Biochemistry, Biophysics, and Structural Biology Commons^™

Cytidine Triphosphate Specifically Modulates Parb-Mediated Dna Compaction: Insights From Single-Molecule Analysis And Parb C-Terminal Lysine Mutagenesis, Lois Akosua Serwaa

Theses and Dissertations

ParB is a central player in bacterial chromosome segregation, and cytidine triphosphate (CTP) is known to modulate its DNA compaction activity. This study explored whether CTP’s regulatory effect is due to specific molecular interactions beyond its known CTP-binding pocket. Using single-molecule flow-stretching and TIRF microscopy, we showed that CTP significantly reduces DNA compaction by wild-type Bacillus subtilis ParB, while ATP has no effect, supporting the hypothesis that CTP acts through specific recognition rather than general charge. CTP’s modulatory effect persisted across C-terminal domain (CTD) lysine mutants. Compaction was reduced in wild-type and K255A but abolished in K252A and K259A. The …

Oxytocin As A Possible Vegf Inhibitor For Treatment Of Diabetic Retinopathy, Daira Yepez

Theses and Dissertations

Diabetic retinopathy (DR) is a major complication of diabetes and a leading cause of vision loss largely driven by the overexpression of vascular endothelial growth factor (VEGF), which promotes neovascularization and vascular permeability in the retina. Current treatments, primarily anti-VEGF injections, inhibit the effects of VEGF once it has been secreted but can be ineffective in a certain subset of patients. Recent studies suggest that oxytocin (OXT), a neuropeptide mainly known for its roles in reproduction and social bonding, may downregulate VEGF expression. This study aimed to investigate whether OXT influences VEGF secretion in the human retinal pigment epithelial (RPE) …

L-Quebrachitol Modulates The Anti-Convulsant Effects Of Carbamazepine Possibly Through Voltage-Gated Sodium Channel Blocking Mechanism In Chicks: In Vivo And In Silico Studies, Asifa Asrafi, Mohammad Aslam, Ali G. Alkhathami, Md. Sakib Hossain, Imam Hossen Rakib, Md. Sakib Al Hasan, Feroz Khan Nun, Md. Faisal Amin, Muhammad Torequl Islam

School of Integrative Biological & Chemical Sciences Faculty Publications

Introduction: L-Quebrachitol (LQB), a naturally occurring bioactive compound, exhibits anti-inflammatory, anti-oxidant, anti-cancer, and anti-diabetic properties. However, its therapeutic potential in convulsant management remains largely unexplored. The objective of this study was to investigate the anticonvulsant effects of LQB in an In Vivo model and to examine its molecular interactions via In Silico docking simulations.

Methods: In the In Vivo study, pentylenetetrazol (PTZ) was administered intraperitoneally (i.p.) at 80 mg/kg to induce convulsions, and the test animals were treated orally with three doses of LQB (1, 5, and 10 mg/kg), with carbamazepine (CBZ) at 80 mg/kg as a standard drug.

Results: …

Investigating The Role Of Metallothioneins In Fungal Iron Homeostasis, David Eap

Theses and Dissertations

The pathogenic fungi Aspergillus fumigatus requires metals to survive and infect humans, but metal overload can be detrimental. Metallothioneins (MTs) are small, cysteine-rich proteins that alleviate metal toxicity by binding excess metals (typically Zn or Cu) for storage or delivery. A recent report indicates that the Fe-S cluster binding glutaredoxin GrxD and the putative Cu-MT CmtA were interacting under high iron conditions in A. fumigatus. We hypothesize that this MT may have a role in binding iron or Fe-S clusters under iron overload conditions to prevent iron toxicity. We also aim to characterize this new MT by determining its …

Using Radium Isotopes To Compare Nutrient Inputs Via Submarine Groundwater Discharge To Offshore Export On The West Florida Shelf, Andrew L. Lindgren

OES Theses and Dissertations

Radium isotopes have been used to trace submarine groundwater discharge (SGD) and associated nutrient and metal inputs into the coastal ocean. They have also been used to estimate rates of diffusive mixing and export fluxes of dissolved constituents offshore. However, use of both approaches in tandem to determine the fate of groundwater inputs after they enter the coastal ocean is still relatively unexplored. Radium isotopes and nutrients were measured in two cross-shelf cruises on the West Florida Shelf in different seasons and in quarterly sampling of offshore wells. Through 226Ra mass balance and 223Ra-derived diffusive mixing rates, inputs of nutrients …

From Differentiation To Disease: Cyclin C Directly Coordinates Transcription And Mitochondrial Dynamics, Alicia Campbell

Theses and Dissertations

Organelle crosstalk is essential for coordinating cellular responses to various external cues, including stress and differentiation. Two key organelles, the nucleus and mitochondria, engage in extensive crosstalk to manage responses to a range of environmental and developmental signals. Complex processes such as stem cell differentiation and neuronal development rely on organelle crosstalk. Both processes integrate changes in gene expression with cytosolic and organellar remodeling. However, it remains unclear how these two complex processes are coordinated to achieve the desired outcome. This project concentrates on cyclin C (CCNC), a component of the Mediator Kinase Module (MKM), and its role in directly …

A Customizable Ligand-Conjugate System For Investigation And Detection Of Ghrelin O-Acyltransferase, Amber Ford

Dissertations - ALL

Ghrelin is a 28 amino acid peptide hormone responsible for a variety of physiological functions. Ghrelin signals these functions via its cognate receptor, GHSR, after an essential post translational modification which acylates its third serine. The acylation of ghrelin is facilitated by the enzyme ghrelin O-acyltransferase (GOAT) for which ghrelin is the only known substrate. Canonically, GOAT acylates ghrelin in the endoplasmic reticulum before it is further processed and secreted in circulation. Recent studies, however, have detected GOAT in the cytoplasm, plasma membrane, and in circulation in extracellular vesicles. Furthermore, GOAT has been identified as a potential prostate cancer (PCa) …

Synthesis Of Carboxymethyl Cellulose From Nypa Fruticans For Coating Metformin On Zn-Based Metal-Organic Framework Nanohybrid As A Bionanocomposite Drug Delivery System, Delviani Delviani, Viola Giary Rizkillah Maharani, Putri Nur Shadrina, Tri Warni, Regina Wan Azizah, Indra Lasmana Tarigan, Madyawati Latief

Makara Journal of Science

Diabetes is a common and rapidly spreading disease that affects 6.6% of the world’s population. Metformin hydrochloride (HCl) is an effective oral pharmacological treatment for type 2 diabetes mellitus (T2DM) patients because of its capability to reduce glucose levels and the risk of hypoglycaemia. However, gastrointestinal sensitivities to this drug can cause diarrhoea, nausea, vomiting and stomach ache. An alternative is controlled release technology by coating metformin with carboxymethyl cellulose (CMC) and zinc-metal-organic framework (Zn-MOF) through the encapsulation method. Therefore, this study aimed to coat metformin formulations using CMC in a Zn-MOF to control release into the body and minimise …

Microscopic Nucleic Acid-To-Protein Ratio: A Label-Free Approach For Pancreatic Cancer Detection, Sky Gao, Keerthi Priya Jangili, Alfred Akinlalu, Emmanuel Ogberefor, Tommy Gao, Kalpana Devaraj, Dali Sun

Electrical and Computer Engineering: Faculty Scholarship

Accurate and timely diagnosis remains a major clinical challenge, hindered by the limitations of conventional histopathological methods, which often rely on labor-intensive staining protocols and subjective interpretation by specialized pathologists. These methods can fail to capture the full molecular and phenotypic heterogeneity of tumors, leading to increased diagnostic time, cost, and variability. To overcome these challenges, we developed a novel label-free ultraviolet (UV) microscopic imaging technique that exploits the intrinsic optical absorption properties of cellular nucleic acids and proteins. By modifying standard brightfield microscopes, our approach quantitatively measures the nucleic acid-to-protein ratio (NPr), enabling high-resolution visualization and discrimination between malignant …

Photo-Crosslinked Persistent Micelle Templates With Near Universal Solvent Compatibility, Coby S. Collins, Mengxue Zhang, Cj Strurgill, Christian X. Ruff, Bryce Melton, Morgan Stefik

Faculty Publications

The controlled preparation of porous nanomaterials from block polymer templates is important for diverse applications from energy devices to optical coatings and sorbents. The architectural dimensions determine the overall performance for many of these applications, however the independent control of these dimensions has remained limited to a narrow range of solvent conditions for kinetically trapped (“persistent”) micelle templates. Polymers with a photo-reactive chemistry are shown to enable cross-linked micelle templates that universally remain persistent under diverse solvent conditions. Specifically, poly(poly(ethylene glycol methacrylate))-b-poly(butyl methacrylate-co-coumarin methacrylate) (OBC) was prepared by RAFT polymerization and the resulting micelles were crosslinked …

Beyond Diversity Initiatives: Building A Community Of Care In Scientific Societies, Richelle L. Tanner, Kathryn Wilsterman

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

"In this Professional Biologist article, we present one such reframing that centers individualized care through structural changes. We argue that psychological and sociological motivations of belonging and social capital in the academy are funda- mental challenges contributing to the cultural problems within STEM fields and are particularly present within professional scientific societies. In support of this argument, we present survey- based data alongside significant literature from the humanities. In this reframing supported by existing organizational culture literature and our survey results, we suggest that scientific societies are uniquely positioned to promote significant cultural change within STEM by focusing on building …

Antioxidant Activity Of Caesalpinia Sappan Heartwood Extracts Against Hydrogen Peroxide-Induced Oxidative Damage In Mrc-5 Cell Lines, Supranee Kongkham, Aylada Kaenu

Chulalongkorn Medical Journal

Background: C. sappan heartwood extract is a good antioxidant potential natural compound against oxidative stress. A few data have been reported with those of value using cell base assay, especially in normal human lung fibroblast cells.

Objective: The heartwood extracts of C. sappan were obtained with different ethanol concentrations and investigated on the antioxidant capacity on human lung fibroblast MRC-5.

Method: The crude extracts were subjected to antioxidant activity assays based on free radical scavenging activity by Chemi-based assay and cell-based assay (in-vitro lipid peroxidation, CAT and SOD) using MRC-5 cells.

Result: The study shown that …

The Structure Of The Drp1 Lattice On Membrane, Kristy Rochon, Anelise N. Hutson, Jason A. Mears

Faculty Scholarship

Mitochondrial health relies on the membrane fission mediated by dynamin-related protein 1 (Drp1). Previous structural studies of Drp1 on remodeled membranes were hampered by heterogeneity, leaving a critical gap in the understanding of the mitochondrial fission mechanisms. Here we present a cryo-electron microscopy structure of full-length human Drp1 decorated on membrane tubules. Using the reconstruction of average subtracted tubular regions (RASTR) technique, we report that Drp1 forms a locally ordered lattice along the tubule without global helical symmetry. The filaments in the lattice are similar to dynamin rungs with conserved stalk interactions. Adjacent filaments are connected by GTPase domain interactions …

Design And Evaluation Of An Innovative Biomimetic Coral Transport Container, John-Christopher L. Calulo, Wilfredo Y. Licuanan, Leah D. Madrazo, Dana Isabelle P. Villano, Angel Nicole B. Villanueva

Sinaya: A Philippine Journal for Senior High School Teachers and Students

Coral reefs are vulnerable to disruptive human activities such as pollution, overfishing, and coastal development—degrading water quality and reef structures. Active reef restoration entails temporarily relocating several corals to aquaculture facilities to achieve successful rehabilitation; however, current coral transport methods pose certain risks, such as stress-induced mortality, which can result from physical damage during transportation. Existing studies on coral transport have explored various techniques for collecting, shipping, and maintaining live coral specimens. The design consists of petal-shaped areas where the waves gather, akin to a coral reef’s grooves, separated by wedges—the spurs—that cause waves to divide. The different design modifications …

Analysis Of Synaptotagmin Isoforms In Lßt2 Gonadotrophs, Caitlin Vahl

Undergraduate Theses, Capstones, and Recitals

The anterior pituitary is comprised of five cell types which secrete regulatory hormones into the bloodstream. Specifically, gonadotrophs synthesize and release sex hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH) in response to gonadotropin-releasing hormone (GnRH). GnRH signals from the hypothalamus regulate the differential secretion of LH and FSH from the anterior pituitary. Exocytosis of FSH and LH from dense core vesicles (DCVs) occurs in response to an intracellular calcium signal, sensed by the synaptotagmins proteins. Various isoforms of synaptotagmins exist and each isoform has varying affinity for calcium, causing calcium-regulated exocytosis to be finely controlled. Because LH and FSH …

Photochemistry Of Quinones And Combustion-Derived Particles, Desiree J. Sarmiento

Electronic Theses and Dissertations

Quinones are ubiquitous species that can be produced from the photochemical aging of combustion-derived particles (CDPs). Polycyclic aromatic hydrocarbons (PAHs) are a major component of CDPs and are precursors to quinones and other oxidized products (OPAHs). My work first expanded on the PAH and OPAH photochemistry research of Dr. John Haynes, who showed that anthracene (ANT) oxidizes into 1,4-naphthoquinone (1,4-NAPQ), 1,4-anthraquinone (1,4-ANTQ), and 9,10-anthraquinone (9,10-ANTQ), and of Dr. Heather Runberg, who demonstrated the ability of ANT and these quinones to generate reactive oxygen species (ROS). Then at the Pacific Northwest National Laboratory (PNNL), I was given the opportunity to investigate …

Foldit Education Mode, Brett Schulz

Electronic Theses and Dissertations

Foldit education mode is a puzzle campaign within the protein folding video game Foldit. Education mode, initially designed as a classroom supplement for undergraduate biochemistry courses, has been expanded to provide a more comprehensive learning tool to players without a background in biochemistry. The edited and added levels teach players about protein biochemistry through playing puzzles designed to convey information and gameplay mechanics. The new Foldit education mode campaign features 49 levels grouped into 11 categories. The campaign has 6 new levels designed specifically for education mode and 4 levels adapted from the traditional Foldit campaign for use within education …

Carbon Monoxide Releasing Polymeric Micelles, Riya Joshi

Electronic Theses and Dissertations

Carbon monoxide (CO), traditionally known as a toxic gas, has emerged as a potential therapeutic agent due to its cytoprotective, anti-inflammatory, and vasodilatory properties. This study explores the development of CO-releasing polymeric micelles as a controlled delivery system for biomedical applications. Using ring-opening metathesis polymerization (ROMP), we synthesized diblock copolymers incorporating CO-releasing moiety diphenylcyclopropenone (DPCP) with hydrophilic polyethylene glycol (PEG) to enhance solubility and stability of the overall CO releasing system. Dynamic light scattering (DLS) and electron microscopy (EM) confirmed the formation of well-defined micelles, while fluorescence assays demonstrated efficient CO release with the use of Iridium photocatalyst under 470 …

The Anticancer Activity Of Novel Chromene Derivatives Against Colorectal Cancer Cells, Rym Magramane

Thesis/ Dissertation Defenses

Colorectal cancer (CRC) stands as the third most common cancer globally, accounting for nearly 10% of all newly diagnosed cancer cases. In the UAE, CRC was ranked as the third most frequently diagnosed malignancy, and the leading cause of cancer-associated deaths in 2023. Standard CRC treatment strategies include surgical resection, chemotherapy, immunotherapy, targeted therapy, or a combination of all, depending on the cancer stage and molecular profile. Despite these interventions, disease recurrence is experienced by a considerable number of cancer patients. Hence, there is an urgent need to develop novel alternative treatments to overcome poor prognosis. Recently, cancer research has …

Role Of Gut-Liver-Brain Axis In Neuropsychiatric Symptoms Of Parkinson’S Disease, Raveena Dhanani Ratnayake

Student Theses and Dissertations

Neuropsychiatric symptoms (NPS), such as depression, and anxiety, and mild cognitive impairment (MCI), often precede motor symptoms in Parkinson’s disease (PD), highlighting the need for early biomarkers and mechanistic insights. Gut-microbiome-related metabolites, including secondary bile acids, influence lipid homeostasis and mitochondrial function, impacting neuropsychiatric and neurodegenerative disorders. This study examines metabolic alterations in PD, focusing on lipid metabolism, bile acids, acylcarnitine, and amino acids. Our findings showed significant changes in lipid metabolism, transsulfuration pathway, bile acids, acylcarnitine, and amino acids in PD severity and NPS. Specific lipid subclasses were linked to NPS, cognitive impairment, and motor impairment. Given the limited …

Highly Adaptable Dendrimer Gel Nanoparticles With Dual Targeting Of Upar And Ribonucleotide Reductase R2 For Better Retention And Improved Therapeutic Outcomes In Triple-Negative Breast Cancer, Hsin Yin Chuang, Da Huang, Lin Qi, Vidit Singh, Anna Chernatynskaya, Yue-Wern Huang, Hu Yang

Biological Sciences Faculty Research & Creative Works

Triple-negative breast cancer (TNBC) accounts for approximately 15% of breast cancers and lacks estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), rendering it unresponsive to hormonal or anti-HER2 therapies. Due to its poor prognosis and limited treatment options, there is an urgent need for targeted therapies. In this study, we developed highly adaptable polyamidoamine (PAMAM) dendrimer-based gel nanoparticles with dual-targeting capabilities against urokinase-type plasminogen activator receptor (uPAR) and ribonucleotide reductase R2 (R2). These nanoparticles were designed to target both TNBC cells and cancer-associated stromal cells by leveraging uPA-uPAR interactions and delivering the antisense oligonucleotide …

Why Acromegaly Dies: A Systematic Review, Isam Noori Salman, Safaa Ehssan Atta, Baydaa Ahmed Abed, Noor Ulhuda G. Mohammed

Maaen Journal for Medical Sciences

Acromegaly is a rare endocrine clinical syndrome characterized by long-term elevated production of growth hormone (GH) due to a pituitary adenoma tumor. The main problem of acromegaly patients (AC-PTs) is prolonged elevated GH concentration, which leads to increased insulin-like growth factor 1 (IGF-1) production, causing the characteristic tissue and bone overgrowth. The appearance of diabetes in AC-PTs was linked with the high risks of cardiovascular morbidity, indicating that individuals with both conditions face heightened health challenges. Acromegaly typically has a higher cancer incidence rather than the general population. Without early diagnosis and effective treatment, excess GH can have widespread systemic …

Human Gut Commensal Alistipes Timonensis Modulates The Host Lipidome And Delivers Anti-Inflammatory Outer Membrane Vesicles To Suppress Colitis In An Il10-Deficient Mouse Model, Ethan Older, Mary K. Mitchell, Andrew Campbell, Xiaoying Lian, Michael Madden, Yuzhen Wang, Lauren E. Van De Wal, Thelma Zaw, Brandon N. Vanderveen, Rodney Tatum, E. Angela Murphy, Yan-Hua Chen, Daping Fang, Melissa Ellermann, Jie Li

Faculty Publications

Correlative studies have linked human gut microbes to specific health conditions. Alistipes is one such microbial genus negatively linked to inflammatory bowel disease (IBD). However, the protective role of Alistipes in IBD is understudied, and the underlying molecular mechanisms remain unknown. In this study, colonization of Il10-deficient mice with Alistipes timonensis DSM 27924 delays colitis development. Colonization does not significantly alter the gut microbiome composition, but instead shifts the host plasma lipidome, increasing phosphatidic acids while decreasing triglycerides. Outer membrane vesicles (OMVs) derived from Alistipes are detected in the plasma of colonized mice, carrying potentially immunomodulatory metabolites into the …

Lighting Up The Cell: Developing A Luminescent Lanthanide Probe For Detecting Rnas, Jonathan Savell

Honors Projects

An anion detecting luminescent probe, Tb:DO2A-Cs124, was repurposed for use in RNA imaging. Potential RNA aptamers were identified for the molecule using Capture-SELEX and MinION sequencing. Fluorimetry data revealed these aptamers did not allow for the probe to luminesce in the presence of target RNAs due to adenosine monophosphate’s ability to quench the emission signal.

Refinement And Application Of The Absorption Cross-Section Of Molecular Bromine With Relevance To Atmospheric Chemistry, Callum Flowerday, Ryan Thalman, Jaron C. Hansen, Eric T. Sevy, Jason J. Sorensen, Matthew C. Asplund

ScholarsArchive Data

Defined Br2 XS - is the defined absorption cross-section using the UVvis spectrophotometer.

BBCEAS - This is raw absorption data measured using the BBCEAS (see article for details).

UVvis raw - This is the raw absorption data measured using the UVvis spectrophotometer.

A Hormone-Dependent Trna Half Promotes Cell Cycle Progression Via Destabilization Of P21 Mrna, Takuya Kawamura, Megumi Shigematsu, Yohei Kirino

Department of Biochemistry and Molecular Biology Faculty Papers

tRNA halves are among the most abundant short non-coding RNAs in the cellular transcriptome. Here we report that in androgen receptor-positive LNCaP prostate cancer cells, the hormone-dependent 5'-tRNALysCUU half promoted cell proliferation by facilitating cell cycle progression. Global mRNA profiling upon the 5'-tRNALysCUU half depletion revealed that the mRNA of p21, a negative regulator of the cell cycle, is post-transcriptionally destabilized via a 5'-tRNALysCUU half-driven mechanism. YBX1, identified as a protein interacting with 5'-tRNALysCUU half in the cytosol, was shown to stabilize p21 mRNA. Specific sequences resembling the 5'-tRNALysCUU half, located in the 3'-UTR of p21 mRNA and termed LL588, …

A Novel Approach To Treat Trastuzumab Resistant Her2+ Breast Cancer: Activation Pkcδ, Maria Grazia Mejia Monroy

Master's Theses

In the United States, approximately one in eight women will be diagnosed with invasive breast cancer in her lifetime and one in forty will die from breast cancer. From among all the different subtypes of breast cancer, HER2+ can be found in approximately 20% of breast cancer tumors. HER2 overexpression has been associated with an aggressive form of breast cancer, increasing the risk of metastasis or recurrent tumors in 50% of patients. The standard of care for HER2 positive breast cancer, trastuzumab, has been effective for some patients; however, others develop resistance over time, leading to disease progression and metastasis. …

Pyruvate Dehydrogenase Kinase 4 Mediates Sex Specific Outcomes In Sepsis Induced Cardiomyopathy, John Yap

Dissertations

During sepsis, males often experience worse cardiac outcomes than females. Here, we identified pyruvate dehydrogenase kinase 4 (PDK4) as a key contributor to this disparity. PDK4 is a mitochondrial protein that regulates glucose utilization by inhibiting pyruvate dehydrogenase (PDH). Using a mouse model of endotoxemia, we induced acute inflammation with a sublethal dose of lipopolysaccharide (LPS), which caused cardiac dysfunction and significantly increased myocardial PDK4 expression in males but not females. Cardiac-specific PDK4 overexpression promoted LPS-induced cardiac dysfunction in both sexes, whereas cardiac-specific PDK4 knockout provided protection. In wild-type males, LPS disrupted cardiac metabolism by decreasing PDH activity and fatty …

Breaking The Rules: Post-Translational Modifications And Proteome Dynamics During Anoxia, Chelsea Jordan Hughes

Dissertations and Theses

Most organisms are ill-equipped to survive anoxia, but some organisms have developed molecular strategies to mitigate the cellular stressors associated with a lack of oxygen. While it is established that anoxic survival is contingent on metabolic suppression, it is unclear what mechanisms support this change in gene expression. Gene expression is regulated by a variety of mechanisms within the cell, including alteration of chromatin structure through histone modifications and protein modifications which contribute to the ever-changing proteomic landscape of the cell. Protein modifications such as ubiquitylation can lead to the degradation of proteins, while modifications to transcription factors can change …

United Seas For Resilient Reefs: A Blueprint For Coral Conservation Through International Cooperation, John J. Bohorquez, Maoz Fine, Dana I. Grieco, David A. Gill, Ali Al-Swalimih, Jacqueline Padilla-Gamino, Isaiah W. Bolden, Margaux Hein, Callum Backstrom, Melanie Mcfield, Raphael Martinez, Benjamin Midberry, Fahd Al-Guthmy, Ellen K. Pikitch, Natalia Benejam, Chen Azulay, Britt Ronen, Oren Levy, Anne Mcelroy, Karine Kleinhaus

School of Marine & Atmospheric Sciences Faculty Publications

Coral reefs are one of Earth’s most vital and threatened ecosystems. They protect coastlines, generate billions of dollars of tourism revenue, support valuable fisheries, and contribute to the development of vital medicines. Yet half of the world's coral reefs have been lost in the last 50 years, and 90% of remaining reefs are projected to die off by the middle of this century, mainly due to warming seas from climate change.

Despite these challenges there is reason for hope. Some coral reefs – such as in the northern Red Sea and Gulf of Aqaba – have demonstrated remarkable resilience to …