Biochemistry, Biophysics, and Structural Biology Commons^™

Special Issue On The Third Workshop On Biological Mentality, Kenneth A. Augustyn

Michigan Tech Publications, Part 1

The Third Workshop on Biological Mentality was held from September 23, 2019 to March 2, 2020 as a series of twenty-one Monday online conferencing sessions, each consisting of a talk followed by a Q&A discussion. Like the two previous workshops [1, 2], the objective of this workshop was to seek a deeper level of understanding the physical foundations of biological mentality (whether conscious or nonconscious).

Consciousness As A Factor In Evolution, Kenneth A. Augustyn

Michigan Tech Publications, Part 1

What I call the mind began as a non-conscious robotic biochemical process control system in the very earliest forms of life. As life evolved, problems in control became more difficult and exceeded the computational capabilities of the organisms. Nature discovered a means of transcending computable physical processes resulting in non-computational subjective mental capabilities that, while still not conscious, had a degree of genuine autonomy from the physical world. These autonomous subjective wants and goals now affected the course of (but not the mechanism of) evolution. The integrated amalgam of robotic and transrobotic unconscious capabilities eventually gave rise to consciousness, which …

Cold Atmospheric Plasma Induces Silver Nanoparticle Uptake, Oxidative Dissolution And Enhanced Cytotoxicity In Glioblastoma Multiforme Cells, Eline Manaloto, Aoife Gowen, Anna Lesniak, Zhonglei He, Alan Casey, Patrick J. Cullen, James Curtin

Articles

Silver nanoparticles (AgNP) emerged as a promising reagent for cancer therapy with oxidative stress implicated in the toxicity. Meanwhile, studies reported cold atmospheric plasma (CAP) generation of reactive oxygen and nitrogen species has selectivity towards cancer cells. Gold nanoparticles display synergistic cytotoxicity when combined with CAP against cancer cells but there is a paucity of information using AgNP, prompting to investigate the combined effects of CAP using dielectric barrier discharge system (voltage of 75 kV, current is 62.5 mA, duty cycle of 7.5kVA and input frequency of 50–60Hz) and 10 nm PVA-coated AgNP using U373MG Glioblastoma Multiforme cells. Cytotoxicity in …

Effect Of Mptp On Α-Synuclein Spreading, Accumulation And Toxicity In Mice With Intrastriatal Innoculation Of Human Α-Synuclein Preformed Fibril, Madiha Mohieldin Merghani

Theses

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder, characterized by abnormal accumulation of interneuronal inclusions of α-synuclein (α-syn) known as Lewy bodies (LBs) and Lewy neurites (LNs), and significant loss of dopamine neurons in the substantia nigra pars compacta (SNc) region of the brain. Recent evidence suggests that intrastriatal inoculation of α-syn Preformed Fibril (PFF) into mice induces PD-like LBs and LNs pathology formed by aggregated α-syn in anatomically interconnected brain regions which needs several months of incubation to develop the pathology. In the present study, we have evaluated the effect of different doses of 1-methyl, 4-phenyl, …

Quantifying The Heterogeneity Of The Immunoglobulin G N-Glycome In An Ageing Australian Population: The Busselton Healthy Ageing Study, Alyce Russell

Theses: Doctorates and Masters

The use of immunoglobulin G N-glycomics to study chronic non-communicable disorders and other complex phenotypes emerged following the Human Genome Project. The consortium discovered that most phenotypes were too complex to be explained by genetics alone. Thus, the biological importance of epigenetics was recognised; heritable modifications to gene expression rather than the genome itself. Nglycosylation is a form of epigenetic regulation known as a post-translational modification. It stabilises the immunoglobulin G structure and alters downstream responses elicited by the antibody and is extensively studied as a candidate biomarker in the post-genomic era.

The N-glycosylation of immunoglobulin G itself is complex, …

Size-Dependent Interactions Of Lipid-Coated Gold Nanoparticles: Developing A Better Mechanistic Understanding Through Model Cell Membranes And In Vivo Toxicity, Arek M. Engstrom, Ryan A. Faase, Joe E. Baio, Marilyn R. Mackiewicz, Stacey L. Harper

Chemistry Faculty Publications and Presentations

Introduction: Humans are intentionally exposed to gold nanoparticles (AuNPs) where they are used in variety of biomedical applications as imaging and drug delivery agents as well as diagnostic and therapeutic agents currently in clinic and in a variety of upcoming clinical trials. Consequently, it is critical that we gain a better understanding of how physiochemical properties such as size, shape, and surface chemistry drive cellular uptake and AuNP toxicity in vivo. Understanding and being able to manipulate these physiochemical properties will allow for the production of safer and more efficacious use of AuNPs in biomedical applications.
Methods and Materials: Here, …

Archaeosine Modification Of Archaeal Trna - A Role In Structural Stabilization, Ben Turner, Brett W. Burkhart, Katrin Weidenbach, Robert Ross, Patrick A. Limbach, Ruth A. Schmitz, Valérie De Crécy-Lagard, Kenneth M. Stedman, Thomas J. Santangelo, Dirk Iwata-Reuyl

Biology Faculty Publications and Presentations

Archaeosine (G+) is a structurally complex modified nucleoside found quasi-universally in the tRNA of Archaea and located at position 15 in the dihydrouridine loop, a site not modified in any tRNA outside of the Archaea. G+ is characterized by an unusual 7-deazaguanosine core structure with a formamidine group at the 7-position. The location of G+ at position 15, coupled with its novel molecular structure, led to a hypothesis that G+ stabilizes tRNA tertiary structure through several distinct mechanisms. To test whether G+ contributes to tRNA stability and define the biological role of G+, we investigated the consequences of introducing targeted …

A Kinesin Adapter Directly Mediates Dendritic Mrna Localization During Neural Development In Mice, Hao Wu, Jing Zhou, Tianhui Zhu, Ivan Cohen, Jason Dictenberg

Publications and Research

Motor protein-based active transport is essential for mRNA localization and local translation in animal cells, yet how mRNA granules interact with motor proteins remains poorly understood. Using an unbiased yeast two–hybrid screen for interactions between murine RNA-binding proteins (RBPs) and motor proteins, here we identified protein interaction with APP tail-1 (PAT1) as a potential direct adapter between zipcode-binding protein 1 (ZBP1, a β-actin RBP) and the kinesin-I motor complex. The amino acid sequence of mouse PAT1 is similar to that of the kinesin light chain (KLC), and we found that PAT1 binds to KLC directly. Studying PAT1 in mouse …

The Vimentin Rod Domain Blocks P-Selectin-P-Selectin Glycoprotein Ligand 1 Interactions To Attenuate Leukocyte Adhesion To Inflamed Endothelium, Fong Wilson Lam, Cameron August Brown, Christian Valladolid, Dabel Cynthia Emebo, Timothy Gerald Palzkill, Miguel Angel Cruz

Faculty, Staff and Students Publications

Acute inflammation begins with leukocyte P-selectin glycoprotein ligand-1 (PSGL-1) binding to P-selectin on inflamed endothelium and platelets. In pathologic conditions, this process may contribute to secondary organ damage, like sepsis-induced liver injury. Therefore, developing novel therapies to attenuate inflammation may be beneficial. We previously reported that recombinant human vimentin (rhVim) binds P-selectin to block leukocyte adhesion to endothelium and platelets. In this study, we used SPOT-peptide arrays to identify the rod domain as the active region within rhVim that interacts with P-selectin. Indeed, recombinant human rod domain of vimentin (rhRod) binds to P-selectin with high affinity, with in silico modeling …

Acute Lymphoblastic Leukemia Presenting Initially As Spinal Cord Compression: When Chemotherapy Alone Is Enough, Albert Jang, Kallie N Kram, Scott N Berger, Mahmoud R Gaballa, Lee B Lu, David R Dunaway, Courtney N Miller-Chism

Faculty, Staff and Students Publications

Spinal cord compression (SCC) is a rare initial presentation and complication of acute lymphoblastic leukemia (ALL) with nearly all reported cases occurring in the pediatric population. We report a 38-year-old previously healthy man who presented with acute on chronic lower back pain, gait instability, urinary retention, and severe thrombocytopenia. Radiologic examination revealed two soft tissue masses of the thoracic spine associated with compression fractures causing spinal canal narrowing and cord compression. Bone marrow biopsy confirmed the diagnosis of ALL. Immediate initiation of high-dose corticosteroids and systemic chemotherapy resolved the patient's symptoms without radiation therapy or surgical intervention. After two courses …

Aromatase Inhibitors Plus Weight Loss Improves The Hormonal Profile Of Obese Hypogonadal Men Without Causing Major Side Effects, Georgia Colleluori, Rui Chen, Christie G Turin, Francesca Vigevano, Clifford Qualls, Biju Johnson, Sanjay Mediwala, Dennis T Villareal, Reina Armamento-Villareal

Faculty, Staff and Students Publications

Objective: In obese men, the increased expression of the aromatase enzyme in adipose tissue leads to high conversion of androgens to estrogens contributing to hypogonadotropic hypogonadism (HHG). Our objective is to evaluate efficacy and safety of weight loss (WL) plus aromatase inhibitor (AI) therapy in severely obese men with HHG. We hypothesize that AI+WL will be more effective as compared to WL alone in improving the hormonal profile, thus muscle strength and symptoms of HHG (primary outcomes), with no significant adverse effects on lean mass, metabolic profile, and bone mineral density (secondary outcomes).

Design: Randomized double-blind placebo-controlled pilot trial.

Methods: …

Pregnancy And Lactation In A 67-Year-Old Elderly Gravida Following Donor Oocyte, Leila Magistrado, Mary C Tolcher, Anju Suhag, Sonal Zambare, Kjersti M Aagaard

Faculty, Staff and Students Publications

There is limited data on the anticipated perinatal course among gravidae in their sixth and seventh decades. Our objective was to describe the relatively uncomplicated prenatal, intrapartum, and postpartum course of a 67-year-old essential primigravida. Briefly, our patient conceived a singleton pregnancy via IVF with donor oocytes, then presented at 13 6/7 weeks of gestation to initiate prenatal care. Her medical history was significant for chronic hypertension, hyperlipidemia, and obesity. Her cardiac function was monitored throughout pregnancy, and she delivered at 36 1/7 weeks by cesarean for a decline in left ventricular function with mitral regurgitation. Her intrapartum and postpartum …

Spironolactone In Pulmonary Arterial Hypertension: Results Of A Cross-Over Study, Zeenat Safdar, Adaani Frost, Arya Basant, Anita Deswal, E O'Brian Smith, Mark Entman

Faculty, Staff and Students Publications

The renin–angiotensin–aldosterone system is implicated in the pathophysiology of pulmonary arterial hypertension. We undertook this study to determine the effects of spironolactone, a mineralocorticoid receptor blocker, on collagen metabolism in pulmonary arterial hypertension patients. After obtaining institutional review board approval and informed consent, 42 pulmonary arterial hypertension patients were prospectively enrolled and 35 patients completed the 16-week randomized double-blinded crossover clinical trial. Subjects received 50 mg spironolactone or placebo and at the end of week 8, treatment arm was switched. Circulating levels of collagen biomarkers, brain natriuretic peptide, and aldosterone levels were measured, and six-minute walk distance, liver function tests, …

Meta-Analysis Comparing Watchmantm And Amplatzer Devices For Stroke Prevention In Atrial Fibrillation, Indranill Basu Ray, Dibbendhu Khanra, Sumit Shah, Sudhanva Char, Xiaoming Jia, Wilson Lam, Nilesh Mathuria, Mehdi Razavi, Bhavna Jain, Dhanunjaya Lakkireddy, Saibal Kar, Andrea Natale, Adedayo Adeboye, John Lynn Jefferies, Sripal Bangalore, Samuel Asirvatham, Mohammad Saeed

Faculty, Staff and Students Publications

Background: For patients with atrial fibrillation who are at high risk for bleeding or who cannot tolerate oral anticoagulation, left atrial appendage (LAA) closure represents an alternative therapy for reducing risk for thromboembolic events.

Objectives: To compare the efficacy and safety of the Amplatzer and Watchman^TM LAA closure devices.

Methods: A meta-analysis was performed of studies comparing the safety and efficacy outcomes of the two devices. The Newcastle-Ottawa Scale was used to appraise study quality.

Results: Six studies encompassing 614 patients were included in the meta-analysis. Overall event rates were low for both devices. No significant differences between the …

Development Of Assessment Tools Of Package/Product Systems For A Sustainable Food Chain, Kompal Joshi

Doctoral

Post-harvest life of fresh produce is limited due to high metabolic activity and microbial spoilage. Modified atmosphere packaging (MAP) has proven to be one of the most effective techniques to extend the shelf life of fresh produce commercially. Obtaining of an optimum concentration of oxygen and carbon dioxide inside the package depends upon the product properties, the environmental conditions of the cold chain, the permeable film, some of which are subjected to natural variability during the food distribution chain. This variability may generate produce that is out of specification that will lead to food waste. Uncertainty analysis of this problem …

Amyloid Proteins And Fibrils Stability, Farbod Mahmoudinobar

Dissertations

Compared to globular proteins that have a stable native structure, intrinsically disordered peptides (IDP) sample an ensemble of structures without folding into a native conformation.One example of IDP is the amyloid-beta(Abeta) protein which is the main constituent of senile plaques in the brain of Alzheimer's patients.Understanding the process by which IDPs undergo structural changes to form oligomers that eventually aggregate into senile plaques/amyloid fibrils may significantly advance the development of novel therapeutic methods to treat neurodegenerative diseases, for which there is no cure to date. This dissertation has two main objectives. The first one is to investigate and identify structural …

Architecture Of The Chromatin Remodeler Rsc And Insights Into Its Nucleosome Engagement., Avinash B Patel, Camille M Moore, Basil J Greber, Jie Luo, Stefan A Zukin, Jeff Ranish, Eva Nogales

Articles, Abstracts, and Reports

Eukaryotic DNA is packaged into nucleosome arrays, which are repositioned by chromatin remodeling complexes to control DNA accessibility. The

Does The Seedling Emergence Technique Limit The Detection Of Seeds Of Miombo Species In Miombo Woodlands?, Halima M. Amir, Mkabwa L. K Manoko

Journal of Humanities and Social Sciences

Seedling emergence technique frequently used in soil seed bank studies indicates that seeds of Miombo species are not present in the soil seed bank. Does this method limit the detection of seeds of Miombo species in the soil seed bank? This question has not been investigated systematically. The present study aims to find out whether the seedling emergency method limits the detection of seeds of Miombo species in the soil seed bank of Miombo woodlands. In the investigation, seedling emergence and extraction methods were used to estimate soil seed bank in Miombo woodlands. Data were obtained from 50 circular plots …

Robust Cullin-Ring Ligase Function Is Established By A Multiplicity Of Poly-Ubiquitylation Pathways, Spencer Hill, Kurt Reichermeier, Daniel C. Scott, Lorena Samentar, Jasmin Coulombe-Huntington, Luisa Izzi, Xiaojing Tang, Rebeca Ibarra, Thierry Bertomeu, Annie Moridian, Michael J. Sweredoski, Nora Caberoy, Brenda A. Schulman, Frank Sicheri, Mike Tyers, Gary Kleiger

Life Sciences Faculty Research

The cullin-RING ligases (CRLs) form the major family of E3 ubiquitin ligases. The prototypic CRLs in yeast, called SCF enzymes, employ a single E2 enzyme, Cdc34, to build poly-ubiquitin chains required for degradation. In contrast, six different human E2 and E3 enzyme activities, including Cdc34 orthologs UBE2R1 and UBE2R2, appear to mediate SCF-catalyzed substrate polyubiquitylation in vitro. The combinatorial interplay of these enzymes raises questions about genetic buffering of SCFs in human cells and challenges the dogma that E3s alone determine substrate specificity. To enable the quantitative comparisons of SCF-dependent ubiquitylation reactions with physiological enzyme concentrations, mass spectrometry was employed …

Effects Of Seasons And Zonation On Biochemical Contents Of Two Seagrass Species Along Dar Es Salaam Coast, Tanzania, Wamwi M. Mbaga, Esther F. Mvungi

Tanzania Journal of Science

Accumulation and allocation of biochemicals in plants are affected by various factors. The influence of seasons and vertical zonation on biochemical contents of seagrasses Cymodocea rotundata and Thalassia hemprichii from Mjimwema seagrass meadow along the coast of Dar es Salaam were assessed. Samples were collected in 2016 during wet/rainy (April–May) and dry (June–July) seasons. Concentrations of crude protein, soluble carbohydrates, phosphorus, lipid, and proline were determined using standard methods. Significant higher levels of phosphorus, lipid, protein and proline were observed during the dry season than in wet season (p < 0.05). Likewise, seagrass population occurring at the shore zone expressed higher levels of biochemical contents than those found at the subtidal zones. The highest concentration of protein was recorded in Thalassia hemprichii (5.8 mg/g dw)), while those of lipid and carbohydrates (27.1 and 53.1 mg/g dw, respectively) were recorded in Cymodocea rotundata. The two species studied did not vary significantly in their biochemical concentrations in both seasons. Generally it was observed that the concentrations of studied biochemicals were up-regulated during the dry season and varied depending on the locations where the seagrass grow. Thus, both season and zonation played roles in biochemical accumulation in the seagrasses understudy, however not interactively.