Digital Commons Network^™

Rmdc Edition 2014

Metro Denver Dental Society Articulator Magazine

The MDDS Articulator magazine has been serving as the voice for Denver's dental community for over 100 years.

Distributed to approximately 2,000 dental professionals quarterly, the Articulator features local news, industry trends, practice management guidance, data-driven research and more. The award-winning publication is available to member dentists in both print and digital forms.

Issues include cover and feature articles alongside regular columns with regional news impacting the Metro Denver membership including editorial and perspectives columns, legal, association activities, component news, continuing education opportunities, and classifieds.

Innovation With Information Technologies And Using Nostalgia As An Organizational Strategy, Mojdeh Pajoutan, Chad Seifried

Journal of Applied Sport Management

The purpose of this paper is to show how sport organizations can use innovation through information technology (IT) to support the pursuit of nostalgia by revenue-oriented sport organizations as an organizational strategy to improve or maintain their fan nation. Collectively, a five-stage flowchart is offered that demonstrates an innovation process using IT for nostalgia to improve the placement of sport organizations in competitive markets. The foundation for this work’s approach is based on expanding Damanpour and Schneider’s (2006) three stages of innovation process in organizations, which include 1) initiation, 2) adoption decision, and 3) implementation. Wolfe’s (1994) “process of innovation” …

Mycoplasmas & Mycobacteria: Minimalists At Work, Shalee Killpack

Undergraduate Honors Capstone Projects

Mycoplasmas and mycobacteria are two types of opportunistic pathogens whose prevalence and virulence have long been underestimated. As a broad overview, this paper will explore the current understanding of these bacteria as well as some common pathological outcomes they can induce. Chronic infections, such as contagious bovine pleuropneumonia and Johne's disease, can have extensive health and economic impacts on animal industries when improperly managed. Contamination of biopharmaceuticals and human variants of disease, are also matters of concern as more research is conducted in these areas. A more detailed understanding of these bacteria is beginning to emerge-a view which reveals mycoplasmas …

Persecuting Alex Rodriguez: Race, Money And The Ethics Of Reporting The Performance-Enhancing Drug Scandal, Bonnie Brennen, Rick Brown

College of Communication Faculty Research and Publications

This qualitative textual analysis considers the US press coverage of Alex Rodriguez for his alleged use of performance-enhancing drugs. It evaluates nearly 500 newspaper, magazine and broadcast reports from 2007 to 2014 on Rodriguez, as well as reader and journalistic responses, and finds issues of overt and inferential racism, stereotyping and symbolic impurity, and a crude emphasis on money in the coverage. This research considers the ethics of the press coverage through a framework of Critical Race Theory and suggests an approach rooted in communitarian ethics to foster greater social justice and balance in sports media coverage.

Azolylimidazoles: Synthetic Strategies And Medicinal Applications, Bakr Fathy Abdelwahab, Rizk Elsayed Khidre

Turkish Journal of Chemistry

The current review summarizes the known routes to different azoles linked directly to imidazole. This review is divided into classes based on the type of azoles connected to an imidazole ring. Some medical applications are mentioned.

Speciation Of Chromium By The Combination Of Dispersive Liquid--Liquid Microextraction And Microsample Injection Flame Atomic Absorption Spectrometry, Yunusemre Ünsal, Mustafa Tüzen, Mustafa Soylak

Turkish Journal of Chemistry

A microextraction procedure was established for the speciation of total Cr, Cr(III), and Cr(VI). Sudan blue II was used as a ligand for speciation works. Some factors affecting the recoveries of chromium species, including type of extraction and dispersive solvents, pH, ligand amount, extraction time, and matrix ions, were examined. Optimum values for the dispersive liquid--liquid microextraction method were pH 6, LOD 0.34 \mu g L^{-1}, and preconcentration factor 400. Chromium(III) was quantitatively recovered under optimal conditions, while the recovery of chromium(VI) was below 10%. The relative standard deviation for Cr(III) determinations for the 10-replicate measurement of 0.3 \mu g …

Synthesis, Biological Evaluation, And Molecular Docking Of N'-(Aryl/Alkylsulfonyl)-1-(Phenylsulfonyl) Piperidine-4-Carbohydrazide Derivatives, Hira Khalid, Aziz Ur Rehman, Muhammad Athar Abbasi, Rashad Hussain, Khalid Mohammad Khan, Muhammad Ashraf, Syeda Abida Ejaz, Muhammad Qaiser Fatmi

Turkish Journal of Chemistry

A series of new N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazide derivatives were synthesized. Starting from ethyl piperidine-4-carboxylate (a), first ethyl 1-(phenylsulfonyl)piperidine-4-carboxylate (1), second 1-(phenylsulfonyl)piperidine-4-carbohydrazide (2), and finally N'-[(alkyl/aryl)sulfonyl]-1-(phenylsulfonyl)piperidine-4-carbohydrazides (4a--n) were synthesized by reacting 2 with alkyl/aryl sulfonyl chlorides (3a--n). The structures of the synthesized compounds were characterized by IR, ^1H-NMR, and EI-MS spectra and all were screened in vitro for their acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzyme inhibition activities. Molecular docking was accomplished for these compounds to examine their binding interactions with AChE and BChE human proteins. The strategy we applied for this purpose was a direct receptor-based approach. The binding modes of the inhibitors …

Fluorescence Quenching Study Of Moxifloxacin Interaction With Calf Thymus Dna, Yunkai Lv, Pan Li, Miao-Lun Jiao, Bao-Sheng Liu, Chao Yang

Turkish Journal of Chemistry

Moxifloxacin (MOX) is a fourth-generation synthetic fluoroquinolone antibacterial agent with many important therapeutic properties. Fluorescence quenching was used to study the interaction of MOX with calf thymus DNA (ct-DNA) in aqueous solution. The intercalative binding mode and a static quenching mechanism were confirmed by the Stern--Volmer quenching rate constant (K_q) of 3.48 \times 10^{11} M^{-1} s^{-1} at 298 K. The thermodynamic parameters (\Delta H = --118.4 KJ mol^{-1} and \Delta S = --299.4 J mol^{-1} K^{-1}) were calculated at different temperatures, and they indicate that the main forces between MOX and ct-DNA are hydrogen bonding and Van der Waals force. …

Spectrophotometric Determination Of Molybdenum Using Surfactant-Mediated Liquid--Liquid Extraction, Rameshwar Dass, Jitander Kumar Kapoor, Sunita Gambhir

Turkish Journal of Chemistry

A new spectrophotometric method has been developed for determination of molybdenum using surfactant-mediated liquid--liquid extraction. Molybdenum(V) obtained by ascorbic acid reduction in 2.5 M H_2SO_4 reacted spontaneously with thiocyanate and cetyl trimethyl ammonium bromide (CTAB), forming an intense orange yellow complex that was extracted quantitatively into 1,2-dichloroethane and absorbed at 460 nm. The absorbance of the extract was found to be stable for more than 24 h. Beer's law was obeyed over the concentration range 0.1--4.2 \mu g Mo mL^{-1} of the extract. The linear range for an accurate determination was found to be 1.2--2.6 \mu g Mo mL^{-1}. The …

In Vitro Effects Of Pesticide Exposure On The Activity Of The Paraoxonase-1 Enzyme From Sheep Liver Microsomes, Büşra Cebeci̇, Zuhal Alim, Şükrü Beydemi̇r

Turkish Journal of Chemistry

The organophosphate target enzyme paraoxonase-1 (PON1) has been extensively studied in toxicology. Pesticides are organophosphate compounds that are commonly used in agriculture. They are also used as nerve gases, such as sarin and soman. Therefore, the effects of these compounds on enzymatic activity are well known. In the present study, we investigated the in vitro effects of fenoxaprop-p-ethyl, lambda cyhalothrin, imidacloprid, and dichlorvos pesticides on sheep liver microsomal PON1. The enzyme was purified approximately 141-fold with a specific activity of 1822.22 EU/mg proteins. The pesticides inhibited sheep liver PON1 in vitro, and the IC_{50} values for these compounds were 0.0103, …

Partial Purification And Biochemical Characterization Of An Extremely Thermo- And Ph-Stable Esterase With Great Substrate Affinity, Esra Özbek, Yakup Kolcuoğlu, Leyla Konak, Ahmet Çolak, Fulya Öz

Turkish Journal of Chemistry

An esterase from a thermophilic bacterium, Geobacillus sp. DF20, was partially purified. Final purification factor was found to be 64.5-fold using Q-Sepharose ion exchange column chromatography. Native polyacrylamide gel electrophoresis indicated the presence of a single active esterase. The substrate specificity of this esterase was high for p-nitrophenyl butyrate (pNPB) substrate. The optimum pH and temperature for the enzyme activity were 7.0 and 50 ^°C, respectively. The pH and heat stability profiles show that this enzyme is more stable under neutral conditions at 50 ^°C. K_m and V_{max} values for this esterase acting on pNPB were 0.12 mM and 54.6 …

Antioxidant, Anticholinesterase, And Antimicrobial Activities And Fatty Acid Constituents Of Achillea Cappadocica Hausskn. Et Bornm., Abdulselam Ertaş, Mehmet Boğa, Nesri̇n Haşi̇mi̇, Yeter Yeşi̇l, Ahmet Ceyhan Gören, Gülaçti Topçu, Ufuk Kolak

Turkish Journal of Chemistry

This study was the first fatty acid analysis and biological activity report on an endemic Achillea species, Achillea cappadocica Hausskn. et Bornm. The major compounds in the fatty acid were identified as oleic (34.7 %), palmitic (23.1 %), and linoleic acids (20.6 %). The methanol and water extracts indicated higher ABTS cation radical scavenging activity than that of \alpha-tocopherol and BHT at 100 \mu g/mL. The acetone extract showed 70.62 % inhibitory activity against butyrylcholinesterase at 200 \mu g/mL. The acetone and methanol extracts exhibited moderate antimicrobial activity.

Convenient Synthesis Of New Polysubstituted Isoindole-1,3-Dione Analogues, Ayşe Tan, Mustafa Zahri̇tti̇n Kazancioğlu, Derya Aktaş, Özlem Gündoğdu, Ertan Şahi̇n, Nurhan Ki̇shali, Yunus Kara

Turkish Journal of Chemistry

Three new polysubstituted isoindole-1,3-diones were prepared from 2-ethyl-5-hydroxy-3a,4,5,7a-tetrahydro-isoindole-1,3-dione. The reaction of 2-ethyl-5-hydroxy-3a,4,5,7a-tetrahydro-isoindole-1,3-dione with m-CPBA gave the corresponding epoxide. The triacetate derivative was obtained via cis-hydroxylation using OsO_4, followed by acetylation. An aromatic derivative, a secondary reaction product, was also formed during the acetylation. Finally, a tricyclic derivative from 2-ethyl-5-hydroxy-3a,4,5,7a-tetrahydro-isoindole-1,3-dione was synthesized via dichloroketene addition under microwave irradiation. The exact structures of epoxide and tricyclic derivatives were determined by X-ray diffraction analysis.

Rosmarinic Acid: A Potent Carbonic Anhydrase Isoenzymes Inhibitor, Meryem Topal, İlhami̇ Gülçi̇n

Turkish Journal of Chemistry

Rosmarinic acid is a water-soluble ester of caffeic acid and 3,4-dihydroxyphenyllactic acids, and is mainly found in plant species including Boraginaceae and Lamiaceae. In this research, we determined the inhibition property of rosmarinic acid on carbonic anhydrase isoenzymes I and II (hCA I and II) purified from human erythrocytes by using Sepharose-4B affinity column chromatography. hCA I and II isoenzymes were obtained with a yield of 57.9% and 67.2% and 76.5- and 509.3-fold purification of each isoenzyme, respectively. In order to show the purity of the isoenzymes, SDS-PAGE was performed and one band was observed. In vitro inhibition of both …

Boron-Containing Tetrapyrroles, Şennur Özçeli̇k, Ahmet Gül

Turkish Journal of Chemistry

The recent advances in the synthesis of carborane and boronic ester-substituted tetrapyrroles (porphyrins, porphyrazines, and phthalocyanines) are reviewed together with their possible utilization as agents for photodynamic therapy (PDT) and boron neutron capture therapy of cancer (BNCT) as well as dual PDT/BNCT sensitizers.

Did Schelling Misunderstand Fichte’S Transcendental Method?, Michael Vater

Philosophy Faculty Research and Publications

The Fichte-Schelling Correspondence interweaves intriguing personal stories and philosophical combat. One of the sadder personal stories involves Schelling getting wind of Fichte’s remark to Friedrich Schlegel that he did not understand transcendental method. The letters document several clumsy attempts by Fichte to minimize the criticism only to have it surface again in a letter Fichte wrote to a former student, Jean Baptiste Schad, who showed the letter to Schelling. In it, Fichte claimed that Schelling understood Wissenschaftslehre no better than Friedrich Nicolai, whom Fichte had publicly excoriated for critiquing as “I-philosophy” a superficial assemblage of random quotes from mixed sources.

Urban Ecology: Advancing Science And Society, Colby J. Tanner, Frederick R. Adler, Nancy B. Grimm, Peter M. Groffman, Simon A. Levin, Jason Munshi-South, Diane E. Pataki, Mitchell Pavao-Zuckerman, William G. Wilson

School of Biological Sciences: Faculty Publications

Urban ecology has quickly become established as a central part of ecological thinking. As cities continue to grow in size and number, two questions serve to unify this broad and multidisciplinary research landscape: (1) how can urban ecology contribute to the science of ecology, and (2) how can urban ecology be applied to make cities more livable and sustainable? In spite of the advances made thus far, there are many unexplored ways of integrating the science and application of urban ecology. Although scientists assess and make predictions regarding the connections between environmental and socioeconomic processes, practitioners involved in real-world application …

Individual Phenotypic Variation Reduces Interaction Strengths In A Consumer–Resource System, Jean P. Gibert, Chad Brassil

School of Biological Sciences: Faculty Publications

Natural populations often show variation in traits that can affect the strength of interspecific interactions. Interaction strengths in turn influence the fate of pairwise interacting populations and the stability of food webs. Understanding the mechanisms relating individual phenotypic variation to interaction strengths is thus central to assess how trait variation affects population and community dynamics. We incorporated nonheritable variation in attack rates and handling times into a classical consumer–resource model to investigate how variation may alter interaction strengths, population dynamics, species persistence, and invasiveness. We found that individual variation influences species persistence through its effect on interaction strengths. In many …

Comparison Of The Wing Polyphenic Response Of Pea Aphids (Acyrthosiphon Pisum) To Crowding And Predator Cues, Swapna R. Purandare, Brigitte Tenhumberg, Jennifer A. Brisson

School of Biological Sciences: Faculty Publications

1. Pea aphids (Acyrthosiphon pisum Harris; Hemiptera: Aphididae) exhibit transgenerational wing polyphenism, in which unwinged females produce genetically identical winged offspring in response to environmental cues such as overcrowding and predation risk that indicate poor habitat quality.

2. Laboratory experiments were carried out to explore the intensity of the wing polyphenic response of pea aphids exposed to cues from ladybird predators and crowding, and their response was compared to pea aphids that were not exposed to any cues (control).

3. The study used cues from two different ladybird species: Coccinella septempunctata L. (Coleoptera: Coccinellidae) and Hippodamia convergens Guérin-Méneville (Coleoptera: …

Different Gene-Specific Mechanisms Determine The ‘Revised-Response’ Memory Transcription Patterns Of A Subset Of A. Thaliana Dehydration Stress Responding Genes, Ning Liu, Yong Ding, Michael Fromm, Zoya Avramova

School of Biological Sciences: Faculty Publications

Plants that have experienced several exposures to

dehydration stress show increased resistance to future

exposures by producing faster and/or stronger

reactions, while many dehydration stress responding

genes in Arabidopsis thaliana super-induce their

transcription as a ‘memory’ from the previous encounter.

A previously unknown, rather unusual,

memory response pattern is displayed by a subset

of the dehydration stress response genes. Despite

robustly responding to a first stress, these genes

return to their initial, pre-stressed, transcript levels

during the watered recovery; surprisingly, they do

not respond further to subsequent stresses of similar

magnitude and duration. This transcriptional behavior

defines the …

H3k27me3 And H3k4me3 Chromatin Environment At Super-Induced Dehydration Stress Memory Genes Of Arabidopsis Thaliana, Ning Liu, Zoya Avramova, Michael Fromm

School of Biological Sciences: Faculty Publications

Pre-exposure to a stress may alter the plant’s cellular, biochemical, and/or transcriptional responses during future encounters as a “memory” from the previous stress. Genes increasing transcription in response to a first dehydration stress, but producing much higher transcript levels in a subsequent stress, represent the super-induced “transcription memory” genes in Arabidopsis thaliana. The chromatin environment (histone H3 tri-methylations of Lys 4 and Lys 27, H3K4me3, and H3K27me3) studied at five dehydration stress memory genes revealed existence of distinct memory-response subclasses that responded differently to CLF deficiency and displayed different transcriptional activities during the watered recovery periods. Among the most …

Nocturnal Homing In The Tropical Amblypygid Phrynus Pseudoparvulus (Class Arachnida, Order Amblypygi), Eileen Hebets, E.J. Gering, Verner P. Bingman, Daniel D. Wiegmann

Eileen Hebets Publications

Arthropods are renowned for their navigational capabilities, with numerous examples known from insects and crustaceans. Early studies of amblypygids (Class Arachnida, Order Amblypygi) also suggest complex nocturnal navigation, despite their apparent lack of visual adaptations to the low-light conditions of a tropical understory. In a series of two studies, we use the tropical amblypygid, Phrynus pseudoparvulus, to assess their nocturnal homing ability. Our first experiment displaced and tracked resident and nonresident individuals. Resident individuals, displaced up to 4.5 m from their home refuges and released onto their home tree, were more likely to return to their previously occupied refuge than …

Arabidopsis Cuticular Wax Biosynthesis Is Negatively Regulated By The Dewax Gene Encoding An Ap2/Erf-Type Transcription Factor, Young Sam Go, Hyojin Kim, Hae Jin Kim, Mi Chung Suh

Department of Biochemistry: Faculty Publications

The aerial parts of plants are protected from desiccation and other stress by surface cuticular waxes. The total cuticular wax loads and the expression of wax biosynthetic genes are significantly downregulated in Arabidopsis thaliana under dark conditions. We isolated Decrease Wax Biosynthesis (DEWAX), which encodes an AP2/ERF-type transcription factor that is preferentially expressed in the epidermis and induced by darkness. Disruption of DEWAX leads to an increase in total leaf and stem wax loads, and the excess wax phenotype of dewax was restored to wild type levels in complementation lines. Moreover, overexpression of DEWAX resulted in a reduction …

Plant Acyl-Coa:Lysophosphatidylcholine Acyltransferases (Lpcats) Have Different Specificities In Their Forward And Reverse Reactions, Ida Lager, Jenny Lindberg Yilmaz, Xue-Rong Zhou, Katarzyna Jasieniecka, Michael Kazachkov, Peng Wang, Jitao Zou, Randall Weselake, Mark A. Smith, Shen Bayon, John M. Dyer, Jay Shockey, Ernst Heinz, Allan Green, Antoni Banas, Sten Stymne

Department of Biochemistry: Faculty Publications

Background: Acyl-CoA:lysophosphatidylcholine acyltransferase (LPCAT) enzymes have central roles in acyl editing of phosphatidylcholine.

Results: Plant LPCATs were expressed in yeast and biochemically characterized.

Conclusion: LPCATs can edit acyl composition of phosphatidylcholine through their combined forward and reverse reactions.

Significance: Plant LPCATs play a role in editing both sn-positions of PC and remove ricinoleic acid with high selectivity from this lipid.

Emerging Regulatory Paradigms In Glutathione Metabolism, Yilin Liu, Annastasia S. Hyde, Melanie A. Simpson, Joseph J. Barycki

Department of Biochemistry: Faculty Publications

One of the hallmarks of cancer is the ability to generate and withstand unusual levels of oxidative stress. In part, this property of tumor cells is conferred by elevation of the cellular redox buffer glutathione. Though enzymes of the glutathione synthesis and salvage pathways have been characterized for several decades, we still lack a comprehensive understanding of their independent and coordinate regulatory mechanisms. Recent studies have further revealed that overall central metabolic pathways are frequently altered in various tumor types, resulting in significant increases in biosynthetic capacity, and feeding into glutathione synthesis. In this review, we will discuss the enzymes …

Emerging Roles For Hyaluronidase In Cancer Metastasis And Therapy, Caitlin O. Mcatee, Joseph J. Barycki, Melanie A. Simpson

Department of Biochemistry: Faculty Publications

Hyaluronidases are a family of five human enzymes that have been differentially implicated in the progression of many solid tumor types, both clinically and in functional studies. Advances in the past five years have clarified many apparent contradictions, (1) by demonstrating that specific hyaluronidases have alternative substrates to hyaluronan (HA) or do not exhibit any enzymatic activity, (2) that high molecular weight HA polymers elicit signaling effects that are opposite those of the hyaluronidase-digested HA oligomers, and (3) that it is actually the combined overexpression of HA synthesizing enzymes with hyaluronidases that confers tumorigenic potential. This review examines the literature …

Homogeneous Low-Molecular-Weight Heparins With Reversible Anticoagulant Activity, Yongmei Xu, Chao Cai, Kasemsiri Chandarajoti, Po-Hung Hsieh, Lingyun Li, Truong Q. Pham, Erica M. Sparkenbaugh, Juzheng Sheng, Nigel S. Key, Rafal Pawlinski, Edward N. Harris, Robert J. Linhardt, Jian Liu

Department of Biochemistry: Faculty Publications

Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs.

Immunity Ratione Personae Of Foreign Government Officials And Other Topics: The Sixty-Fifth Session Of The International Law Commission, Sean D. Murphy

GW Law Faculty Publications & Other Works

The International Law Commission held its sixty-fifth session in Geneva from May 6 to June 7 and from July 8 to August 9, 2013. The Commission devoted most of the sixty-fifth session to discussing three topics: immunity of state officials from foreign criminal jurisdiction; subsequent agreements and subsequent practice in relation to the interpretation of treaties; and protection of persons in the event of disasters. Notably, the Commission adopted three draft articles and commentary identifying three senior governmental officials as entitled to immunity ratione personae from foreign criminal jurisdiction – heads of state, heads of government, and foreign ministers – …

Hepatoprotective Role Of Sestrin2 Against Chronic Er Stress, Hwan-Woo Park, Haeli Park, Seung-Hyun Ro, Insook Jang, Ian A. Semple, David N. Kim, Myungjin Kim, Myeongjin Nam, Deqiang Zhang, Lei Yin, Jun Hee Lee

Department of Biochemistry: Faculty Publications

Upon prolonged endoplasmic reticulum (ER) stress, cells attenuate protein translation to prevent accumulation of unfolded proteins. Here we show that Sestrin2 is critical for this process. Sestrin2 expression is induced by an ER stress-activated transcription factor CCAATenhancer- binding protein beta (c/EBPβ). Once induced, Sestrin2 halts protein synthesis by inhibiting mammalian target of rapamycin complex 1 (mTORC1). As Sestrin2-deficient cells continue to translate a large amount of proteins during ER stress, they are highly susceptible to ER stress-associated cell death. Accordingly, dietary or genetically induced obesity, which does not lead to any pathological indication other than simple fat accumulation in the …

Pharmacological Correction Of Obesity-Induced Autophagy Arrest Using Calcium Channel Blockers, Hwan-Woo Park, Haeli Park, Ian A. Semple, Insook Jang, Seung-Hyun Ro, Myungjin Kim, Victor A. Cazares, Edward L. Stuenkel, Jung-Jae Kim, Jeong Sig Kim, Jun Hee Lee

Department of Biochemistry: Faculty Publications

Autophagy deregulation during obesity contributes to the pathogenesis of diverse metabolic disorders. However, without understanding the molecular mechanism of obesity interference in autophagy, development of therapeutic strategies for correcting such defects in obese individuals is challenging. Here we show that a chronic increase of the cytosolic calcium concentration in hepatocytes during obesity and lipotoxicity attenuates autophagic flux by preventing the fusion between autophagosomes and lysosomes. As a pharmacological approach to restore cytosolic calcium homeostasis in vivo, we administered the clinically approved calcium channel blocker verapamil to obese mice. Such treatment successfully increases autophagosome–lysosome fusion in liver, preventing accumulation of …