Chemical and Pharmacologic Phenomena Commons^™

Dna Aptamer-Drug Targeting Chemotherapy: Investigation Of Cell Cycle Inhibition Via S15 Aptamer – Norcantharidin Complex, Shannon Fehr

Senior Honors Theses

Lung Cancer is the leading cause of cancer related death in both men and women in the United States (Bray et al., 2018). Cancer treatments are often non-specific and kill many dividing cells within a patient causing unwanted side effects. Norcantharidin (NCTD) is a synthetic FDA approved treatment for cancers including non-small cell lung cancers (NSCLC). NCTD suppresses cell proliferation by inhibiting cells from exiting the G2 phase of the cell cycle. Aptamers are short single-stranded DNA or RNA molecules with ligand directed self-annealing capabilities allowing selective binding to specific targets. This paper will discuss the hypothesized effects of using …

Veru-111 As An Oral Tubulin Inhibitor Suppressing Triple-Negative Breast Cancer And Evaluation Of Novel Tubulin Inhibitors For Cancer Therapy, Shanshan Deng

Theses and Dissertations (ETD)

Triple negative breast cancer (TNBC) has aggressive clinical features strongly associated with poorer overall prognosis and higher mortality rates relative to other molecular subtypes. FDA-approved drugs, such as paclitaxel, are effective in treating TNBC. Yet, treatment failure is commonly observed due to the development of acquired chemoresistance, which remains a clinical challenge for TNBC therapy.

Vitamin D Levels Affect Survival In A Bcr-Abl Acute Lymphoblastic Leukemia Mouse Model But Do Not Cause Vitamin-Drug Interactions, Kavya Annu

Theses and Dissertations (ETD)

It is a well-established phenomenon that dietary components containing CYP3A inducers or inhibitors if co-administered with drugs that are CYP3A4 substrates lead to marked drug-drug interactions. Because vitamin D is known to regulate intestinal CYP3A expression and gut CYP3A expression plays an important role in pre-systemic metabolism of CYP3A drugs, we determined the impact of vitamin D (VD3) status on systemic exposure and efficacy of chemotherapeutic agents that are CYP3A substrates. We employed VD3 sufficient and deficient mice to perform pharmacokinetics (PK) and anti-leukemic efficacy studies.

First, using hCYP3A4 transgenic mouse model we evaluated the intestinal, hepatic and renal expression …

Study On The Formulation And Characterization Of A Photoprotective Cream Containing A New Synthetized Compound, Teodora Dalila Balaci, Emma Adriana Ozon, Daniela Luiza Baconi, Georgiana Nițulescu, Bruno Velescu, Cristian Bălălău, Ioana Păunică, Cătălina Ancuța Fița

Journal of Mind and Medical Sciences

Starting from a new organic sunscreen synthesized in our laboratory by the condensation of sodium salt of the p-aminosalicylic acid with 2,6 – dichloroacetanilide, efficient cosmetic formulation with broad photoprotective properties was obtained by using the new compound as organic UV filter, metal oxides as inorganic filters, and vegetable extracts, oils and other ingredients with emollient, protective, and moisturizing effect. After showing the lack of toxicity of the new compound, in order to reduce the amount of UV filter used, it was encapsulated into nanostructured lipid carriers (NLCs). The final cream has demonstrated good qualities for skin application, possessing suitable …

Oral Pathology Induced By Excess Or Deficiency Of Glucocorticoids In Adults, Rucsandra Elena Dănciulescu Miulescu, Loreta Guja, Bogdan Socea, Anca Dumitriu, Stana Paunica, Emil Ștefănescu

Journal of Mind and Medical Sciences

Oral manifestations are present both in Cushing's syndrome and in adrenal insufficiency. Possible oro-dental pathology in patients with Cushing's syndrome include jawbone loss, tooth loss, and periodontal diseases. Professional societies did not include Cushing's syndrome as being part of systemic diseases associated with loss of periodontal supporting tissues. The comorbidities of Cushing's syndrome such as obesity, osteoporosis, and diabetes are conditions that influence periodontal attachment apparatus. In patients with adrenal primary insufficiency, the most specific sign is the melanic pigmentation of the skin and mucosal surfaces due to increments of corticotropin and pro-opiomelanocortin peptide levels that occur as a result …

Capsaicin Is A Negative Allosteric Modulator Of The 5-Ht3 Receptor, Eslam El Nebrisi, Tatiana Prytkova, Dietrich Ernst Lorke, Luke Howarth, Asma Hassan Alzaabi, Keun-Hang Susan Yang, Frank Christopher Howarth, Murat Oz

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

In this study, effects of capsaicin, an active ingredient of the capsicum plant, were investigated on human 5-hydroxytryptamine type 3 (5-HT₃) receptors. Capsaicin reversibly inhibited serotonin (5-HT)-induced currents recorded by two-electrode voltage clamp method in Xenopus oocytes. The inhibition was time- and concentration-dependent with an IC₅₀ = 62 μM. The effect of capsaicin was not altered in the presence of capsazepine, and by intracellular BAPTA injections or trans-membrane potential changes. In radio-ligand binding studies, capsaicin did not change the specific binding of the 5-HT₃ antagonist [³H]GR65630, indicating that it is a noncompetitive inhibitor of …

Opioid Dependency And Its Effects On Alcohol Consumption, Emily V. Flores

Psychology and Counseling Theses

Previous research has found dualistic effects on alcohol consumption with low doses of buprenorphine increasing alcohol and higher doses of buprenorphine reducing alcohol consumption in rats (Ciccocioppo et al., 2006). Other existing research on naloxone treatment and alcohol consumption in opioid use has demonstrated that alcohol consumption decreases after naloxone treatment in rats (Hyytia & Sinclair, 1993). Yet, no research has been conducted on either rats or humans on the effects of buprenorphine and naloxone medication combined. The effects of opioid maintenance therapy are controversial and the relationship between alcohol consumption and opioid dependency treatment is mainly based on literature …

Cyclic Peptide-Gadolinium Nanoparticles For Enhanced Intracellular Delivery, Amir Nasrolahi Shirazi, Shang Eun Park, Shirin Rad, Luiza Baloyan, Dindyal Mandal, Muhammad Imran Sajid, Ryley Hall, Sandeep Lohan, Khalid Zoghebi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

A cyclic peptide containing one cysteine and five alternating tryptophan and arginine amino acids [(WR)₅C] was synthesized using Fmoc/tBu solid-phase methodology. The ability of the synthesized cyclic peptide to produce gadolinium nanoparticles through an in situ one-pot mixing of an aqueous solution of GdCl₃ with [(WR)₅C] peptide solution was evaluated. Transmission electron microscopy showed the formed peptide-Gd nanoparticles in star-shape morphology with a size of ~250 nm. Flow cytometry investigation showed that the cellular uptake of a cell-impermeable fluorescence-labeled phosphopeptide (F′-GpYEEI, where F′ = fluorescein) was approximately six times higher in the presence of [(WR) …

Directed Evolution Of Macrocyclic Peptides For Inhibition Of Autophagy, Joshua Gray

Dissertations and Theses (Open Access)

In recent decades it has become increasingly clear that induction of autophagy plays an important role in the development of treatment resistance and dormancy in many cancer types. Chloroquine (CQ) and hydroxychloroquine (HCQ), two autophagy inhibitors in clinical trials, suffer from poor pharmacokinetics and high toxicity at therapeutic dosages. This has prompted intense interest in the development of targeted autophagy inhibitors to re-sensitize disease to treatment with minimal impact on normal tissue. We utilized Scanning Unnatural Protease Resistant (SUPR) mRNA display to develop macrocyclic peptides targeting the autophagy protein LC3. The resulting peptides bound LC3A and LC3B—two essential components of …

Malignant Hyperthermia For The Nurse Anesthetist, Victor Clark

Nursing Student Class Projects (Formerly MSN)

Malignant Hyperthermia (MH) is a rare, autosomal dominant skeletal muscle disorder that can have an insidious onset in susceptible patients exposed to the triggering agents succinylcholine, halothane, desflurane, sevoflurane, and isoflurane. MH can occur in patients who have received anesthesia with these agents in the past (Nagelhout & Plaus, 2018, p 775). Patients with a family history of MH or associated skeletal muscle disorder must be treated as MH-susceptible until proven otherwise. Failure to detect an MH crisis can lead to kidney failure, profound acidosis, coagulopathies, rhabdomyolysis, cardiac dysrhythmias, cardiovascular collapse, and death (Seifert et al., 2015). It is the …

Role Of Neuronal Nitric Oxide Synthase On Cardiovascular Functions In Physiological And Pathophysiological States, Ahmmed Ally, Isabella Powell, Minora M. Ally, Kevin Chaitoff, Surya M. Nauli

Pharmacy Faculty Articles and Research

This review describes and summarizes the role of neuronal nitric oxide synthase (nNOS) on the central nervous system, particularly on brain regions such as the ventrolateral medulla (VLM) and the periaqueductal gray matter (PAG), and on blood vessels and the heart that are involved in the regulation and control of the cardiovascular system (CVS). Furthermore, we shall also review the functional aspects of nNOS during several physiological, pathophysiological, and clinical conditions such as exercise, pain, cerebral vascular accidents or stroke and hypertension. For example, during stroke, a cascade of molecular, neurochemical, and cellular changes occur that affect the nervous system …

Comparative Molecular Transporter Properties Of Cyclic Peptides Containing Tryptophan And Arginine Residues Formed Through Disulfide Cyclization, Eman H. M. Mohammed, Dindyal Mandal, Saghar Mozaffari, Magdy Abdel-Hamied Zahran, Amany Mostafa Osman, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

We have previously reported cyclic cell-penetrating peptides [WR]₅ and [WR]₄ as molecular transporters. To optimize further the utility of our developed peptides for targeted therapy in cancer cells using the redox condition, we designed a new generation of peptides and evaluated their cytotoxicity as well as uptake behavior against different cancer cell lines. Thus, cyclic [C(WR)_xC] and linear counterparts (C(WR)_xC), where x = 4–5, were synthesized using Fmoc/tBu solid-phase peptide synthesis, purified, and characterized. The compounds did not show any significant cytotoxicity (at 25 µM) against ovarian (SK-OV-3), leukemia (CCRF-CEM), gastric adenocarcinoma (CRL-1739), breast …

Modulator Therapy For Cystic Fibrosis: An Exploration Of Current Research, Jessalyn Rombocos

Senior Honors Theses

Developing a drug therapy that addresses the root cause of cystic fibrosis (CF) by increasing CFTR protein levels has long been a research challenge. After genetic therapy failed because a suitable delivery system could not be found, researchers began searching for small organic molecules that could act as chaperones for CFTR. These molecules, known as modulators, allowed CFTR to be assembled correctly and function similarly to wild type CFTR. Since 2012, four modulator drugs have been developed, tested, and approved by the FDA. In October 2019, Trikafta was approved as the first triple-combination modulator drug and has completely revolutionized CF …

Elucidation Of The Mechanisms By Which Anesthetics Induce Blood-Brain Barrier Breakdown And Delirium In The Elderly, George A. Godsey Ii

Graduate School of Biomedical Sciences Theses and Dissertations

Delirium is a highly prevalent neuropsychiatric or neurocognitive disorder that presents a major problem to modern healthcare. Patients suffering from delirium normally have a worse prognosis, prolonged hospital stay, increased hospital cost, long-term cognitive impairment, and higher mortality rates. Many factors can predispose one to develop delirium, which makes treating this disorder a daunting task. Unfortunately, delirium is the most common psychiatric syndrome found in the hospital setting. In fact, a form of delirium known as postoperative delirium (POD) is one of the most common postoperative complications faced by elderly patients undergoing surgery.

POD is a major problem in modern …

Renal Safety And Racial Disparity In Patients On Antiviral Treatment For Chronic Hepatitis B, Matthew Miller, Sindhuri Benjaram, Raya Kutaimy, Paul Naylor, Elizabeth May, Murray Ehrinpreis, Milton Mutchnick

Medical Student Research Symposium

Background:

Many African Americans (AA) are chronically infected with Hepatitis B (HBV). While antiviral therapy is highly effective, clinical trials suggest a treatment-related decline in kidney function is possible. Given that chronic HBV predominately affects Asians worldwide, most studies have contained few AA patients. We evaluated these treatment-related kidney function changes in our predominately AA patient population.

Methods:

From 225 HBV patients, we identified 42 patients who were not co-infected with HIV or HCV, had a recent visit, and at least one earlier visit (before Jan 2017). If on treatment with antivirals it must have been for at least 2 …

A Chronic Strain Of The Cystic Fibrosis Pathogen Pandoraeapulmonicola Expresses A Heterogenous Hypo-Acylated Lipid A, Molly D. Pither, Siobhan Mcclean, Alba Silipo, Antonio Molinaro, Flaviana Di Lorenzo

Articles

Pandoraeasp. is an emerging Gram-negative pathogen in cystic fibrosis causing severe and persistent inflammation and damageof the lungs. The molecular mechanisms underlying the high pathogenicity ofPandoraeaspecies are still largely unknown. AsGram-negatives,Pandoraeasp. express lipopolysaccharides (LPS) whose recognition by the host immune system triggers aninflammatory response aimed at the bacterial eradication from the infected tissues. The degree of the inflammatory responsestrongly relies on the fine structure of the LPS and, in particular, of its glycolipid moiety, i.e. the lipid A. Here we report thestructure of the lipid A isolated from the LPS of a chronic strain ofP. pulmonicola(RL 8228), one of the …

A Short Remark On Multipurpose Laser Therapy “Helios” In Ukraine And Its Potential Application For Treatment Of Neurology Disorders, Florentin Smarandache, Volodymyr Krasnoholovets, Victor Christianto, Rizha Vitania, The Houw Liong

Branch Mathematics and Statistics Faculty and Staff Publications

However, a truly multipurpose laser therapy method is very rarely available. Here we introduce a multipurpose laser therapy device in Ukraine, which is capable to take care a multitude of diseases. It is called “Helios”, by one of us (VK). We also give a case where a patient who suffered from Covid-19 has been treated successfully until he is recovered to healthy condition. In the last section we also discuss potential future application of Helios for other fields; i.e. neurology disorders.

Correlating The Physicochemical Properties Of Magnesium Stearate With Tablet Dissolution And Lubrication, Julie L. Calahan

Theses and Dissertations--Pharmacy

Magnesium stearate (MgSt) is the most commonly used pharmaceutical excipient and is present in over half the tablet formulations on the market. In spite of its popularity as an effective lubricant, it has been repeatedly recognized that there is significant variability between MgSt samples, which can cause inconsistent lubrication between batches of MgSt. The hypothesis of this research is that the batch-to-batch variability in tablet lubrication and dissolution observed in tablet formulations containing different MgSt samples can be correlated with differences in MgSt physicochemical properties (fatty acid salt composition, crystal hydrate form, particle size and surface area). Developing correlations between …

Effects Of Topical Application Of Combined Phyllanthus Emblica Linn. And Simvastatin On Diabetic Wound In Mice, Tingting Liao

Chulalongkorn University Theses and Dissertations (Chula ETD)

Non-healing diabetic foot ulcers are the most common cause of lower extremity amputation. Drug combination treatment is the most recent emerging strategy in local treatment of diabetic wound. This study aimed to find out the combined effects and underlying mechanisms of combined Phyllanthus emblica Linn. (PE) and simvastatin (SIM) on diabetic wound in mice. Male BALB/C mice were divided into five groups: control group (CON+Vehicle), diabetic wounded group (DM+Vehicle, streptozotocin 45 mg/kg. i.p. daily for 5 days), diabetic wounded groups with daily treatment of 100%PE cream, 5%SIM cream, and 100%PE+5%SIM combined cream, w/v, for 4 days, 7 days and 14 …

Population Pharmacokinetics Of Intravenous Colistin In Pediatrics (Poppicop Study), Noppadol Wacharachaisurapol

Chulalongkorn University Theses and Dissertations (Chula ETD)

Background: Colistin use in pediatrics is surging in line with the increase of multidrug-resistant Gram-negative bacteria (MDR-GNB). However, the appropriate dose is uncertain owing to the lack of pharmacokinetics data. In this study, we aimed to characterize the pharmacokinetic parameters of colistin in pediatric patients, identify the factors influencing the pharmacokinetic parameters, and propose optimal dosage regimens. Methods: A prospective, multicenter, population pharmacokinetic (PPK) study was conducted. Serial blood samples were obtained from patients after receiving the standard colistin recommended dose of 5 mg of colistin base activity (CBA)/kg/day. Plasma colistin concentrations were measured. Data were pooled from this study …

Clincial Translational Science Research Of The Functional Role Of Large Conductance Potassium Channels In Selective Destruction Of Triple Negative Breast Cancer Cells, Gina Sizemore

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

The preliminary background that puts this research into context is threefold; it is the aggressive nature of triple negative breast cancer (TNBC), the complexity surrounding its pathology, and the significant lack of targeted treatment for this disease. To clarify the focus of my research, I have concentrated on identifying a targeted treatment for TNBC. In the process, I have identified cycles of reciprocity between treatment, clinical diagnosis, staging, and pathology that will be addressed in smaller papers. However, the weight of this work is in the discovery of a novel target for triple negative breast cancer. The value of …

Tripping Over The Other: Could Psychedelics Increase Empathy?, Emily Blatchford, Stephen Bright, Liam Engel

Research outputs 2014 to 2021

There is increasing evidence that psychedelic-assisted psychotherapy is effective for a range of psy-chological conditions. There are likely numerous mechanisms of action that contribute to these clinicaleffects. One such mechanism of action might involve psychedelics increasing levels of empathicfunctioning. This paper synthesises research concerning the relationship between psychedelics andempathy, emphasising neuroscientific and clinical contexts. We conclude that neuropsychological andclinical evidence imply psychedelics could lead to increased empathic functioning. The effects of psy-chedelics on the 5-HT system, default mode network, neural connectivity and ego dissolution areimplicated in these changes. Changes in empathic functioning also likely relate to increases in thepersonality trait …

Chemical Composition And Behavioural Responses Of Male And Female Bactrocera Dorsalis To Their Volatile Emissions, Fikira Kimbokota

Journal of Humanities and Social Sciences

Bactrocera dorsalis, (Tephritidae) presented a grave threat to a broad range of fruit and vegetables in the tropics, including Tanzania. Bactrocera dorsalis is among the most destructive tephritid fruit fly, causing devastating loss of fruits especially mango. Insects use olfactory cues to locate hosts, oviposition sites and mating, in which pheromones are believed to be a strong cue used by insect to locate their mates. However, due to their high ability to adapt and occupy different ecological niches into various agroecological zones, there is a need to evaluate pheromonal composition from time to time to improve their control strategies. Therefore, …

Residues And Residue Pairs Of Evolutionary Importance Differentially Direct Signaling Bias Of D2 Dopamine Receptors, María E Terrón-Díaz, Sara J Wright, Melina A Agosto, Olivier Lichtarge, Theodore G Wensel

Faculty, Staff and Students Publications

The D2 dopamine receptor and the serotonin 5-hydroxytryptamine 2A receptor (5-HT2A) are closely-related G-protein–coupled receptors (GPCRs) from the class A bioamine subfamily. Despite structural similarity, they respond to distinct ligands through distinct downstream pathways, whose dysregulation is linked to depression, bipolar disorder, addiction, and psychosis. They are important drug targets, and it is important to understand how their bias toward G-protein versus β-arrestin signaling pathways is regulated. Previously, evolution-based computational approaches, difference Evolutionary Trace and Evolutionary Trace–Mutual information (ET-Mip), revealed residues and residue pairs that, when switched in the D2 receptor to the corresponding residues from 5-HT2A, altered ligand potency …

Evaluation Of Tumor Necrosis Factor Alpha In Sleep-Deprived Menopausal- Induced Rats And The Impact On Bone Health, Nicole Ellsworth, Dwight Curry Iii, Cj Deleon, Frank Frisch

Student Scholar Symposium Abstracts and Posters

Post-menopausal osteoporosis as a consequence of estrogen depletion is a growing concern for women in the United States. As more women take on executive positions and experience sleep deprivation, there is the potential for up regulation of pro-inflammatory cytokines, such as tumor necrosis factor alpha. It follows that the homeostatic imbalance of osteoclastic and osteoblastic activity leads to a greater risk of disease. Bisphosphonates generally, and Zolendronate specifically works by decreasing the number of osteoclasts. This current study investigated the impact of Zolendronate on the concentrations of tumor necrosis factor alpha-type (TNFɑ) in 32 ovariectomized Wistar rats. Throughout a five …

A Systematic Comparison Of Lipopolymers For Sirna Delivery To Multiple Breast Cancer Cell Lines: In Vitro Studies, Hamidreza Montazeri Aliabadi, Remant Bahadur Kc, Emira Bousoik, Ashley Barbarino, Bindu Thapa, Melissa Coyle, Parvin Mahdipoor, Hasan Uludağ

Pharmacy Faculty Articles and Research

Small interfering RNA (siRNA) therapy is a promising approach for treatment of a wide range of cancers, including breast cancers that display variable phenotypic features. To explore the general utility of siRNA therapy to control aberrant expression of genes in breast cancer, we conducted a detailed analysis of siRNA delivery and silencing response in vitro in 6 separate breast cancer cell models (MDA-MB-231, MDA-MB-231-KRas-CRM, MCF-7, AU565, MDA-MB-435 and MDA-MB-468 cells). Using lipopolymers for siRNA complexation and delivery, we found a large variation in siRNA delivery efficiency depending on the specific lipopolymer used for siRNA complexation and delivery. Some lipopolymers were …

Andexanet Alfa Is An Effective Reversal Agent For Factor Xa Inhibitors In Patients That Develop Intracranial Hemorrhage, Joseph Friedli

Clinical Research in Practice: The Journal of Team Hippocrates

A critical appraisal and clinical application of Connolly SJ, Milling TJ, Eikelboom JW, et al. Andexanet alfa for acute major bleeding associated with factor Xa inhibitors. N Engl J Med. 2016;375(12):1131-1141. doi: 10.1056/NEJMoa1607887.

Nuclear Magnetic Resonance Solution Structure And Functional Behavior Of The Human Proton Channel, Monika Bayrhuber, Innokentiy Maslennikov, Witek Kwiatkowski, Alexander Sobol, Christoph Wierschem, Cédric Eichmann, Lukas Frey, Roland Riek

Pharmacy Faculty Articles and Research

The human voltage-gated proton channel [Hv1⁽¹⁾ or VSDO⁽²⁾] plays an important role in the human innate immune system. Its structure differs considerably from those of other cation channels. It is built solely of a voltage-sensing domain and thus lacks the central pore domain, which is essential for other cation channels. Here, we determined the solution structure of an N- and C-terminally truncated human Hv1 (Δ-Hv1) in the resting state by nuclear magnetic resonance (NMR) spectroscopy. Δ-Hv1 comprises the typical voltage-sensing antiparallel four-helix bundle (S1–S4) preceded by an amphipathic helix (S0). The solution structure corresponds to an intermediate …

Edb-Fn Targeted Peptide–Drug Conjugates For Use Against Prostate Cancer, Shang Eun Park, Kiumars Shamloo, Timothy A. Kristedja, Shaban Darwish, Marco Bisoffi, Keykavous Parang, Rakesh Tiwari

Pharmacy Faculty Articles and Research

Prostate cancer (PCa) is the most common malignancy in men and is the leading cause of cancer-related male mortality. A disulfide cyclic peptide ligand [CTVRTSADC] 1 has been previously found to target extra domain B of fibronectin (EDB-FN) in the extracellular matrix that can dierentiate aggressive PCa from benign prostatic hyperplasia. We synthesized and optimized the stability of ligand 1 by amide cyclization to obtain [KTVRTSADE] 8 using Fmoc/tBu solid-phase chemistry. Optimized targeting ligand 8 was found to be stable in phosphate buered saline (PBS, pH 6.5, 7.0, and 7.5) and under redox conditions, with a half-life longer than 8 …

Molecular Recognition Of M1-Linked Ubiquitin Chains By Native And Phosphorylated Uban Domains, Lina Herhaus, Henry Van Den Bedem, Sean Teng, Innokentiy Maslennikov, Soichi Wakatsuki, Ivan Dikic, Simin Rahighi

Pharmacy Faculty Articles and Research

Although the Ub-binding domain in ABIN proteins and NEMO (UBAN) is highly conserved, UBAN-containing proteins exhibit different Ub-binding properties, resulting in their diverse biological roles. Post-translational modifications further control UBAN domain specificity for poly-Ub chains. However, precisely, how the UBAN domain structurally confers such functional diversity remains poorly understood. Here we report crystal structures of ABIN-1 alone and in complex with one or two M1-linked di-Ub chains. ABIN-1 UBAN forms a homo-dimer that provides two symmetrical Ub-binding sites on either side of the coiled-coil structure. Moreover, crystal structures of ABIN1 UBAN in complex with di-Ub chains reveal a concentration-dependency of …