarding Master Knot of Henry
Authors: Wan-ae-loh Perin , Dangintawat Pimpimol , Huanmanop Thanasil , Agthong Sithiporn , Chentanez Vilai 
Published: April 2020

Tendinous interconnections between flexor hallucis longus (FHL) and flexor digitorum longus (FDL) have functional importance in toe movement and act as a natural tenodesis after harvesting FHL tendon proximal to master knot of Henry (MKH). This anatomical study aimed to clarify the type, location and distribution to lesser toes of tendinous interconnection between FHL and FDL tendons in 102 embalmed and 62 soft cadaveric feet. According to the classification of Beger et al., three types of interconnection (type I, II, V) were found in 85.4 %, 0.6%, and 7.9% of specimen, respectively. In addition, a new type of connection (6.1%) in which is FHL tendon bifurcated into one tendon to the first toe and the other tendon fused with FDL tendon. The tendinous interconnection was located either proximal (−) or distal (+) to MKH. The mean distance from MKH in type I was1.38±10.40 mm (from −59.47 to 20.52 mm). The proximal and distal interconnection slips in type V were located at 6.61±4.69 mm (from 0.00 to 12.47mm) and 12.95±3.48mm (from 7.05 to 16.13 mm) from MKH. In the new type, the interconnection slip was located at −6.59±8.93 mm (from −20.81 to 5.48 mm) from MKH. The distribution of tendinous slip to lesser toes was determined by pulling the FHL tendon and observing the lesser toes’ movement. According to the classification of Plaass et al., the prevalence of distribution of tendinous slip to lesser toes in type a, b, c and d was 19.5%, 67.7%, 11.0%, and 1.8%, respectively. Knowledge of the tendinous interconnection and its location are important for enhancing the clinical efficacy of FHL tendon transfer and minimizing of the functional loss of toes in post‐operative period.Support or Funding Information1. The ๑ ๐ ๐ th Anniversary Chulalongkorn University Fund for Doctoral Scholarship from the Graduate School, Chulalongkorn University 2. Overseas Academic Presentation Scholarship for Graduate Students from the Graduate School, Chulalongkorn University
Role of Mineralocorticoid receptor (MR) and NEDD4‐2 in the regulation of ENaC and ROMK in the Distal Convoluted Tubule (DCT) and Cortical Collecting Duct (CCD)
Authors: Zhang Dandan , Wu Peng , Duan Xin-Peng , Lin Dao-Hong , Staub Olivier , Ellison David H. , Wang Wen-Hui 
Published: April 2020

BackgroundENaC and ROMK (Kir1.1) are expressed in the apical membrane of aldosterone‐sensitive distal nephron (ASDN). Aldosterone has been shown to play an important role in the regulation of ENaC and ROMK expression in ASDN. Also, NEDD4‐2 is an E3 ubiquitin ligase expressed in the ASDN and NEDD4‐2 has been shown to play a role in mediating the effect of aldosterone on ENaC. The aims of the present study are:1) To examine whether MR plays a similar role in regulating ENaC and ROMK in the DCT2 and CCD; 2) To examine whether NEDD4‐2 regulates ROMK channels in ASDN.MethodsThe whole‐cell recording technique has been used to measure the amiloride‐sensitive Na currents (ENaC) at −60 mV and TPNQ‐sensitive K currents (ROMK) at −40 mV in the DCT2/early connecting tubule (CNT) and in the CCD of tubule‐specific MR‐KO, NEDD4‐2 KO and corresponding WT mice on a normal rodent diet (0.4% Na and 0.9% K).ResultsDeletion of MR receptor decreased ENaC currents from10.2 pA/pf to 6.3 pA/pf (at −60 mV) in the DCT2/CNT but it largely abolished ENaC currents in the CCD (from 4.9 pA/pf to 0.7 pA/pf). In contrast, the deletion of MR had no significant effect on ROMK currents in the DCT2 since TPNQ‐sensitive K currents were the same between WT and Ks‐MR‐KO mice (WT, 51.0 pA/pf; Ks‐MR‐KO, 50.0 pA/pf at −40 mV). However, the ROMK currents of the CCD were significantly smaller in MR‐KO (22.1 pA/pf) than in WT (33.8 pA/pf), suggesting that MR plays a role in regulating ROMK only in the CCD but not in the DCT2/CNT. Deletion of NEDD4‐2 increased amiloride sensitive Na currents from 10 pA/pf to 13 pA/pf in the DCT2/CNT but it robustly increased ENaC currents from 5.1 pA/pf to 15 pA/pf in the CCD, suggesting that NEDD4‐2 plays a bigger role in regulating ENaC in the CCD than in the DCT2/CNT. Deletion of NEDD4‐2 inhibited rather than stimulated ROMK channel activity in both DCT2/CNT and in the CCD. TPNQ‐sensitive K currents were decreased from 46 pA/pf (WT) to 24.6 pA/pf (NEDD4‐2 KO) in the DCT2/CNT and from 34 pA/pf (WT) to 23.6 pA/pf (NEDD4‐2) in the CCD.ConclusionMR plays a key role in the regulation of ENaC in the CCD but to a less degree in the DCT2/CNT. ROMK channel activity is modestly regulated by MR in the CCD but not in the DCT2/CNT. NEDD4‐2 plays a role in the down‐regulation of ENaC activity in the ASDN, especially in the CCD, but it may not directly regulate ROMK.Support or Funding InformationDK54983
Methionine Aminopeptidase Inhibitors in Mammalian Cells
Authors: Condic Natalia , Ramtahal Cassandra , Boukari Jamila , Croes Alex , Nguyen Calvin , Alvarez Melissa , Olaleye Omonike , Rosell Rosemarie 
Published: April 2020

Mycobacterium tuberculosis (Mtb) is the leading cause of mortality from an infectious disease, worldwide. Mtb benefits from an HIV‐weakened immune system, and leads to a statistically increased risk of HIV/TB co‐infection. The rise of multi‐drug resistant Mtb strains makes treatment difficult, thus a novel drug may be required to eliminate Mtb infection. Our collaborators at Texas Southern University have identified novel bacterial methionine aminopeptidase (MtMetAP1) inhibitors. Genetic knockout studies support the lethality of the deletion of MtMetAP1 in Mtb. Further studies support the existence of an ortholog of MtMetAP1 in Homo sapiens (HsMetAP1). In addition, humans have several paralogs of MetAP, which perform similar essential functions to MetAP1. Although these novel inhibitors are effective against Mtb, the cytotoxicity in mammalian cells has not been established. To address this, we tested a MtMetAP1 inhibitor (UST‐001) on H1299 human lung carcinoma cells and Mlg‐2908 mouse lung fibroblast cells. Using flow cytometry and a WST‐1 assay to assess cell viability, we determined the LC50 to be 1.652μM in the H1299 lung carcinoma cell line. The consistent non‐significance of our data supports our hypothesis regarding the non‐fatal nature of this drug in a human cell line, as there were no significant differences between controls and experimental conditions. Initial results from WST‐1 assays with Mlg‐2908 cells indicate that the LC50 for Mlg‐2908 is between 5 and 10μM, higher than that of H1299. Further studies using flow cytometry analysis are required to solidify this comparison, while another apoptotic assay may also be beneficial to determine an exact LC50 and ultimately the efficacy of this drug.Support or Funding InformationU.S. DOE, Hispanic‐Serving Institutions, STEM Articulation Grant P031C110128, the Cullen‐Smith Foundation, and the UST Committee for Student Research for their financial support
Down Regulation of HMGB1‐RAGE pathway by Ethyl Pyruvate
Authors: Mun Seok-Jun , Yang Chul-Su 
Published: April 2020

HMGB1 (high Mobility Group Box 1) protein is released by nuclear after that binds to DNA. HMGB1 can also be secreted from cells, it can bind receptor for advanced glycation end products (RAGE) that inflammatory receptor. Interaction between HMGB1 and RAGE causes upregulation of NF‐kB that leads to increased production of cytokines. Ethyl pyruvate (EP) is the ethyl ester of pyruvic acid. In recent research, EP has shown HMGB1 inhibitory effecting in many inflammation‐related diseases through pathway inhibition. In this study, we measured that expression of HMGB1 mRNA and proteins stimulated by LPS in presence of ethyl pyruvate (EP) or other inflammatory stimulants was measured as RT‐qPCR and immunoblotting analysis in BMDMs. Furthermore, levels of cytokine in the supernatant of BMDM stimulated by LPS in presence of EP or other inflammatory stimulants or mouse serum were measured by ELISA. Here in we found that EP inhibits HMGB1 pathway leading to reduced RAGE expression and NF‐κB activation. Moreover, we demonstrated EP reduced HMGB1 in serum levels of mice. Our results suggested that EP is effective inhibitors of HMGB1/RAGE signaling pathway, offering a novel potential therapeutic approach to patients and HMGB1 has been proposed as a target for inflammatory disease.Support or Funding InformationACKNOWLEDGEMENTSThis work was supported by the NRF grant funded by the Korea government (MSIP) 2019R1I1A2A01064237.
MMP9 inhibition increases autophagic flux in chronic heart failure
Authors: Nandi Shyam S. , Katsurada Kenichi , Sharma Neeru M. , Anderson Daniel R. , Mahata Sushil K. , Patel Kaushik P. 
Published: April 2020

An increased matrix metalloprotease 9 (MMP9) during post‐myocardial infarction (post‐MI) exacerbates ischemia‐induced chronic heart failure (CHF). MMP9 abrogation is cardioprotective during post‐MI remodeling, however, whether MMP9 abrogation protects the heart via upregulation of autophagic activity is unknown. This study aimed to determine whether the MMP9 inhibition upregulates cardiac autophagic flux during post‐MI CHF in rats. Sprague‐Dawley rats underwent either Sham or coronary artery ligation, 6–8 weeks prior to being treated with MMP9‐inhibitor for 7 days, followed by cardiac autophagic flux measurement using lysosomal inhibitor BafilomycinA1. Further, autophagic flux was measured in vitro by treating H9c2 cardiomyocytes with two independent pharmacological MMP9 inhibitors, Salvianolic‐Acid‐B (SalB) or MMP9‐inhibitor‐I and CRISPR/cas9–mediated MMP9 genetic ablation. CHF rats showed cardiac infarct, significantly increased left‐ventricular end diastolic pressure (LVEDP), and increased MMP9 activity and fibrosis in the peri‐infarct areas of left‐ventricular myocardium. The autophagic markers LC3B‐II and p62 measurement with lysosomal inhibition showed decreased autophagic activity in the peri‐infarct myocardium. Treatment with SalB for 7 days in CHF rats decreased MMP9 activity, cardiac fibrosis, and increased autophagic flux in the peri‐infarct myocardium. As an in vitro corollary study, measurement of autophagic flux in H9c2 cardiomyocytes showed that pharmacological inhibition or genetic ablation of MMP9 upregulates autophagic flux. These data are consistent with our observations that MMP9 inhibition upregulates autophagic flux in the heart of rat with CHF. In conclusion, the results in this study suggest that the beneficial outcome of MMP9 inhibition on pathological cardiac remodeling is in part mediated by improved autophagic flux.Support or Funding InformationThis work was supported by American Heart Association Career Development Grant Award 19CDA34490029 to S.S. Nandi, and National Institutes of Health Grants R01‐DK‐114663, P01‐HL‐62222, and endowed McIntyre Professorship to K.P. Patel.
A Mixed Reality Application To Visualize Amino Acids
Authors: Srinivasan Rekha , Ali Ridaa 
Published: April 2020

This study examines the benefit of using mixed reality to visualize amino acid molecules for students in introductory biochemistry courses at the undergraduate and graduate level. A Novel Microsoft HoloLens application that tests understanding of amino acid structures was developed. The application was made accessible to students by making it compatible with multiple platforms in addition to Universal Windows Platform; these platforms include Android and iOS as well as PC, Mac, and Linux stand‐alone. This was done using Unity3D with coding in C#. The success of application development and implementation in the classroom was tested by students of Biochemistry. The results of student attitude survey regarding the ease and benefit of the application on mixed reality, and any other platforms they choose to use it on, is presented hereinSupport or Funding InformationPRISE, WISER, Flora Stone Mather Center for Women, Case Western Reserve University
Melatonin Mitigates Ovarian Toxicity In Cannabis‐treated Female Wistar Rats
Authors: Olayaki Luqman Aribidesi , Oluwasola Amuda 
Published: April 2020

OBJECTIVESThis study investigated the effects of Cannabis sativa (CS) and melatonin on oestrus cycle, ovulation and reproductive hormones.METHODSTwenty female rats were assigned into four groups of five animals each, such that the rats received orally 1mL distilled water, 2mg/kg body weight (BW) of CS, 2mg/kg BW of CS plus 4mg/kg BW of melatonin and 4mg/kg BW of melatonin, respectively. Vaginal smears were taken daily to determine the stages of oestrus cycle. Ova counts were done according to the method described by Kim et al., 1994. Gonadotropin releasing hormone (GnRH), Luteinising hormone (LH), follicle stimulating hormone (FSH), oestradiol (E) and progesterone were determined using standard methods.RESULTSCS significantly (p<0.05) lengthened the metestrus and dioestrus phases of oestrus cycle. However, it significantly (p<0.05) shortened the proestrus and estrus phases respectively. There was significant (p<0.05) decrease in the ova count of the cannabis‐treated group when compared with the control and other treatment groups. In addition, animal treated with CS significantly (p<0.05) decreased the GnRH, FSH, LH, E and progesterone levels respectively. All these effects were ameliorated when combined with melatonin to the level comparable to the control.CONCLUSIONThis study showed some of the gonadotoxic effects of CS which could be mediated by endocrine disruption. However, these effects could be ameliorated by melatonin.
Crystal structure of the human phospholipase D1 catalytic domain provides insight into activation by PI(4,5)P2 and RhoA
Authors: Airola Michael V. , Bowling Forrest , Salazar Christian , Frohman Mike 
Published: April 2020

The signal transduction enzyme phospholipase D1 (PLD1) hydrolyzes phosphatidylcholine to generate the lipid second‐messenger phosphatidic acid, which plays roles in disease processes such as thrombosis and cancer. PLD1 is directly and synergistically regulated by Protein Kinase C, ARF and Rho GTPases, and the membrane lipid phosphatidylinositol‐4,5‐bisphosphate (PIP2). Here, we present a 1.8Å‐resolution crystal structure of the human PLD1 catalytic domain that is characterized by a globular fold with a funnel‐shaped hydrophobic cavity leading to the active site. Adjacent is a PIP2‐binding polybasic pocket at the membrane interface that is essential for activity. The C‐terminus folds into and contributes part of the catalytic pocket, which harbors a phosphohistidine that mimics an intermediate stage of the catalytic cycle. Mapping of PLD1 mutations that disrupt RhoA activation identifies the RhoA‐PLD1 binding interface. This structure sheds light on PLD1 regulation by lipid and protein effectors, enabling rationale inhibitor design for this well‐studied therapeutic target.Support or Funding InformationThis work was supported by the NIH awards: R35GM128666 (MVA), T32GM092714 (FZB), and R01GM084251 (MAF), and the NSF award: 1612689 (CMS).
Angiotensin 1‐7 reduces muscle atrophy and function loss following 16 week denervation
Authors: Renaud Jean-Marc , Albadrani Hind 
Published: April 2020

Muscle atrophy is defined as a decrease in muscle mass that eventually leads to partial or complete muscle wasting. Muscle atrophy occurs in a variety of conditions including chronic diseases, limb immobilization and following a complete loss of muscle activity after spinal cord injury and peripheral nerve injury. A consequence of muscle atrophy is large force decrease associated with muscle mass loss as well as contractile components. The objective of this study was to determine whether angiotensin 1‐7 reduces the atrophy process and force loss following muscle denervation. Mouse extensor digitorum longus (EDL) and soleus were denervated by removing 3–4 mm of the sciatic nerve at the thigh level. Denervated mice were divided into 4 groups: i) denervated; ii) denervated and treated with angiotensin 1‐7; iii) denervated and treated with diminazene aceturate (DIZE), a ACE2 activator, to locally increase Ang 1‐7 levels, and iv) denervated and treated with sucrose. A 5th group of mice was used as control, i.e., normal innervated muscle. The results show that angiotensin 1‐7 significantly prevented muscle mass loss and fully prevented the loss of normalized force to cross sectional area that normally occurs over a 16 week denervation period. The maintenance of the normalized maximum force by angiotensin 1‐7/DIZE was in part due to a prevention of the loss of membrane excitability that occurs because denervated fibers are depolarized. This study is thus providing evidence that angiotensin1, 7 has therapeutic potential to prevent function loss following prolonged denervation.Support or Funding InformationThis project was supported by a grant from the National Science and Engineering Research Council of Canada (NSERC).
Chronic Stress Induces Persistent Hypertension and Increases NMDA Receptor Activity in the Paraventricular Nucleus in Borderline Hypertensive Rats
Authors: Zhou Jing-Jing , Shao Jian-ying , Chen Shao-Rui , Li De-Pei , Pan Hui-Lin 
Published: April 2020

Stress activates sympathetic outflow and promotes hypertension development in humans with genetic predisposition. The enhanced N‐methyl‐D‐aspartate receptor (NMDAR) activity in the hypothalamus paraventricular nucleus (PVN) plays a critical role in controlling sympathetic output in hypertension. However, it is unclear how chronic stress affects NMDAR activity in the PVN in borderline hypertensive rats (BHR). BHR are the F1 male offspring from crossing female spontaneously hypertensive rats with male Wistars Kyoto rats (WKY). Arterial blood pressure (ABP) was monitored in free moving rats by using radiotelemetry. Using a 6‐week chronic unpredictable stress protocol, we found that stressed WKY rats had increased ABP during chronic stress but ABP returned to the normal level within a few days after stress. However, the stressed BHR showed a greater increase in ABP during stress and the elevated ABP was sustained for at least 2 weeks after discontinuing stress. Furthermore, whole‐cell voltage clamp recording in brain slices showed that the amplitude of evoked‐NMDAR currents in spinally projecting PVN neurons was significantly higher in stressed BHR than in non‐stressed BHR controls. Inhibiting α2δ‐1 with gabapentin normalized the increased synaptic NMDAR activity of spinally projecting PVN neurons in stressed BHR. In addition, the expression level of GluN1 and α2δ‐1 in the PVN was significantly greater in stressed BHR than in stressed WKY or non‐stressed BHR. These results suggest that chronic stress induces persistent hypertension in BHR, which is associated with α2δ‐1‐mediated NMDAR hyperactivity in PVN presympathetic neurons.Support or Funding InformationAcknowledgmentsSupported by NIH grants HL131161 and HL142133.
Anatomical Characterization Of Gαi2 Expressing Hypothalamic Paraventricular Nucleus Neurons
Authors: Chaudhary Parul , Wainford Richard D. 
Published: April 2020

BackgroundHypertension is a global health burden, and excess dietary salt is an established cause of hypertension. The hypothalamic paraventricular nucleus (PVN) is an essential component of the neuronal network that regulates sodium homeostasis and blood pressure. Previously, we have shown PVN specific GPCR‐coupled Gαi2 subunit proteins are essential to counter the development of salt‐sensitive hypertension by mediating the sympathoinhibitory and natriuretic responses to increased dietary sodium intake to maintain sodium homeostasis and normotension. However, the cellular localization and identity of PVN Gαi2 expressing neurons is currently unknown.ObjectiveTo determine the anatomical characterization of Gαi2 expressing PVN neurons.MethodologyThree‐month‐old male (n=3) and female (n=3) Sprague Dawley rats were subjected to transcardial perfusion, and brains were post fixed in 4% paraformaldehyde and 30% sucrose. 20μm frozen brain slices were collected. Using in‐situ hybridization (ACD RNAscope kits) neuronal expression of Gαi2, vGLUT2, GAD67, corticotropin‐releasing hormone (CRH), tyrosine hydroxylase (TH), oxytocin, and arginine vasopressin (AVP) in hypothalamic PVN neurons was determined. The visualization and evaluation of co‐localization of Gαi2 expressing PVN parvocellular neurons with vGLUT2, GAD67, CRH, TH, oxytocin and AVP was done using a Keyence Bz‐9000e microscope and Image J respectively.ResultsWe observed no differences among male and female rats, therefore, all data is presented as n=6. Our data show that neurons containing Gαi2 mRNA are localized in parvocellular but not magnocellular region of hypothalamic PVN. In the parvocellular region Gαi2 mRNA co‐localized with 87.5 ± 3.0% of GABA expressing neurons and 25.1 ± 2.7 % of vGLUT2 neurons, signifying that the Gαi2 mRNA is highly co‐localized with GABAergic neurons. Additionally, Gαi2 co‐localized with 76.3 ± 5.2% of CRH neurons and 33.5 ± 1.8% of TH expressing parvocellular neurons. We observed no localization of Gαi2 neurons with oxytocin or AVP expressing magnocellular neurons.ConclusionGiven 1) our prior data demonstrate PVN Gαi2 proteins play a critical role in mediating sympathoinhibition and, 2) that the GABAB receptor signals predominantly through a Gαi2 pathway we speculate, given the high co‐localization of Gαi2 mRNA with GABAergic neurons, that Gαi2 proteins modulate GABAergic signaling to impact sympathetic outflow and blood pressure.Support or Funding InformationT32 HL007224 to PCR01 HL139867 to RDWR01 HL141406 to RDWR56 AG057687 to RDW