Medicine and Health Sciences Commons^™

Intrinsically Disordered Proteins And Their (Disordered) Proteomes In Neurodegenerative Disorders, Vladimir N. Uversky

Molecular Medicine Faculty Publications

No abstract provided.

Beyond The Excluded Volume Effects: Mechanistic Complexity Of The Crowded Milieu, Irina M. Kuznetsova, Boris Y. Zaslavsky, Leonid Breydo, Konstantin K. Turoverov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Macromolecular crowding is known to affect protein folding, binding of small molecules, interaction with nucleic acids, enzymatic activity, protein-protein interactions, and protein aggregation. Although for a long time it was believed that the major mechanism of the action of crowded environments on structure, folding, thermodynamics, and function of a protein can be described in terms of the excluded volume effects, it is getting clear now that other factors originating from the presence of high concentrations of “inert” macromolecules in crowded solution should definitely be taken into account to draw a more complete picture of a protein in a crowded milieu. …

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: Ii. Unfolding Of The Monomeric Forms, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

In a family of monomeric odorant-binding proteins (OBPs), bovine OBP (bOBP), that lacks conserved disulfide bond found in other OBPs, occupies unique niche because of its ability to form domain-swapped dimers. In this study, we analyzed conformational stabilities of the recombinant bOBP and its monomeric variants, the bOBP-Gly121+ mutant containing an additional glycine residue after the residue 121 of the bOBP, and the GCC-bOBP mutant obtained from the bOBP-Gly121+ form by introduction of the Trp64Cys/His155Cys double mutation to restore the canonical disulfide bond. We also analyzed the effect of the natural ligand binding on the conformational stabilities of these bOBP …

Intrinsically Disordered Caldesmon Binds Calmodulin Via The “Buttons On A String” Mechanism, Sergei E. Permyakov, Eugene A. Permyakov, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We show here that chicken gizzard caldesmon (CaD) and its C-terminal domain (residues 636–771, CaD136) are intrinsically disordered proteins. The computational and experimental analyses of the wild type CaD136 and series of its single tryptophan mutants (W674A, W707A, and W737A) and a double tryptophan mutant (W674A/W707A) suggested that although the interaction of CaD136 with calmodulin (CaM) can be driven by the non-specific electrostatic attraction between these oppositely charged molecules, the specificity of CaD136-CaM binding is likely to be determined by the specific packing of important CaD136 tryptophan residues at the CaD136-CaM interface. It is suggested that this interaction can be …

Fendiline Inhibits Proliferation And Invasion Of Pancreatic Cancer Cells By Interfering With Adam10 Activation And Β-Catenin Signaling, Neha Woods, Jose Trevino, Domenico Coppola, Srikumar Chellappan, Shengyu Yang, Jaya Padmanabhan

Molecular Medicine Faculty Publications

ADAM10 (A Disintegrin and Metalloprotease Domain 10) affects the pathophysiology of various cancers, and we had shown that inhibition of ADAM10 sensitizes pancreatic cancer cells to gemcitabine. ADAM10 is activated in response to calcium influx, and here we examined if calcium channel blockers (CCB) would impede ADAM10 activation and affect biology of pancreatic cancer cells. We find that the CCB, fendiline, significantly reduces proliferation, migration, invasion, and anchorage independent growth of pancreatic cancer cells. This was associated with ADAM10 inhibition and its localization at the actin-rich membrane protrusions. Further, fendiline-treated cells formed cadherin-catenin positive tight adherens junctions and elicited defective …

Structure And Stability Of Recombinant Bovine Odorant-Binding Protein: I. Design And Analysis Of Monomeric Mutants, Olga V. Stepanenko, Denis O. Roginskii, Olesya V. Stepanenko, Irina M. Kuznetsova, Vladimir N. Uversky, Konstantin K. Turoverov

Molecular Medicine Faculty Publications

Bovine odorant-binding protein (bOBP) differs from other lipocalins by lacking the conserved disulfide bond and being able to form the domain-swapped dimers. To identify structural features responsible for the formation of the bOBP unique dimeric structure and to understand the role of the domain swapping on maintaining the native structure of the protein, structural properties of the recombinant wild type bOBP and its mutant that cannot dimerize via the domain swapping were analyzed. We also looked at the effect of the disulfide bond by designing a monomeric bOBPs with restored disulfide bond which is conserved in other lipocalins. Finally, to …

Intrinsic Disorder In Biomarkers Of Insulin Resistance, Hypoadiponectinemia, And Endothelial Dysfunction Among The Type 2 Diabetic Patients, Osama H. Jiffri, Fadwa M. Al-Sharif, Essam H. Jiffri, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with the all-cause and cardiovascular mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by …

Intrinsic Disorder In Biomarkers Of Insulin Resistance, Hypoadiponectinemia, And Endothelial Dysfunction Among The Type 2 Diabetic Patients, Osama H. Jiffri, Fadwa M. Al-Sharif, Essam H. Jiffri, Vladimir N. Uversky

Molecular Medicine Faculty Publications

Type 2 diabetes mellitus (T2DM) is a chronic and progressive disease that is strongly associated with the all-cause and cardiovascular mortality. The present study aimed to analyze the abundance and functionality of intrinsically disordered regions in several biomarkers of insulin resistance, adiponectin, and endothelial dysfunction found in the T2DM patients. In fact, in comparison to controls, obese T2DM patients are known to have significantly higher levels of inter-cellular adhesion molecule (iCAM-1), vascular cell adhesion molecule (vCAM-1), and E-selectin, whereas their adiponectin levels are relatively low. Bioinformatics analysis revealed that these selected biomarkers (iCAM-1, vCAM-1, E-selectin, and adiponectin) are characterized by …

“In-Plant” Nmr: Analysis Of The Intact Plant Vesicularia Dubyana By High Resolution Nmr Spectroscopy, Viktor P. Kutyshenko, Peter Beskaravayny, Vladimir N. Uversky

Molecular Medicine Faculty Publications

We present here the concept of “in-plant” NMR and show that high-resolution NMR spectroscopy is suitable for the analysis of intact plants and can be used to follow the changes in the intraorganismal molecular composition over long time periods. The NMR-based analysis of the effect of different concentrations of heavy water on the aquatic plant Vesicularia dubyana revealed that due to the presence of specific adaptive mechanisms this plant can sustain the presence of up to 85% of D₂O. However, it dies in 100% heavy water.

Expression Of The Nkcc2a Cotransporter In Mouse Central Nervous System, Katherine E. Fahy, James B. Lucot, Hayo Castrop, Mauricio Di Fulvio

Celebration of Undergraduate & Graduate Research, Scholarship, and Creative Activities Materials

Na-K-2Cl cotransporter 2A (NKCC2A), also known as the bumetanide-sensitive cotransporter 1 (BSC1), transports Na+, K+ and Cl- with a stoichiometry of 1:1:2. NKCC2A is considered a kidney specific cotransporter. It is abundantly expressed in apical membrane of the tubular cells in the thick ascending limb of the loop of Henle (TALH) and in the macula densa. However, NKCC2 has also been found at low levels in different cells, including insulin-secreting ones. This secondary active transporter uses the energy stored in the electrochemical gradients of Na and K maintained by the Na/K-ATPase located on the basolateral membrane of the TALH. The …

Ada Celebrates 70 Years Of Community Water Fluoridation At Ada 2015, American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

Dr. Francis G. Serio Honored With Ada 2015 Humanitarian Award, American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

Surgeon General Endorses Community Water Fluoridation, American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

The American Dental Association Welcomes Luiz Meirelles, D.D.S., M.S., Ph.D., American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

Vermont Dentist Installed As American Dental Association Trustee, American Dental Association

News Releases

This collection includes standard news releases, information kits and other documents distributed for publicity, information, announcements of events, etc. as issued from the ADA. Items included in this collection are archival and any costs, links, contact information, or other figures may be out of date. Please contact the ADA to verify information.

Loss Of Multidrug Resistance-Associated Protein 1 (Mrp1/Abcc1) Potentiates Doxorubicin-Induced Cardiotoxicity In Mice, Wei Zhang

Theses and Dissertations--Toxicology and Cancer Biology

Doxorubicin (DOX) is a broad-spectrum and effective chemotherapeutic agent, but its use in oncologic practice is limited by dose-dependent cumulative cardiotoxicity. DOX-induced cardiotoxicity is in large part due to its ability to cause oxidative stress. Multidrug resistance associated protein 1 (MRP1/ABCC1) is a member of the ATP-binding cassette (ABC) transporter superfamily. By effluxing a wide variety of endogenous and exogenous substrates, Mrp1 plays important physiological roles in multiple tissues and also protects normal tissues against toxicants. However, the role of MRP1 in heart is largely unknown.

The role of Mrp1 in DOX-induced cardiotoxicity was investigated in Mrp1 null (Mrp1-/-) and …

Analysis Of Humira, Electro-Acupuncture, And Pulsatile Dry Cupping On Reducing Joint Inflammation In Patients With Rheumatoid Arthritis, Natalie Noll

AUCTUS: The Journal of Undergraduate Research and Creative Scholarship

Humira, an anti-TNF drug aimed at decreasing inflammation in Rheumatoid Arthritis patients, can cause skin diseases from rashes to skin cancer. Humira works by blocking the chemical receptor RANKL which inhibits the production of osteoclasts. Osteoclasts are cells that attack and eat bone and cartilage therefore an inhibitory mechanism would cause inflammation.. By analyzing Humira’s effect on the human body, Humira can be compared to other treatments such as electro-acupuncture and pulsatile dry cupping to determine the viability of these alternative treatment methods in regards to their abilities to decrease inflammation in Rheumatoid Arthritis patients through blocking RANKL. An analysis …

Professional Product Review Vol. 10 No. 1, American Dental Association, Council On Scientific Affairs

Professional Product Review

A user-friendly newsletter from the ADA Council on Scientific Affairs offering scientifically sound, unbiased, and clinically relevant information to member dentists about professional dental products tested by the ADA. This collection is historical and may not reflect current standards. For up-to-date information contact the ADA.

Professional Product Review Vol. 10 No. 2, American Dental Association, Council On Scientific Affairs

Professional Product Review

A user-friendly newsletter from the ADA Council on Scientific Affairs offering scientifically sound, unbiased, and clinically relevant information to member dentists about professional dental products tested by the ADA. This collection is historical and may not reflect current standards. For up-to-date information contact the ADA.

Professional Product Review Vol. 10 No. 4, American Dental Association, Council On Scientific Affairs

Professional Product Review

A user-friendly newsletter from the ADA Council on Scientific Affairs offering scientifically sound, unbiased, and clinically relevant information to member dentists about professional dental products tested by the ADA. This collection is historical and may not reflect current standards. For up-to-date information contact the ADA.

Professional Product Review Vol. 10 No. 3, American Dental Association, Council On Scientific Affairs

Professional Product Review

A user-friendly newsletter from the ADA Council on Scientific Affairs offering scientifically sound, unbiased, and clinically relevant information to member dentists about professional dental products tested by the ADA. This collection is historical and may not reflect current standards. For up-to-date information contact the ADA.

Professional Product Review Vol. 10 No. 5, American Dental Association, Council On Scientific Affairs

Professional Product Review

A user-friendly newsletter from the ADA Council on Scientific Affairs offering scientifically sound, unbiased, and clinically relevant information to member dentists about professional dental products tested by the ADA. This collection is historical and may not reflect current standards. For up-to-date information contact the ADA.

The Therapeutic Targeting Of Folate Receptor Alpha Positive Tumors Via Folate Receptor Selective Novel 5- And 6- Substituted Pyrrolo [2,3-D]Pyrimidine Antifolates", Shermaine Kimberly Mitchell-Ryan

Wayne State University Dissertations

Ovarian Cancer is the fifth leading cause of cancer-related death of women in the United States. Epithelial Ovarian Cancer (EOC) constitutes 85-90% of malignancies within the ovary, with an alarming majority of these cases diagnosed at advanced stage. While most patients are initially highly responsive to the current treatment standard, there is a very high probability that they will recur with a drug resistant fatal disease. Currently there is no validated comprehensive model of disease progression for ovarian cancer, although tremendous progress has been made in understanding the origin of this disease and a putative precursor lesion has been identified …

Photodynamic Therapy As An Effective Therapeutic Approach In Mame Models Of Triple Negative And Inflammatory Breast Cancers, Neha Aggarwal

Wayne State University Dissertations

Introduction: Photodynamic therapy (PDT) is a minimally invasive, FDA approved therapy for

treatment of several indications including endobronchial and esophageal cancers that are

accessible to light. Triple negative breast cancer (TNBC) and inflammatory breast cancer (IBC)

are aggressive and lethal subtypes of breast cancer that spread to chest wall and dermal

lymphatics, respectively, sites that would be accessible to light. Both TNBC and IBC patients

have a relatively poor survival rate due to lack of targeted therapies. Use of PDT is

underexplored for breast cancers but has been proposed for treatment of subtypes for which a

targeted therapy is unavailable. …

2015 Transactions, American Dental Association

ADA Transactions

This item is part of the Transactions of the ADA, a serial publication of the annual activities of the ADA House of Delegates (HOD)/Board of Trustees (BOT). It is from the Transactions section, one of three subtitles that make up the full publication. Generally, the ADA Transactions are published in multiple volumes throughout the year. Pages from the Annual Reports and the Transactions are numbered consecutively (e.g. Annual Reports volume ends pg. 500 and Transactions volume starts at pg. 501). NOTE: All three subtitles are collectively known as the Transactions of the ADA or, alternatively, the ADA Transactions. Transactions refers …

Er Referral Models: Dental Intercept “Pay It Forward” Model — Calhoun County, Michigan, American Dental Association, Samanta Pearl

Action for Dental Health

No abstract provided.

Seniors With Diabetes-Investigation Of The Impact Of Semantic Auditory Distractions On The Usability Of A Blood Glucose Tracking Mobile Application, Jose A. Rivera Rodriguez

CCAC Theses and Dissertations

Diabetes is the seventh leading cause of death in the United States. With the population rapidly aging, it is expected that 1 out of 3 Americans will have diabetes by 2050. Mobile devices and mobile applications have the potential to contribute to diabetes self-care by allowing users to manage their diabetes by keeping track of their blood glucose levels. Usability is important for systems that help people self-manage conditions such as diabetes. Age and diabetes-related cognitive decline might intensify the impact of usability issues for the users who need these mobile applications the most. As highlighted by usability researchers, the …

The Use Of Rna Interference To Mitigate Pulmonary Fibrosis In Response To Asbestos Exposure, Sarah Kinsey

Undergraduate Theses, Professional Papers, and Capstone Artifacts

The adverse health effects of exposure to asbestos are widely known and have been well documented. When a person is diagnosed with asbestosis, a chronic lung disease caused by inhaling asbestos fibers, few treatment options exist, none of which halt or reverse the progression of the disease. The rapidly growing field of gene therapy offers new avenues for potential treatments worthy of investigation. The detrimental effects of asbestos exposure are due to the physiological response of the lungs to asbestos fibers in the form of fibrosis, a result of excess extracellular collagen deposition. A protein called SPARC (Secreted Protein Acidic …

Effectiveness Of A Volunteer Transportation Program To Increase Access To Healthcare In Vietnam, Kyla Crisp

Undergraduate Theses, Professional Papers, and Capstone Artifacts

As a part of the Global Leadership Initiative capstone project at the University of Montana, my group created a website and transportation program that works to increase access to healthcare in Missoula, Montana. Ancillary aspects of healthcare such as health literacy, transportation, housing, and food are all major factors affecting a person’s health. Our project titled UM Volunteers for Global Health Access seeks to unite University students and the low-income population in Missoula in order to provide rides to healthcare appointments. The transportation framework will allow patients at Partnership Health Center to be connected with University of Montana student volunteers. …

All Payer Hospital Regulations, Sam Lovejoy, Heath Ashford, William K. Willis, Alberto Coustasse

Management Faculty Research

Introduction: An all-payer system is a price setting system where rates of payment for healthcare services have not been negotiated between a hospital or health system or a payer but instead by a third party organization, such as Maryland’s Health Services Cost Review Commission (HSCRC), who sets most hospital rates that all payers agree to honor. All payer hospitals focus is on legislative principles in an effort to control costs.

Methods: The methodology for this study was a literature review compiled with overview of All-payer hospital systems and its utilization in a hospital setting. All articles prior to 2000 were …